The Biocides Business Edited by D. J. Knight and M. Cooke
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9
The Biocides Business Regulation, Safety and Applications
Edited by Derek J. Knight and Mel Cooke
The Editors of this Volume
Dr. Derek J. Knight SafePharm Laboratories LTD Shardlow Business Park London Road Derbyshire Derby DE72 2GD U.K. Dr. Mel Cooke Alchemy Compliance LTD 2 Harvey Close Ruddington Nottinghamshire NG 11 6 N3 U.K.
This book was carefully produced. Nevertheless, editors, authors and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No.: Applied for. British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library. Die Deutsche Bibliothek – CIP Cataloguing-in-Publication Data: A catalogue record for this publication is available from Die Deutsche Bibliothek. ª Wiley-VCH Verlag GmbH, Weinheim 2002 All rights reserved (including those of translation in other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into machine language without written permission from the publishers. In this publication, even without specific indication, use of registered names, trademarks, etc., and reference to patents or utility models does not imply that such names or any such information are exempt from the relevant protective laws and regulations and, therefore, free for general use, nor does mention of suppliers or of particular commercial products constitute endorsement or recommendation for use. Printed on acid-free paper. Printed in the Federal Republic of Germany.
Cover Illustration The image used (herein) was obtained from IMSI’s Master Photos Collection, 1895 Francisco Blvd. East, San Rafael, CA 94901-5506, USA
Composition Mitterweger & Partner Kommunikationsgesellschaft mbH, Plankstadt Printing Strauss Offsetdruck GmbH, Mo¨rlenbach Bookbinding Großbuchbinderei J. Scha¨ffer GmbH & Co. KG, Gru¨nstadt ISBN 3-527-30366-9
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Contents Preface XV Editors and Authors
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1
The Political, Social, and Economic Framework
1.1 1.2 1.3 1.4 1.5
Aynsley Kellow Introduction 1 Historical, Cultural, and Economic Influences 3 National and International Regulation 6 International Organizations and Chemicals 16 Conclusion 23
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2.1 2.1.1 2.2 2.3 2.4 2.4.1 2.4.2 2.4.3 2.5 2.6 2.6.1 2.6.2 2.7 2.8
The Biocides Market
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Patricia Martin Introduction 27 EC Market: End-use Applications 29 EC Market: Consumption of Biocidal Products by End Use Global Market: Consumption of Biocidal Products by Geographical Region 31 Supply Chain for Biocidal Products 32 Active-ingredient Manufacturers 32 Formulators/Service Companies 33 Distributors 34 Key Drivers for Market Development 34 History and Current Trends 36 European Community 36 United States of America 39 Impact of New Legislation 40 Conclusions 43
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Regulatory Control of Biocides in Europe
3.1 3.2
Derek J. Knight and Mel Cooke Introduction 45 The EU Biocidal Products Directive
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The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9
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3.2.1 3.2.2 3.2.3 3.2.4 3.2.5 3.3 3.4 3.4.1 3.4.2 3.4.3 3.5 3.5.1 3.5.2 3.5.3 3.5.4 3.5.5 3.5.5.1 3.5.5.2 3.5.5.3 3.6
History and Development 46 Scope of the Biocidal Products Directive 47 Approval Systems 49 Data Requirements 50 Risk Assessment and the Common Principles for the Evaluation of Dossiers 53 The Review Program for Existing Biocide Active Substances and Biocidal Products 56 European Union Chemical Control Measures 59 Scope of European Union Legislation 59 European Union Chemicals Legislation 60 Other European Controls Affecting Biocides 62 National European Biocide Authorization Schemes 63 Introduction 63 The Netherlands 64 Belgium 67 The United Kingdom 67 Scandinavia 70 Denmark 70 Finland 70 Sweden 70 Conclusion 71
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Regulation of Biocides in the United States
4.1 4.1.1 4.1.2 4.1.3 4.2 4.2.1 4.2.2 4.3 4.3.1 4.3.1.1 4.3.1.2 4.3.2 4.3.2.1 4.3.2.2 4.3.2.3 4.3.2.4 4.3.3 4.3.4 4.4 4.4.1
Sue Crescenzi Introduction to Pesticide Regulation in the United States 75 Legal Authority 75 Federal Agencies with Responsibility for the Regulation of Biocides Information Resources 77 Regulation of Biocides in the United States 77 Regulation of Biocides Generally 77 Regulation of Antimicrobial Biocides 77 Registration of a New Active Ingredient 80 Active Ingredient Data Requirements 80 Antimicrobial Active Ingredient Data Requirements 81 Follow-on Registration of an Active Ingredient 82 Registration of End-use Product Formulations 82 Formulated Products Entitled to Formulator’s Exemption 82 Formulated Products Not Entitled to Formulator’s Exemption 82 Product-specific Data 83 Applications for Formulated Product Me-too Registrations 83 Amendments to Change Existing Registrations 83 Changes Not Requiring Amendments 84 Regulation of Biocides Used in, on, or in Contact with Food 84 EPA Regulation of Pesticide Chemicals in or on Food 84
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4.4.2 4.4.3 4.4.4 4.4.5 4.5 4.5.1 4.5.2 4.5.3 4.6 4.6.1 4.6.2 4.6.3 4.6.4 4.6.5 4.7 4.8 4.8.1 4.8.2 4.8.3 4.9 4.10 4.11 4.12 5
5.1 5.2 5.2.1 5.2.1.1 5.2.1.2 5.2.1.3 5.2.1.4 5.2.2 5.2.3 5.2.4 5.2.5 5.3 5.3.1 5.3.1.1 5.3.2
FDA Regulation of Food Additives 85 FDA Regulation of Food-contact Substances 85 Overlapping EPA and FDA Jurisdiction for Antimicrobial Food-Contact Uses 85 EPA Identification of Biocides as Food Contact 87 Pesticide Re-registration 88 Expedited Re-registration 88 Tolerance Reassessment 88 Fifteen Year Registration Review 89 Data Protection and Data Compensation Procedures 89 Procedures for Compliance with Data Protection and Compensation Requirements 90 Compensation Offers and Arbitration 91 EPA’s Role in Data Compensation 92 Data Call-ins and Offers to Jointly Develop Data 92 Data Protection and Compensability under FFDCA for Active and Inert Ingredients 93 EPA Regulation of Pesticide Inert Ingredients 93 Registrants’ Continuing Obligations 94 Data Call-ins 94 Reporting Adverse Effects Information 95 Other Reporting and Recordkeeping Requirements 96 Pesticide Import and Export Requirements 96 Cancellation and Suspension 97 EPA Enforcement Authority 98 Pesticide Licensing in Individual States 98 Regulatory Control of Biocides in Other Countries
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Sara Kirkham and Mel Cooke Introduction 103 Japan 104 Chemical Substances Control Law 104 The Inventory of Existing Substances 105 Exemptions from Notification 107 Standard Notification 108 Class I and II Specified and Designated Substances 110 The Ministry of Health, Labor, and Welfare Industrial Safety and Health Law 111 Hazard Communication 113 Other Chemical Legislation 113 Summary 115 Korea 115 The Toxic Chemicals Control Law and Ministry of Environment 115 Notification Requirements 116 Ministry of Labor Toxicity Examination 119
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5.4 5.4.1 5.4.2 5.5 5.6 5.6.1 5.6.2 5.6.3 5.7 5.7.1 5.7.2 5.8 5.8.1 5.8.2 5.8.3 5.9 5.10 5.11 5.12 5.13 5.14
China 120 Biocide Products for Pest Control (BPPC) 120 Disinfectants and General Biocidal Products (DGBP) 120 Philippines 122 Australia 124 NICNAS 124 Biocides Not Covered by NICNAS 126 Conclusion 128 New Zealand 128 Toxic Substances Act and the HSNO Act 128 Arrangements for Biocides Classified as Pesticides 130 Canada 131 Food and Drugs Act 133 Pest Control Products Act 134 Canadian Environmental Protection Act 134 Switzerland 135 South Africa 137 South America 138 India 138 Slovenia 138 Conclusion 139
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Human Health, Safety, and Risk Assessment
6.1 6.2 6.2.1 6.2.2 6.2.2.1 6.2.2.2 6.2.2.3 6.2.2.4 6.2.2.5 6.2.2.6 6.2.2.7 6.2.2.8 6.2.2.9 6.2.3 6.3 6.3.1 6.3.2 6.3.3 6.4 6.4.1 6.4.2
Roland Solecki What Is Risk Assessment? 141 Hazard Identification and Assessment 144 Information Gathering 144 Hazard Identification 146 Acute Toxic Effects 146 Irritation, Corrosivity, and Sensitization 147 Toxicokinetics and Metabolism 147 Repeated Dose Toxicity 148 Genotoxicity 149 Carcinogenicity 149 Reproductive Toxicity 150 Special Effects 150 Medical and Other Human Data 151 Dose-Response Assessment 152 Exposure Assessment 153 Characteristics of Human Exposure 153 Occupational Exposure 154 Consumer Exposure 156 Risk Characterization 157 Threshold Exposure Levels 157 Safety Margins 158
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6.4.3 6.5 6.5.1 6.5.2 6.6
Benchmark Concepts 159 Regulatory Decision-making 161 Decisions for Active Substances 161 Decisions for Products 162 Conclusions 164
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Environmental Safety and Risk Assessment
7.1 7.1.1 7.1.2 7.1.3 7.2 7.2.1 7.2.2 7.2.2.1 7.2.2.2 7.2.3 7.2.3.1 7.2.3.2 7.2.3.3 7.3 7.3.1 7.3.1.1 7.3.1.2 7.3.1.3 7.3.2 7.4 7.4.1 7.4.2 7.4.3 7.4.3.1 7.4.3.2 7.4.4
Robert Diderich What Is Risk Assessment? 167 Introduction 167 Definitions and Process 168 Risk Assessment and Data Requirements 169 Exposure Assessment 169 Release Estimation 171 Environmental Behavior 174 Transport within or between Compartments 174 Transformation and Degradation Processes 177 Environmental Concentrations 180 Surface Water and Sediment 180 The Atmosphere 182 Soil 182 Effects Assessment 184 Uncertainty Factors for Establishing PNECs 184 The Aquatic Ecosystem 185 The Sediment 186 The Terrestrial Ecosystem 186 The Statistical Extrapolation Method 187 Regulatory Decision-making 188 Risk Characterization 188 Risk Assessment of Biocidal Products 189 Other Criteria 191 Persistence, Bioaccumulation, and Toxicity 191 Comparative Assessment 192 Conclusion 192
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8.1 8.2 8.2.1 8.2.2 8.2.3 8.2.4 8.3
Wood Preservatives
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David Aston Introduction 197 Biological Degradation 197 Microbial Degradation of Timber 198 Insects and the Degradation of Timber 199 Termites and the Degradation of Timber 199 Degradation of Timber in the Marine, Brackish, and Freshwater Environments 199 Wood Preservatives-Some Characteristics 200
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8.3.1 8.3.2 8.3.3 8.4 8.5 8.5.1 8.5.2 8.5.3 8.5.4 8.5.5 8.5.6 8.5.7 8.5.8 8.6 8.7 8.8 8.9 8.9.1 8.9.1.1 8.9.1.2 8.9.2 8.10 8.10.1 8.10.2 8.10.3 8.10.4 8.10.5 8.10.6 8.11 8.11.1 8.11.2 8.11.3 8.11.4 8.12 8.13 8.14 8.14.1 8.14.2 8.15 8.16
Categorization by Function 200 Regulation of Wood Preservatives 200 Desirable Characteristics of Wood Preservatives 201 Wood Preservation at Various Stages of the Timber Transformation Process 201 Deciding on the Degree of Protection Needed 201 The Proposed End Use for the Wood Product 202 The Geographical Location in Which It Is Intended To Be Used 202 The Expected Service Life or Degree of Protection Required 202 Structural or Nonstructural Applications 202 Ease and Economics of Replacement 203 Service Factors 203 Biological Hazard Classes 203 Use Classes 204 Selection and Specification of Preventive Preservative Treatments 206 Selection and Specification of Curative Preservative Treatments 207 Wood Durability and Treatability 207 Methods of Applying Wood Preservatives 208 Treatments for Seasoned Wood 208 Pressure Treatments 208 Nonpressure Methods 209 Treatments for Unseasoned Timber 210 Types of Wood Preservatives 210 Introduction 210 Industrial Wood Preservatives 211 Remedial (Professional), Curative and Preventive Wood Preservatives 213 Amateur/Do It Yourself Wood Preservatives 213 Listing of Active Substances Currently Registered for Use in Wood Preservatives in the UK 214 European Chemicals Bureau 214 Wood Preservative Systems 215 Introduction 215 Industrial 215 Remedial 216 Amateur 216 Usage Rates 216 Disposal of Wood Commodities Containing Treated Wood and Environmental Risk 217 Mechanisms of Action 218 Microbiocides 218 Insecticides 220 Efficacy Assessment of Wood Preservatives 222 Looking Ahead 223
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Slimicides
9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.7.1
Ian Gould and James Hingston Microbiological Problems Associated with the Papermaking Process Bacteria 226 Fungi 227 Algae 229 Cooling Towers 229 Control of Microbial Slimes and Deposits 230 Biocides and Their Activity 230 Examples of Biocidal Active Ingredients 231
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General Purpose Preservatives
10.1 10.2 10.3 10.3.1 10.3.2 10.3.3 10.3.4 10.3.5 10.3.6 10.3.7 10.3.8 10.3.9 10.3.10 10.3.11 10.3.12 10.3.13 10.3.14 10.3.15 10.4
Richard Elsmore Introduction 233 Biocide Selection 234 Biocide/Preservative Application Areas 235 Cooling Water Biocides 235 Cosmetic and Pharmaceutical Preservation 236 Constructional Material Preservation 237 Detergent and Household Product Preservation 238 Food Preservation 239 Fuel Preservation 240 Leather Preservation 241 Metalworking Fluid Preservation 242 Oil and Gas Exploration and Recovery 242 Plastic Preservation 243 Polymer Emulsion and Adhesive Preservation 243 Surface Coating Preservation 244 Swimming Pool and Spa Treatments 245 Textile Preservation 246 Miscellaneous Uses 246 Conclusion 247
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Disinfectants and Public Health Biocides
11.1 11.1.1 11.1.2 11.2 11.2.1 11.2.2 11.2.3 11.2.3.1 11.2.3.2 11.2.3.3
Kerys Mullen Introduction 251 Microorganisms – An Overview 251 Harmful and Nonharmful Organisms Disinfection and Disinfectants 253 Disinfection Procedure 253 Designing a Disinfectant 254 Types of Disinfectant Agents 255 Acids 255 Alkalies 255 Alcohols 255
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11.2.3.4 11.2.3.5 11.2.3.6 11.2.3.7 11.2.3.8 11.2.3.9 11.2.3.10 11.2.3.11 11.3 11.3.1 11.3.1.1 11.3.1.2 11.3.1.3 11.3.2 11.3.2.1 11.3.2.2 11.3.2.3 11.3.3 11.3.3.1 11.3.3.2 11.3.3.3 11.4 11.4.1 11.4.2 11.4.3 11.4.4 11.5
Aldehydes 255 Biguanides 255 Chlorine Active Compounds 256 Iodophores 256 Phenolic Disinfectants 256 Peroxygen Disinfectants 257 Quaternary Ammonium Compounds (QACs) 257 Amphoterics 258 Detailed Examples of Disinfectants 258 Hydrogen Peroxide 258 Mode of Action 258 Factors Affecting Performance 258 Applications 259 Quaternary Ammonium Compounds 259 Mode of Action 259 Factors Affecting Performance 260 Applications 260 Sodium Hypochlorite 261 Mode of Action 261 Factors Affecting Performance 262 Applications 262 Efficacy of a Disinfectant 264 Phase I – Biocidal Activity 264 Phase II – In-use Testing 264 Phase III – Consumer Test 264 Issues with Testing 265 Concluding Remarks 265
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Rodenticides and Insecticides
12.1 12.2 12.2.1 12.2.2 12.2.3 12.3 12.3.1 12.3.2 12.3.3 12.4 12.4.1 12.4.2 12.4.3 12.5
Alan Buckle Introduction 267 The Market for Rodenticides and Insecticides as Biocides 268 Consumer Retail Market 268 Professional Pest Management (PPM) Market 269 Municipal Market 270 Rodenticides 271 Rodenticide compounds 271 Formulations 272 Methods of Application and Patterns of Use 273 Insecticides 276 Insecticide Compounds 276 Formulations 279 Methods of Application, Equipment, and Patterns of Use 282 Conclusions 284
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13.1. 13.2 13.3 13.4 13.4.1 13.4.2 13.4.3 13.4.4 13.5 13.5.1 13.5.2 13.5.3 13.5.3.1 13.5.3.2 13.5.3.3 13.5.3.4 13.5.4 13.5.4.1 13.5.4.2 13.5.4.3 13.5.4.4 13.6 13.6.1 13.6.2 13.6.3 13.6.4 13.7
Antifoulants and Marine Biocides
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Carol Mackie and Graham Lloyd Introduction 287 Uses for Antifoulants 288 What Type of Organisms Are Found 288 Types of Antifoulant Used on Ships 288 Soluble Matrix 289 Insoluble Matrix 289 TBT Self Polishing Copolymer 289 Ablative (Polishing Copolymer) Tin-free 289 Active Substances Used in Antifouling Paints 289 Copper and Copper Salts 290 Tributyl Tin Oxide 292 Booster Biocides 293 4,5-Dichloro-2-n-octyl-isothiazolin-3-one (DCOI) 293 Zinc and Copper Pyrithione 293 4-tert-Butylamino-2-methylthio-6-cyclopropylaminotriazine 294 N-(Dichlorofluoromethylthio)-N,N’-dimethyl-N’-phenylsulfamide 295 Nonchemical Alternatives 295 Silicone Elastomers 295 Fibers 295 Enzymes 296 Aluminum Silicate 296 Data Requirements 296 Data Requirements for an Active Substance According to the EU Biocidal Products Directive 296 Data Requirements for Antifouling Paint 298 Leach Rates 298 Exposure Assessments and Emission Scenarios 299 What for the Future 299 Annex Directive 98/8/EC of the European Parliament and of the Council of 16 February 1998 concerning the placing of biocidal products on the market 301 Index
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Preface Why this book?
Biocides are disparate groups of chemicals often referred to as nonagricultural pesticides. The European Biocidal Products Directive (BPD) has honed this definition and given an identity to biocidal products and the industry that supplies them. Manufacturers and formulators need to combine their efforts to ensure a continued supply of their products. This new coherence has provided the impetus for us to bring together eminent professionals from industry, national authorities, and specialist consultancies to discuss issues important to them. The Biocides Business will enable the reader to get a blanced, up-to-date overview of biocides, from the commercial and technical aspects to worldwide regulatory compliance.
The Biocides Market
The worldwide biocides market has an annual sales value of up to £ 3 billion, with a growth rate currently of ca. 4 % per annum. The major user is North America, followed by Europe then Japan. The consumption is fairly evenly split between the many product types. Within the EU, the demand for industrial biocides is led by Germany, followed by the UK, France, and Scandinavia, then Italy and the Benelux region. Biocide active substances are around 12 % of the global value of all pesticides at the manufacturer level (the remainder of the sales being for agricultural and garden plant protection products). The biocides industry involves a highly varied assortment of mainly small- and medium-sized businesses. The industry delivers its final products to the end user by a complex supply and manufacture chain. Many active substances are used both in plant protection products and in biocidal products, so the leading pesticide companies are involved in the manufacture of the active ingredient for both types of product. The European BPD is the toughest legislation that the biocide industry has had to face and could cost the industry over £ 340 million to comply with. The costs are too high to maintain the existing range of products, and some products, particularly those in niche markets, will no longer be viable. Many businesses will merge or disappear completely. Manufacturers, distributors, and users of biocidal products will suffer in the new regulatory climate. Dr. Patricia Martin, the principal consultant at Product The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9
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Assessment and Regulatory Compliance, draws on her extensive experience to describe the biocides market in Chapter 2.
Control of Biocides
Different regulatory jurisdictions (EU, USA, and Japan) have different definitions for biocides and varying requirements for their registration (the process which a product must undergo to be allowed to be sold). For example, some countries consider disinfectants and sanitizers as biocides, but in others they are medicines or general chemicals. As a result, the regulatory pattern is complex, with many countries having split responsibilities between different regulatory bodies for different biocide product types. This can result in barriers to trade, increased costs, and differing levels of protection of humans and the environment. Until 14 May 2000 when the BPD came info force, the European market was fragmented, with different regulatory requirements in different EU Member States. Some countries, notably Germany, had few specific control measures, and biocides were covered by the general EU chemicals legislation. Others, such as the Netherlands, had their own vigorous national approval schemes, requiring extensive testing. In the EU, the Biocidal Products Directive will gradually supersede the various current national schemes and harmonize the requirements for the registration of biocidal active ingredients and their formulations. There is also a 10-year review program to evaluate existing active substances and require authorization of formulated biocidal products containing them. The current state of the BPD is discussed in detail in Chapter 3 by Dr. Derek J. Knight of Safepharm Laboratories Ltd. and Dr. Mel Cooke of Alchemy Compliance, who was formerly at Safepharm Laboratories. Although the European Biocidal Products Directive has been a driving force in recent developments in the industry, we have taken a truly global approach, and have provided detailed information on all major economic jurisdictions. In the USA, biocides are not defined in statute, but many such products are covered by the same regulations as agricultural pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). With the passage of the Food Quality Protection Act (FQPA) in 1996, registration of antimicrobial pesticides in the USA has become more complex. The act stipulates that any pesticide, including antimicrobials, will cause no unreasonable adverse effect on man or the environment, but also that the pesticide is safe for sensitive subpopulations, such as infants and children. Furthermore, the risk assessment also takes into account the effect of active substances with a comparable mode of action. The effect of the US FQPA, as with the European ideal of comparative assessment, is that applications for competitive products may interfere with each other in the authorization procedure and decision making. Dr. Sue Crescenzi of Steptoe and Johnson provides critical analysis of the situation in the USA in Chapter 4. The global regulatory picture is completed in Chapter 5 by Dr. Sara J. Kirkham of Safepharm Laboratories and Dr. Mel Cooke, with emphasis on the key markets of Japan, Korea, China, the Philippines, Australia, New Zealand, Canada, and Switzerland, but also covering other markets with defined chemical control regulations.
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Safety and Regulation of Biocides
Biocides are intended to be toxic, but only to the target organisms to be controlled. Such biologically active chemicals could potentially pose a risk to humans or the environment. Hence biocides are one of the most tightly regulated and controlled type of chemical product. The risk from a biocide is determined from its hazardous properties and the likely exposure of humans and the environment throughout its life cycle. The intrinsic chemical, health, and environmental hazardous properties for the hazard assessment are largely determined by standardized laboratory studies, although other means of estimating and predicting hazardous properties may sometimes be used. Such an in-depth science-based risk assessment will give a realistic estimation of the potential impact of a biocide. However, this is time- and resource-consuming process that can delay regulatory approval, and such delays can be costly to industry. Dr. Roland Solecki of the German Health Ministry shows how such risk assessments are conducted relating to the impact of biocides on human health (Chapter 6), while Robert Diderich of the French Environment Ministry discusses risk assessment relating to environmental safety (Chapter 7). Both authors use the EU risk assessment procedure to illustrate the general principles of safety assessment for regulatory decision-making and product approvals. Professor Aynsley Kellow of the University of Tasmania sets the scene for the book in Chapter 1 by placing biocides and their regulation and controls within a global political and socio-economic context, and discusses the public attitude to risks from biocides.
What Biocides Are and How They Are Used
Wherever there is a source of nutrition and moisture, micro-organisms and other pests will grow, even in extreme climatic conditions. Indeed, recent evidence suggests that microbial cells are found in outer space. These organisms may damage our health, our food, and our economy. The second part of The Biocides Business provides a broad overview of their main uses as disinfectants, preservatives, and pest controls. Each sector faces particular commercial and regulatory challenges. Some will see familiar registration schemes changed beyond recognition, while others will be facing for the first time rigorous regulatory control. Specialist contributors describe the chemistry, formulation, use, and specialized hazard testing for each type of biocide, and outline the important issues they are facing. Biocidal products are preparations, containing one or more active substances, that control such harmful organisms by chemical or biological means. They protect health, improve product performance, and prevent spoilage, and are increasingly important to modern life in ensuring safe, long-lasting, and effective products. Biocides encompass a wide range of applications including disinfection, preservation, and pest control. Households consume ever-increasing amounts of biocides. The assault on bacteria in the household has fuelled great interest in antibacterial products. Common household cleaners can contain simple inorganic chemicals such as sodium hypochlorite or
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hydrochloric acid. Chlorine-releasing biocides also have industrial applications in swimming pools and spas, which are prone to fouling from slime and microbe-induced corrosion. Disinfectants and public health biocides are described by Kerys Mullen of Lever Brothers Ltd. in Chapter 11. There is no doubt that the demand for biocidal products will continue to grow as the public and consumers’ awareness of the benefits of continued improvements in hygiene becomes ever more apparent. It is up to the biocides industry to developed these highly desirable products against a background of increasingly stringent legislative measures, and this will surely require openness and co-operation with other sectors of the supply chain. Related to disinfection, where the desired effect is to control a broad spectrum of micro-organisms, is preservation, where it may be sufficient to inhibit the growth of micro-organisms to prevent spoilage. Dr. Richard Elsmore of Warwick International Ltd. addresses the broad subject of general purpose preservatives in Chapter 10, covering diverse application areas such as cosmetics, food, fuel, metalworking fuels, and polymers. Wood preservatives are of enormous economic importance and are the dominant use for biocides in the EU. They include a wide range of pest control from moulds to insects in a variety of circumstances. Recently, some wood preservatives have been scrutinized because they contain heavy metals or volatile organic substances. Dr. David Aston of Arch Timber Protection discusses these issues and others in Chapter 8. Micro-organisms may interfere with manufacturing processes by causing rot or slimes to form, blocking valves and pipes, or corroding steel, plastic, and rubber. Slimicides are important in many industrial applications, as described by Ian Gould of BetzDearborn Ltd. and James Hingston of Safepharm Laboratory Ltd. in Chapter 9. The specialist area of antifouling biocides is the subject of intense debate. These products have environmental benefits in reducing fuel consumption on ships by reducing drag, but some have become notorious marine pollutants, specifically due to their ability to affect the endocrine system of some wildlife species. Dr. Graham Lloyd of Steptoe and Johnson and Dr. Carol Mackie of Compliance Services International discuss antifouling products and marine biocides in Chapter 13. Dr. Alan Buckle of Syngenta is the author of Chapter 12 on rodenticides, insecticides, and pest control agents. The control of higher order pests raises particular concerns for nontarget species, particularly wildlife and humans. The mode of action is also important as the biocide is expected to cause no undue suffering of the target species itself. We hope this book will allow our readers to appreciate the diversity of biocides, how they benefit modern life, and understand the measures taken to make sure they are safe to use. The Editors wish to acknowledge and thank the following people who have helped in the preparation for this book: Karin Sora of Wiley-VCH for advice and the invitation to edit this book; Safepharm Laboratories’ Board of Directors for permitting us the time and resources to make this book possible; Jacqueline Billing and Sara Kirkham of Safepharm Laboratories for much of the co-ordination and administration; other Safepharm staff, in particular Sheila Stokoe for word processing and Michael Andrew for editorial comments on Chapter 3, and several colleagues who gave initial advice and
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suggestions; those who provided references when we first assessed the viability of the book, in particular Christina Jackson, whose suggestions led to the title of the book; and finally we give our sincere thanks to the authors, particularly those that stepped in close to the deadline, for their time, effort, and generosity in sharing their valuable expertise. Derek Knight and Mel Cooke
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Editors and Authors
Editors Dr. Derek J. Knight SafePharm Laboratories Limited PO Box 45 Derby DE1 2BT U.K. (Preface, Regulatory Control of Biocides in Europe)
Derek J. Knight is the Director of Regulatory Affairs at Safepharm Laboratories Ltd, a leading UK contract research organization specializing in safety assessment of chemicals, biocides, and agrochemical pesticides. He heads a team of regulatory affairs professionals who deal with a wide range of registration projects covering many product types for regulatory compliance in all the key markets globally. As such he has gained an overall perspective into commercial issues associated with the regulation of the biocides and chemical industry. His doctoral studies at the University of Oxford were in organosulfur chemistry.
Dr. A. Mel Cooke Alchemy Compliance Ltd. 2 Harvey Close Ruddington Nottinghamshire NG 11 6 N3 U.K. Formerly of SafePharm Laboratories Limited (Preface, Regulatory Control of Biocides in Europe and Regulatory Control of Biocides in Other Countries)
Mel A. Cooke is the founder of Alchemy Compliance Ltd. and offers independent advice on compliance issues, especially relating to biocides, notification of new chemicals, and existing chemicals programs. He gained over six years of regulatory experience at Safepharm Laboratories, reaching the position of Deputy Head of Registration Services. He has previously worked in Cambridge and Stuttgart as an editor of research journals, and gained industrial experience in the Ciba-Geigy laboratories in Basel. He researched the synthetic organic chemistry and pharmacology of inositol phosphates to gain his PhD from the University of Leicester.
Authors Dr. David Aston Arch Timber Protection Ltd. Technical Centre Wheldon Centre Castleford WF10 2JT U.K. (Wood Preservatives)
David Aston has 27 years experience in the wood preservation industry. During that time he has held technical, sales and marketing, and environmental positions in his company (formerly known as Hickson Timber Products and now as Arch Timber Protection). He has been active in the development of national and European standards and represents both his company and the industry in the interface between the regulators and industry in technical, health and safety, and environmental matters. He is currently President of the European Wood Preservative Manufacturers Group.
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN: 3-527-30366-9
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Editors and Authors Dr. Alan Buckle Syngenta Fernhurst Hazelmere Surrey GU27 3JE U.K. (Rodenticides and Insecticides)
Alan Buckle is Global Technical Manager for the Public Health business of Syngenta, having fulfilled similar roles in the ICI and Zeneca legacy companies. Prior to joining ICI in 1985, he held posts as a research scientist with the UK Ministry of Agriculture, Fisheries and Food, the Centre for Overseas Pest Control (now the Tropical Products Institute), and the Overseas Development Administration, during which time he completed many overseas projects and assignments for international agencies.
Dr. Sue Crescenzi Technical Specialist Environment, Health and Safety Steptoe and Johnson 1330 Connecticut Avenue, NW Washington DC 20036–1795 USA (Regulatory Control of Biocides in the United States)
Sue Crescenzi is a nonattorney regulatory specialist at Steptoe and Johnson, with almost 20 years experience in pesticide registration and regulation. She heads the firm’s pesticide registration consulting practice, working closely with clients and EPA staff on registration actions and policy issues, with an emphasis on antimicrobials. Dr. Crescenzi also assists clients in developing and presenting training programs to bring pesticide registration and compliance functions in-house. She has worked closely with the EPA on the development and implementation of a number of pesticide regulatory proposals, both individually and as a participant of industry coalitions. For example, she has worked with the EPA on tiered data requirements for antimicrobial pesticides and guidance to registrants on compliance with expanded reporting requirements on pesticide adverse effects.
Robert Diderich Institut National de l’Environnement Industriel et des Risques (INERIS) B.P. 2 60550 Verneil en Halatte France (Environmental Safety and Risk Assessment)
Robert Diderich has been involved in environmental risk assessment of chemical substances since 1992, when he joined the German Federal Environmental Agency. He has been working in France since 1995, first at the Ministry of the Environment and then at the National Institute for Industrial Environment and Risks (INERIS), where he is currently studies the environmental risks of industrial chemicals as well as biocides. He is involved in the continuous development of the EU technical guidance documents for the environmental risk assessment of industrial substances as well as biocidal substances.
Dr. Richard Elsmore Warwick International Ltd Mostyn Holywell Flintshire CH8 9HE U.K. (General Purpose Preservatives)
Richard Elsmore of Warwick International Limited has worked in the biocides industry since 1984 and has been involved with a wide range of both application areas and product chemistries. He has worked for biocidal active ingredient manufacturers and biocidal product formulators including Boots Microcheck, Coalite Chemicals, Great Lakes Water Treatment, and Robert McBride Ltd. before joining Warwick International Ltd. During this time he has been responsible for technical and regulatory management and for the marketing of biocides on a global basis. He has been responsible for the introduction of several of the commonly used biocides that are currently on the market. He holds a BSc and Doctorate in Microbiology from Cardiff University and an MBA from the University of Nottingham. He lives in North Wales with his wife Caroline, twins Morgan and Rhiannon, and an assortment of cats, dogs, and chickens.
Editors and Authors Ian Gould Business Manager Europe Microbiological Control Pulp and Paper Division BetzDearborn Ltd. Foundry Lane Widnes Cheshire WA8 8DU U.K. (Slimicides)
Ian Gould graduated from The University of Salford in 1975 with a BSc Honours Degree in Applied Chemistry. Ian went on to work as a Scientist for Bowater Technical Services, then on to Ellesmere Port (part of Bowater U.K. Paper Company) working as a Process Technician and then Mill Chemist. Joining Betz in 1980 as a Sales Representative in the Paper Industry based in Kent, he went on to hold a variety of sales and technical positions in the UK Organisation, before becoming European Technology Manager for BetzDearborn. Following the acquisition of BetzDearborn by Hercules, Ian is now European Business Manager, Microbiological Control.
James Hingston SafePharm Laboratories Limited PO Box 45 Derby DE1 2BT U.K. (Slimicides)
James Hingston is currently working as a Registration Officer with SafePharm Laboratories Ltd, specializing in the approval of biocidal products. He has previously worked for the UK’s Health and Safety Executive in the Environmental Sciences Section of the Biocides and Pesticides Assessment Unit. He has also recently completed a PhD at Imperial College, London, researching the environmental effects of wood preservative biocides in aquatic environments.
Prof. Aynsley Kellow Head, School of Government University of Tasmania Box 252–22 GPO Hobart 7001 AUSTRALIA (The Political, Social and Economic Framework)
Aynsley Kellow is Professor of Government at the University of Tasmania. He specializes in environmental politics and policy and has published several books, including most recently Transforming Power and International Toxic Risk Management (both with Cambridge University Press). He is coeditor of Globalisation and the Environment (Edward Elgar) and has published papers in many journals, including Policy Studies Journal, Natural Resources Journal, International Political Science Review, and Political Studies.
Dr. Sara. J. Kirkham Senior Registration Officer Safepharm Laboratories Ltd PO Box 45 Derby DE1 2BT U.K. (Regulatory Control of Biocides in Other Countries)
Sara Kirkham obtained her PhD in bioinorganic chemistry researching synthetic methods of biomineralization. She began working at SafePharm Laboratories in Regulatory Affairs after completing her postgraduate studies. For the past two years she has been specializing in biocide and pesticide registration, and now leads the section of the Department of Registration Services dealing with these projects as Senior Registration Officer. She enjoys gardening, shopping, drinking wine, and travelling with her family.
Dr. Graham Lloyd Senior Regulatory Specialist Steptoe and Johnson 5 Telford Gardens Brewood Staffordshire ST19 9ED U.K. (Antifouling and Marine Biocides)
Graham Lloyd has been in the biocides industry for more than 20 years. He has a degree in Microbiology and worked for Unilever Research. Graham Lloyd then moved to Sterling Industrial as Technical manager. He was Regulatory Affairs manager at Albright & Wilson and Arch Chemicals. He is now Senior Regulatory Specialist with Steptoe and Johnson. He was Vice Chairman of the Cefic sector group, the European Producers of Antimicrobial Products (EPAS), and is now on the management committee of the European Biocidal Products Forum (EBPF). He is a member of the CEPE antifoulants working group, the Chemical Industry Association Biocides Sector Group, and various working groups associated with the BPD. He represented industry on the OECD Biocides Steering group and is an industry delegate at EU competent authority meetings.
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Editors and Authors Dr. Carol Mackie Principal Consultant Compliance Services International Pentlands Science Park Penicuik Nr. Edinburgh EH26 0PZ U.K. (Antifouling and Marine Biocides)
Carol Mackie has a PhD in Microbiology. She has been a consultant to the biocide industry for 5 years and is currently principal consultant and manager of Compliance Services International, European office. Previously she worked for the UK Health and Safety Executive, Pesticides Registration Section, where she was involved in the environmental risk assessment of nonagricultural pesticides. She is a member of the CEPE anti-fouling working group and CEFIC biocides shadow working group for ecotoxicity and environmental fate and is currently the CEPE/CEFIC biocides representative at the marine risk assessment technical sub-group meetings, organized by the European Chemicals Bureau.
Dr. Patricia Martin Product Assessment and Regulatory Compliance 37 Sydney Road Cradley Heath West Midlands B64 5BA U.K. (Biocides Market)
Patricia Martin holds a PhD in biochemical toxicology. Following her academic studies she spent some nine years working both at the University of Aston in Birmingham and then Birmingham University in the Institute of Occupational Health as a Research Fellow funded by among others the UK Health & Safety Executive. Her primary interest was occupational lung cancer. Studies included an international investigation of the bichromates industry, the possible role of synergistic interactions in the causation of lung cancer, and also the UK foundry industry. She joined Albright & Wilson in 1987 as their Company Toxicologist and for the next 14 years continued to represent the widely divergent product-related safety interests of the company in both UK and CEFIC Industry Groups. During this time, Patricia was Chairperson of the CEFIC Biocides Working Group on Toxicology and Data Waiving. With the takeover by Rhodia of Albright & Wilson Patricia seized the opportunity to branch out, and in 2001 she started her own consultancy business, Product Assessment and Regulatory Compliance. The consultancy is in its first year of operation, but already the clientele includes multinational companies, who, due to internal resource shortages, have a requirement for the practical experience of a seasoned toxicologist. Patricia has maintained her links with both academia and industry, and is looking to broaden her portfolio of clients, professional services, and affiliations over the coming months.
Kerys Mullen Quality and Hygiene Centre LDC Lever Brothers Ltd Port Sunlight Merseyside CH62 42D U.K. (Disinfectants and Public Health Biocides)
Kerys Mullen is European Hygiene Claims Advisor for Unilever Home and Personal Care. She joined Lever Brothers of Port Sunlight in 1990 and obtained an honours degree in Biochemistry through sponsorship. Initially she was responsible for developing rapid methods for hygiene control in the factory. She also developed and implemented hygiene standards as a European Hygiene Systems Auditor and spent some time responsible for product preservation. In 1998, she became the European Hygiene Claims Advisor principally responsible for developing claims and defining laboratory methods. She is a representative on UK and international bodies, including BACS Microbiological Committee and Work Group 3 for Comite´ Europe´en de Normalisation (CEN TC 216-Antiseptics and Disinfectants), which has been established to produce harmonized European test methods for antiseptics and disinfectants in the fields of food and institutional hygiene. She is also an expert advisor to the British Standards Panel TCI/80/-/5 Testing Of Anti-Microbial Treated Textiles.
Editors and Authors Dr. Roland Solecki BgVVBerlin Bundesinstitut f. gesundheitlichen Verbraucherschutz Und Veterina¨rmedizin Thielallee 88–92 D-14195 Berlin Germany (Human Health, Safety and Risk Assessment)
Roland Solecki was born in 1954 and was educated (1973 to 1978) at the University of Leipzig in animal physiology and neuro-endocrinology. From 1978 to 1991, he worked in the Institute for Plant Protection Research in Kleinmachnow as toxicopathologist in experimental toxicology studies of pesticides on rats, mini-pigs, and Japanese quails. After his doctorate, he worked for a year at the Pathological Institute of the Charite´ in Berlin. Then he undertook postdoctoral study at the „Academy for physicians further education“ from 1983 to 1986, and finished as toxicologist. Since 1991, he has worked in the Pesticides and Biocides Division of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) in Berlin. As branch head, he is responsible for coordination and management of health evaluations of pesticides and biocides. As a toxicologist, he is engaged in the human health risk assessment of active substances for the evaluation of pesticides at national and European level. As a temporary adviser, he is participating in several toxicological expert groups for pesticides and biocides of the European Union, OECD, and WHO. His experimental work in the last 10 years has concentrated on the investigation of reproductive effects of biocides and pesticides in birds.
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The Political, Social, and Economic Framework Aynsley Kellow
1.1
Introduction
Biocides are chemical agents which have come under increasing regulatory scrutiny. Yet, as Guy Eisenberg (Product Integrity Director at producer Rohm and Haas) put it, “Most people don’t even know what a biocide is” [1]. The term “biocides”, following the OECD approach, is taken here to refer to nonagricultural pesticides. There are seven broad groups of biocides: disinfectants/sanitizers; preservatives/microbiocides; antifouling products; wood preservatives and structural treatments; microbiocides for waste disposal and strip mine sites; products used in aquatic nonfood sites (molluscicides, lampricides, algicides, disinfectants); products used for vertebrate and invertebrate pest control [2]. Mention the word pesticides and most people probably think of agricultural pesticides, yet nonagricultural uses of biocidal agents are everywhere. Biocides are used in hospitals and medical establishments, in eating establishments, mortuaries, laundries, bathrooms, kitchens, air-conditioning ducts and cooling towers, on boats and marine structures, to preserve wood, in swimming pools, in oils and cutting fluids, and to kill or repel pests such as rodents and insects. They are also used to control microbes in strip mine acid, and in sewage disposal, and paper and textile mills. They have widespread uses in households or industry. As one would expect, the use of products which possess economic value courtesy of their toxic effects on living organisms also carries risks to the environment and human health, and such risks have to be managed so as to minimize the possibility of unintended biological damage. To manage such risks, most countries have adopted various regulatory regimes. These tend to reflect different histories, uses, and cultures, and this gives rise to a number of issues at the international level. Different regulatory regimes in different countries can result in barriers to trade and increase the costs of product registration. But such regimes (like any regulatory sysThe Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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tem) can also provide advantages for some economic actors, and in an age of increasing trade liberalization, regulation can be a way of re-erecting national borders. On the other hand, attempts to harmonize regulations across jurisdictions provide opportunities for some actors to seek to impose regimes which advantage them. For example, if domestic regulatory measures have favored particular chemicals and producers, the export of regulations exports advantage for domestic producers and exports disadvantage for those who have not been required to meet the standards in question. In addition to the political, economic, and social factors which influence the making of domestic risk-management policy, the relationship between domestic and international politics and policy is thus significant for the regulation of biocides. One central problem relates to the very definitional ambiguity which arises with deciding what is a biocide and what is not. Definition of the object of regulatory activity is a necessary part of any regulatory regime, because what cannot be defined cannot be regulated. How definitional terms are applied can also mean that the subjects of regulation are allocated to different agencies, each of which can have different cultures and approaches to risk. Biocides are sometimes defined and regulated as pesticides, sometimes as drugs, and sometimes as industrial chemicals. One consequence of this is that it will often be necessary here to discuss regulation of chemical products more generally, but it is an issue which also impacts upon regulation per se. The problem of definition is important because there is no single regulatory approach among OECD members, with disinfectants and sanitizers (for example) regulated as pesticides in some jurisdictions, as medicines or drugs in others, and as industrial chemicals in others. Antifouling products are regulated as pesticides in some jurisdictions and as industrial chemicals in others. As a result, the regulatory pattern is complex, with many countries having split responsibilities between different ministries and different agencies within ministries for both different biocide product types and even for the same product type. While there are few national authorities involved, there is often considerable complexity at lower administrative levels. Active ingredients have to be approved first in some jurisdictions, such as under the European Union Biocidal Products Directive, where they are placed on a “positive list” before they can be used in all products. In most countries, however, data on the active ingredients and formulated end-use product are considered together as an integrated package, but approval is only given to the end-use product (approval is then given for between four and ten years, and is often subject to conditions relating to use). Regulation of biocides is mostly aimed at ensuring safety. There is some, though little, regulation of biocides for efficacy, both in terms of initial effectiveness and the development of any resistance by target organisms. Most jurisdictions require labeling, which is taken to include hazard warnings, uses, target species, warnings or restrictions based on risk, and directions or instructions. Approval can be denied on the basis of lack of efficacy, or on the grounds that the product presents an unacceptable
1.2 Historical, Cultural, and Economic Influences
risk to humans or the environment. Human exposure assessments take into account user characteristics and formulation types and application methods. Data is usually required to be kept on usage so that monitoring can occur, so that risk assessment can incorporate “field experience”. Most countries require the storage of data on: chemical identity, physical/chemical properties, function, mode of action and handling, analytical methods, and toxicology. These different regulatory approaches reflect the differing histories and cultures of countries using chemicals. They are differences which can give rise to wishes to harmonize regulatory approaches in order to prevent the use of regulatory differences as disguised barriers to trade. These social, economic, and political factors influence the regulation of biocides and other chemicals at both the domestic and international levels, and add complexity to the risk-management process. Especially at the international level, focusing on science might be thought to be helpful in developing shared appreciations of risk, but this is inherently problematic. To understand why science does not yield identical perceptions of risk and risk-management decisions, we must understand the way in which social, economic, and political factors affect the question of risk. That is the purpose of the present chapter.
1.2
Historical, Cultural, and Economic Influences
The modern chemical manufacturing industry developed out of the munitions and dyestuffs industries [3 – 7]. Because of links between the chemical and pharmaceutical industries much of the chemical industry had had experience with regulation through pharmaceutical registration [8], when attention turned to pesticides in the 1970s. Many of the early pesticidal agents were metal salts – such as copper sulfate, calcium arsenate, lime sulfur, and lead arsenate. DDT, the first synthetic pesticide, was not developed commercially (by Geigy) until 1939. Many of the synthetic pesticides were seen as providing considerable advantages over the metal salts, many of which were known to pose acute toxicity risks to humans. Concern over synthetic chemical products developed after the publication of Silent Spring in 1962 [9], and by the 1980s the industry faced an increasingly hostile public, despite the fact that most of the serious instances of chemical hazard were acute catastrophic emergencies (at Seveso, Flixborough, and Bhopal) rather than chronic poisoning of humans or the environment through the use of synthetic chemicals [10]. The most notable cases of chronic chemical toxicity involved heavy metals (methyl mercury with Minimata disease and cadmium with itai itai). Most of the dangerous metal salts were replaced by synthetic pesticides, and initial domestic regulation focused on the safety of new products.
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Worldwide usage of pesticides doubled every decade after 1945 until the mid-1980s, when a slowdown occurred as a result of both changes in applications and environmental concerns, which effectively stabilized usage in volume terms [11]. Economies became substantially less chemical-intensive, with pesticide use in kilograms per dollar of GDP declining by half over the two decades from 1980. The costs of developing and marketing new chemical products have encouraged substantial concentration of ownership. By the mid-1990s, the top nine producers accounted for half of the world production. These were Ciba-Geigy, Zeneca, Monsanto, Bayer, DuPont, Dow Elanco, Rhone-Poulenc, BASF, and American Cyanamid. AgrEvo, a joint venture of Hoechst and Schering was the tenth largest, followed by “second-tier” companies such as Sumitomo, Sandoz, FMC, and Rohm and Haas, with sales below $ 1 billion [11]. The growing importance of biotechnology to the chemical industry has also resulted in considerable reorganization. For example, Clariant was the former specialty chemicals division of Sandoz, which later merged with the specialty chemicals division of Hoechst. Creanova Inc., formerly Huls America Inc., includes the worldwide colorants and biocides business of the North American operation of the specialty chemical business of Creanova Spezialchemie GmbH. Rhone-Poulenc has formed Merial, a joint venture with Merck in animal health, while forming a specialty chemicals subsidiary called Rhodia. Solutia is the former chemicals unit of Monsanto, while its biotechnology interests have been moved into Pharmacia (for further details of industry structure, see Chapter 2). Critical mass in the chemical industry is thought to be reached at a level of annual sales of $ 1 – 1.5 billion, which is thought to be necessary to be able to afford higher R&D costs and regulatory burdens. Producers endeavor to develop product portfolios, ideally with a flagship product, such as Monsanto’s Roundup, with estimated sales of $ 1 billion per annum. However, typically only two flagship products are likely to appear in a decade and they dominate for a while, and then when patent protection lapses, a replacement is developed. Niche products, which solve specific problems, are more common, with ten to twenty developed per decade. Substitute pesticides, marketed as supplements or alternatives, are introduced at the rate of about five to ten every decade. The chemical industry is technology driven. When patent protection expires, generic competition arises, but large firms can counter this by quickly introducing new products. Lax enforcement of patent rights is one factor which has limited investment in developing nations, such as India. As a result, production is concentrated in Canada, the US, Western Europe, and Japan. The biocides business differs from that of the large agricultural pesticides sector. In the biocides sector, smaller players have been more numerous than with agricultural chemicals, with many smaller chemical specialties companies in existence, often trading at substantially less than global scale. The biocides business is much smaller than other businesses in the chemical industry, perhaps only a tenth of the size of the plant
1.2 Historical, Cultural, and Economic Influences
protection market [12]. The sector is diverse with many small to medium companies, with some operating only on a national or regional basis. This reflects in part the small tonnages involved with specialty chemicals, but it also reflects the lower levels of regulatory scrutiny for biocides compared with agricultural chemicals, because the costs of chemical registration favor larger, global players, which can afford to meet registration costs and which can pursue international harmonization. Harmonization of registration means that the costs of registration can be spread over a larger market. The growth of biocides regulation (as we shall see below) has added to the pressures for concentration of ownership. The pattern of ownership and distribution of manufacturing capacity has meant that the chemical industry overall is dominated by transnational corporations, and this is a feature which has been important in the politics of regulation. The existence of transnational corporations larger than many small states gives rise to concerns about their power and accountability. They are feared, disliked, and mistrusted on these grounds alone, and the risks associated with their products and their manufacture provide a useful point of attack for their critics. Thus, in addition to any concerns over risks for human health or the environment, campaigns which draw attention to risks and call for their regulation become a means of weakening disliked organizations. This concern has been marked where operations have involved Developing Countries, and it has helped bring about change both as a result of regulation and from within. Ironically, the regulation of chemical risk has been driven by politics involving attacks on excessive concentration of capital, and yet this has served to produce further concentration. The disaster at Bhopal, India, where an explosion in a pesticide factory owned by Union Carbide released substantial amounts of the toxic intermediate product methyl isocyanate into a heavily populated district helped create internationally a new level of concern with toxic chemicals, and prompted the industry to develop its “Responsible Care” program to raise standards for behavior. There were complex causes in the Bhopal disaster, including the insistence of the Indian government that local staff be employed, and the intrusion of residential development into the buffer zone around the factory [13, 14]. But the Bhopal tragedy was widely interpreted as the fault of the company, and focused transnationals on the issues of liability which existed even despite the absence of effective regulation in the host country. Most resolved to demand fuller control over the staffing, design, and equipment of their foreign plants, since they would be exposed to liability in the US courts [14]. Whether or not they had previously sought to locate factories where environmental standards were lax, chemical companies were reluctant to do so after Bhopal. A UN study by the Center on Transnational Corporations shortly after found that multinational investment in hazardous industries had gravitated chiefly toward countries with advanced industrial economies and firm pollution controls [14]. Despite this, there has
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been much talk of “toxic colonialism” since Bhopal, aided by concerns over the export to Developing Countries of some chemical products no longer licensed in “Northern” nations. This is a highly complex area. During the negotiation of the Rotterdam Treaty (on prior informed consent for trade in chemicals), Developing Countries such as Malaysia floated the idea of restrictions on exports of chemicals from OECD countries into Developing Countries, relying upon the “toxic colonialism” rhetoric, but clearly with the aim of providing mechanisms which might encourage investment in such countries to circumvent the trade barrier thus created. Even the issue of the export of “obsolete” chemicals to the developing world is not a simple one. The negotiation of a treaty on persistent organic pollutants (POPs, concluded in Johannesburg in December 2000) ultimately permitted the continued use of DDT in Developing Countries, acknowledging that it was cheap and effective in combating malaria, although it had passed out of patent and was able to be made cheaply by generic chemical manufacturers in Developing Countries. The elimination of malaria in Europe and North America came as the result of various social and economic changes, but most significantly only after the development of DDT [15]. Only in the 1970s was Europe considered malaria free, and even the World Wide Fund for Nature acknowledged the strength of the claim for exemptions from Developing Countries from proposals to phase out DDT. The risk-benefit calculus of DDT is different for poor tropical countries, which are less concerned over effects on wildlife than are affluent countries. These characteristics of the chemical industry, especially the prominence of transnational corporations and issues involving the Third World, such as differing perceptions of environmental risk resulting from different stages of development and questions of the export of chemicals which might still be accepted for use in some countries, affect the way in which risks of chemicals are perceived (in ways we shall examine below). There are many complex issues here, including matters relating to patents, since many “obsolete” chemicals can be made cheaply as generics, and calls to restrict exports serve to provide market protection for new, patented chemicals, to the advantage of the transnationals.
1.3
National and International Regulation
Environmental regulation of toxic chemicals began at the domestic level and focused initially on pesticides. The US Environmental Protection Agency (EPA) was given authority to register pesticides in 1972, and these powers were soon mirrored in other industrial countries, particularly Japan, and the European Community (now European Union), and Nordic countries [16, 17]. Industry feared that it would suffer the costs of
1.3 National and International Regulation
having to register its products separately in each jurisdiction, and pushed for international harmonization. It was supported in this by the US food industry and agricultural exporters such as Australia and Canada, which feared that the European Union would use internal pesticide regulations as nontariff barriers to trade [18]. The Codex Alimentarius Commission in The Hague, a joint Food and Agriculture/World Health Organization (FAO/WHO) body, was established to address this issue, and established a system designed to harmonize the basis for national regulation of food (see below). There have been three waves of concern which have driven the regulation of biocides and other chemicals. The first was the set of issues highlighted by Rachel Carson. Prior to Silent Spring, modern chemical agents were considered relatively safe. They lacked the acute toxicity of the metal salts and other agents they replaced. As a result, they were used with little care and in copious quantities. DDT, for example, was widely employed to attack mosquitoes in much of Europe and the United States, where malaria was endemic until the latter half of the Twentieth Century [15, 19]. Things which are perceived to constitute small hazards often become large risks because our risk perceptions cause us to behave in ways which increase the probability of harm, and this was the case with DDT. Silent Spring fostered concern which eventually drove regulation, the development of nonpersistent chemicals, and the development of integrated pest management, but its most immediate result was that it encouraged greater caution in the application of chemicals. The second wave of concern was the “War on Cancer” declared by President Nixon in the US. It is important to note, however, that cancer concerns and regulation had been around for a decade previously. The 1958 Delaney Amendment to the Food, Drug, and Cosmetics Act required that processed foods must not contain residues of any pesticides which induce cancer in laboratory animals. This included 36 pesticides including: mancozeb, a fungicide used on cereals and grapes; dicofol, an insecticide used on fruits; and captan, a fungicide used on plums, grapes, and tomatoes. The modern concern over cancer stemmed from a conclusion at a 1968 conference that as many as 80 percent of malignant cancers might be attributable to “environmental” causes. There followed a popular misinterpretation of what the term “environmental” means. In medical and scientific idiom, “environmental” means anything not genetic – stress, diet, and so on. In fact, the research upon which the conference statement was based specifically included dietary differences as variables, and therefore included all the natural dietary carcinogens discussed by Bruce Ames et al. [20], who have pointed out just how elusive a quest for a world free from chemical risk is likely to be if we were to eschew the use of chemicals known to cause cancer in laboratory rats. As they demonstrate, the greatest human exposure to pesticides comes not through exposure to anthropogenic pesticide residues, but from the ingestion of naturally occurring pesticides present in the food we eat.
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This 1968 attribution of cancer to “environmental causes” suggested cancer was avoidable, if only environmental exposures could be identified and managed. It coincided with the rise of environmental politics, and “environmental” was widely interpreted in a different sense than its technical application in epidemiology. The result was Nixon’s declaration of war on cancer in which the imperative was to identify which carcinogens to avoid. In 1967, there were about 500 animal carcinogens, but this had grown by 1976 to 2400 after a great deal of expensive testing. Then, Epstein’s The Politics of Cancer [21] was published and became a best seller, fuelling popular concern over chemical carcinogens. Scientific advances since then have made the task of chemical regulation more, rather than less, difficult. For example, the US Food Quality Protection Act of 1996 attempted to deal with inconsistencies arising from the fact that the Delaney Clause applied to processed foods but not raw commodities, together with the fact that testing had indicated that many chemicals could breach Delaney if found in trace amounts [22]. Its impact provides some insight into chemical regulation. A National Academy of Sciences Report [23] estimated that 60 percent of the herbicide, 90 percent of fungicide, and 30 percent of insecticide use by weight consisted of materials classified by the EPA as carcinogenic to laboratory animals or potentially so to humans. FQPA reflected the impossibility of applying Delaney in practical terms when test protocols turned up numerous rodent carcinogens among existing products, and it had become possible to detect residues at levels of one part per quadrillion. There are problems in relying on the use of results tests involving massive doses of chemicals on laboratory species as a proxy for carcinogenicity in humans. Not only does the sensitivity of species vary markedly – even between rats and guinea pigs, let alone between those species and humans – but such tests typically involve the administration of massive doses administered in ways which often do not reflect probable exposure paths. Test protocols for examining the effects of chemicals on animals were developed as a means of screening new chemicals, and doses given to laboratory animals can be as much as 35 000 times those likely to be found in typical human exposures and are often introduced directly into tissues. If a new synthetic chemical is found to be carcinogenic or teratogenic in laboratory test species, that is a very good reason for restricting its use, subject to further testing, but many things proved to be carcinogenic in massive doses, and there is little point in banning substances long in use solely on the basis of a screening test. Nor does this approach guarantee protection, for chemicals might be human carcinogens even though they have no effect on laboratory species (as is the case with a species of arsenic). The difficulties of chemical testing have been exacerbated by ethical considerations, with animal rights concerns creating pressures for less reliance on animal testing. Animal rights campaigners in the United Kingdom have targeted the testing company Huntingdon Life Sciences with a number of violent actions, and thus created political
1.3 National and International Regulation
pressures which might result in greater reliance having to be placed in future on in vitro techniques which are even more unrealistic as means of assessing hazards. The third wave of concern has centered on the possible endocrine-disrupting effects of very small amounts of some chemicals, either alone or synergistically with other chemicals [24]. These claims are controversial, with sceptical scientists quick to point out that there are many naturally occurring chemicals which mimic endocrines, including phytoestrogens in many foods, such as coffee and soy products. The process of evaluating chemical risks is difficult and expensive. In the US, a typical pesticide is put through more than 100 tests, and approval can take more than three years [11].Brian Wynne once noted that there were (then) approximately 7 000 000 known chemicals, 80 000 of which were in commercial circulation. Approximately 1000 new chemicals entered commercial use each year. Using total world laboratory resources, about 500 chemicals could be tested each year. One test for carcinogenicity can involve 800 test animals, 40 different tissue specimens per animal, and a cost of $ 500 000 over three and a half years [25, pp.48 – 49] (the costs have inevitably risen). What gets chosen for toxicity testing, by whom, and by what methods are crucial political questions. Only about 7000 chemicals had been tested for carcinogenicity, and only about 30 had been demonstrated to reasonable standards of proof to cause cancer in human populations. Much of our work in managing chemical risk thus takes place in at least partial ignorance. More recently, the focus has shifted from new to existing chemicals, often with some attempt to more complete assessments of risks, not just to human health, but to the natural environment. The costs of moving from toxicity testing to a full-blown risk assessment, which considers actual exposures and pathways, are even greater than those for toxicity testing. The growing importance of environmental risk has thus added to the task of evaluating chemicals, because complex ecological factors cannot be satisfactorily explored by following laboratory testing, be it in vitro or in vivo. But detailed environmental risk analysis is very costly, and these costs are having an impact on the nature of the market in both agricultural pesticides, where product runs are large, and (especially) biocides, where markets are often too small to justify the expense of re-registering many existing chemicals. With the addition of ecological complexities, there is an inevitable temptation to either “let the toxicity do the talking” or to engage in some “quick and dirty” risk analysis via some formula, which will approximate a risk analysis. Both these alternatives result in the reduction of chemical risk policy to a technical level which is likely to privilege technical specialists since they remove the evaluative and economic dimensions from the risk-management process and leave the toxicity specialists firmly in control. Such specialists are more likely to operate on a technical rather than cultural theory of risk, and are likely to be somewhat myopic towards the social, economic, and political dimensions, which are the realm of the subjective risk professionals, but the
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result – especially when combined with the moralistic and highly charged politics generated by the environmental movement – is potentially a contamination of the “science” of toxicity and ecotoxicity by evaluative processes which are implicit rather than explicit [26]. Chemical risk management can never be undertaken solely on the basis of scientific knowledge of toxicity. In theory, all chemicals are toxic. In practice, risk management must consider the ways in which people or other living things can be exposed to such toxic substances in amounts that can cause harm, the probability of such exposure occurring, and the hazards they pose. To manage or reduce the risks associated with hazardous chemicals requires consideration of the costs as well as the benefits of such an action, where costs include opportunity costs as well as any risks associated with the use of any substitute or pursuit of any alternative practice. This requires an understanding of hazard identification, risk estimation, risk evaluation, and risk management. Most models for risk assessment and risk management commence with some form of hazard identification, using scientific research to establish the nature of some adverse effect [27]. The notion of risk involves both the hazard and the probability of its occurrence, and risk estimation thus involves probabilities. Hazard identification and risk estimation involve primarily the use of toxicological and epidemiological data as their primary sources of knowledge, although structure/activity analysis may also be used in the case of chemical hazards. Risk estimation must also involve some consideration of human activities, the uses to which chemicals are put, the form in which they are used, and so on. Risk evaluation inevitably involves the social science disciplines, with public policy considerations becoming paramount in the evaluation of advisory, economic, or regulatory options using the formal tools of program evaluation, “tempered by the public’s perception of the risk involved as well as prevailing socio-political factors” [27, p.404]. Finally, risk management involves the implementation of the control strategy selected – again, a process which has more to do with the social sciences than the natural sciences. As Krewski and Birkwood [27, p.405] note, “Hazard identification and risk estimation are clearly in the scientific realm, whereas risk evaluation and risk management fall within the domain of social decision-making”. Risk evaluation inevitably involves both the notion of risk as a social construct and the consideration of economics. Importantly, trade-offs must be considered. We cannot live in a risk-free world, and any alternatives we might consider also carry risks. Economics addresses this point neatly with its notion of opportunity cost – what we have to give up in order to choose a particular course of action – although economics itself cannot provide an objective science of risk management. A risk-management approach calls for the following steps to be taken:
1.3 National and International Regulation
1. Before taking action to regulate an environmental problem, an objective assessment of scientific knowledge must indicate that exposure to the pollutants of concern may represent a significant danger to human health or the environment. 2. To make efficient use of resources, environmental problems should be ranked in order of priority by some formal or informal “comparative risk” process. 3. The proposed actions should reduce the risks of targeted pollutants by a greater degree than they increase other risks to public health and the environment. 4. The economic costs of the action must be balanced against the expected benefits of risk reduction. Such balancing might be quantitative or monetary (where possible) but might be in many cases more qualitative and judgmental [28, pp.1 – 2]. Politics often drives risk regulation, so that these principles are not followed, at considerable cost. For example, Tengs et al [29] examined the cost effectiveness of 587 lifesaving interventions, including conventional medical intervention, injury reduction measures, and toxic chemical regulations. While it ignored any environmental benefits of chemical regulation, this analysis revealed just how powerful the political pressures for chemical regulation were, and how great the costs were of regulating so rigorously. Overall, the median intervention cost $ 42 000 per life year saved. The median medical intervention cost $ 19 000/life year; injury reduction $ 48 000/life year; and toxic chemical regulation $ 2 800 000/life year. Put another way, studies of the relationship between societal income and mortality in the US indicate that a reduction of income of about $ 12 million may cost one statistical life. Since many regulations cost more than this per life saved, they literally cost more lives than they save [30]. Despite the fact that the Reagan administration in the US imposed a benefit-cost test requirement on regulations, the US Office of Management and Budget (which oversees risk-regulation agencies) has never rejected a regulation with a cost under $ 100 million per life saved. This fact reflects the subjective elements in risk management. To a very large extent, risk-management approaches reflect the methodologies employed to estimate risks and evaluate them, as well as various institutional and social factors. One of the more farcical examples of the result of different institutional factors embodying differing risk-management approaches concerned the US Department of Agriculture and the US EPA. The USDA had responsibility for regulating permissible levels of pesticide residues on agricultural produce, and its standards were understandably more sympathetic to its agricultural clients than were those of the EPA, which had responsibility for setting limits for chemicals disposed in solid waste dumps. The result was that at one time a sprayed apple which could be sold for human consumption under USDA regulations could not be disposed of in a landfill under US EPA regulations [25, p.49]. Another example can be used to show how different methodological approaches followed by different agencies produced substantially different assessments of
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what level of risk was socially acceptable. Radiation hazards frequently arouse considerable anxiety on the part of the public, yet risk-management processes followed in the United States produced regulatory outcomes markedly different for radiation hazards and chemical hazards, and this difference was an artefact of the methodologies employed. Permissible occupational exposure to radiation in the United States would lead to an additional lifetime probability of death of well in excess of one in 100; typical limitations on exposure to chemical carcinogens corresponded to an increased probability of about one in 1000. This order of magnitude difference reflected the histories of the two regulatory approaches. Radiation risk management evolved under the assumption that risks should be balanced against the benefits of radiation and radiation-producing technologies and “taking into account the unavoidable natural sources of background radiation” [31, p.2336]. Chemical risk management developed from a different background and embodied different assumptions. It was assumed that public health could be completely protected, and assumed (because the program was dealing primarily with screening new chemicals for registration) there were no significant natural sources of the chemicals – an assumption which Ames et al have shown cannot be safely made. Moreover, rather than dealing with epidemiological observations in humans, chemical risk management was based upon projections from experiments performed on laboratory animals. The differences between the two approaches went largely unnoticed until the US EPA began treating radiation risks in the same context as chemical risks, and found that applying standard chemical risk-management criteria to radionuclides produced limitations on excess radiation doses that were unworkably small in comparison to natural background radiation. Chemical risk assessments were likely to produce overestimates of human risk thanks to two factors. First, because of the uncertainty in predicting risks at low doses based on risks observed at high doses, most regulatory agencies used the upper confidence limit of risk measures, feeling that they are erring on the side of caution. Second, some agencies (including the EPA) further used a conservative “surface area scaling rule” to predict human responses from animal bioassays. Moreover, as the first chemical risk assessments were conducted for synthetic carcinogens, there was assumed to be no naturally occurring background level to be subtracted from additional exposures in risk assessments, so background risks came to be seen as irrelevant. This has consequences for the application to existing chemicals (including naturally occurring chemicals) of techniques developed to detect any carcinogenic potential associated with new substances. This outcome was facilitated by political factors and legal judgments, which underscores the point that risk assessment is a highly political process. Political institutions, political culture, power, and interests all affect the development and implementation of risk-management processes [32 – 34].
1.3 National and International Regulation Table 1.1.
Activities increasing probability of death by one chance in a million (Source: [35, p.219])
Smoking 1.4 cigarettes Spending one hour in a coal mine Living two days in New York or Boston (air pollution) Travelling 300 miles by car Travelling 10 miles by bicycle Flying 1000 miles by jet Living two months with a cigarette smoker One chest X-ray in a good hospital Eating 40 tablespoons of peanut butter (aflatoxin) Drinking 30 cans of diet soda (saccharin) Living 150 years within 20 miles of a nuclear power plant (low-level radiation) Living within five miles of a nuclear reactor for 50 years (accidental release of radiation).
Risk perception is influenced by all manner of influences. The way in which evaluations of risk affect our perceptions can be illustrated by reference to various kinds of risks to which we are commonly exposed. The activities set out in Table 1.1 have the same probability of causing death. This list shows how our perceptions of risk vary. Few people would think twice about driving 300 miles in a car, yet some of these refuse to fly. Most environmentalists would happily ride ten miles to work on a bicycle, but would refuse steadfastly to live near a nuclear reactor. Probability theory cannot explain this. People engage in risky activities all the time, but our perception of those risks, and our willingness to accept them, varies greatly. The distribution of risks is also important: car deaths occur disproportionately with young males, so a fear of flying among females and the middle aged is not as irrational as it might seem. Chemicals pose hazards which have been estimated epidemiologically, but such an estimate depends upon many social factors which might affect exposure and probabilities, so it cannot be taken as a substitute for a risk assessment – at least not without some risks. Drinking water chlorinated to the maximum level permitted by the US EPA carries an annual probability of death of 0.8 per 100 000, largely from bladder cancer. But the risks of unchlorinated water are usually considered higher, and (to put the risk in perspective) the annual rate of death from all causes is 1000 per 100 000 [35, p.218]. There are serious dangers in trying to reduce risk assessment of chemicals to toxicological science and ignoring the social and economic context. One example of this comes from the use of a US EPA risk assessment for chlorinated water in Peru. Peruvian officials decided to follow the lead of the US EPA and not chlorinate the water from many wells. In the ensuing cholera epidemic, more than 3500 people were saved from bladder cancer by an early death [36]. General public
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health conditions in the United States make the probability of cholera remote, and cancer is likely to loom larger in a risk assessment of chlorinated water there than in Peru. The figures in Table 1.1 do not tell us why some risks are accepted, while others with a lower probability of occurrence are deemed unacceptable. To put it simply, it matters how we die, not just whether and when. We know some of the factors which affect the assessment of various kinds of risks by individuals, and these are shown in Table 1.2, which indicates factors found to result in risk perceptions being amplified or reduced. These assessments reflect broader cultural and political forces which are driving the politics of risk. Anthropologist Mary Douglas [26, p.15] sees the environmentally based preoccupation with risk as having to do with blame, and as, at least partly, a public backlash against the large corporations. According to this view, the almost obsessive preoccupation with avoiding dangers, which are (objectively) much more remote than those we are exposed to every day, is a reaction to the vulnerability and loss of control we feel in an era of globalization, especially with chemicals which are made by the transnational corporations that engender many of these fears. The last pair of factors in Table 1.2 points to a vexed problem with chemical safety and thus to chemical and drug registration (and, more recently, with the products of genetic engineering). Most of the research is conducted by the scientists of the appliTable 1.2.
Factors in risk assessment (Source: Adapted from [37, p.18]).
Risk considered greater
Risk considered less
Man-made risks
natural risks
High loss of life accidents
low fatality accidents
Immediate effects
delayed effects
Risks to nonbeneficiaries (residents near industry)
risks to beneficiaries (workers in industry)
Involuntary risks (contaminated food)
voluntary risks (smoking)
Uncontrollable risks
controllable risks
Unfamiliar risks
familiar risks
Imposed risk (budget cuts lowering safety)
self-chosen risk (using a vaccine)
Risk from secret activities (waste from a secret lab)
risk from open activities (waste from a mine)
Risks to children
risks to adults
Known victims
“faceless” victims
Irreversible effects
reversible effects
Scientific uncertainty
scientific certainty
Untrusted institution
trusted institution
Risks evaluated by industry
risk evaluated by unbiased groups
1.3 National and International Regulation
cant company, or under research contracts let by the applicant. Some details, often including the formula of the substance, are kept confidential in order to protect intellectual property rights. Regulatory authorities have reached accommodations with industry, and regulatory systems including audit processes are in place, but the tensions between open science and confidentiality facilitate claims that regulators and contract researchers – if not the whole scientific process – have been corrupted by the economic power of industry [38]. Dismissing scientific findings because they were produced by a scientist who has at some stage “worked for industry” is thus a powerful weapon for amplifying risk perceptions, even though it commits the genetic fallacy (the validity of science is not determined by its origins), and is somewhat meaningless, since most scientists will be “guilty” by some tenuous association. But, at a time when government scientific regulatory institutions are falling into distrust, this can be damaging. Levels of trust are one of many things which are likely to vary across nations. and are possible sources of variation in risk assessments and thus management policies. Given the inevitable variation among risk assessments performed at the national level, how do we secure international agreement for action or inaction at that level? How can we gain the advantages harmonized approaches can bring, while allowing inevitable (and sometimes desirable) national variations in approach, and at the same time preventing national standards from being used as disguised barriers to trade? One temptation is to resort to scientific reductionism, to regulate on the basis of toxicity testing alone, but this will ignore questions of bioavailability as well as differing national uses, exposures, and values. The recent prominence given to the precautionary principle is an example of this phenomenon. While the precautionary principle properly interpreted is a reasonable injunction not to allow residual scientific uncertainty to serve as a reason for delaying preventative action (though it does not and cannot tell us how much precaution is prudent), it is often misinterpreted as meaning that a single piece of scientific evidence is sufficient to then place the burden of proof on a chemical producer to show that a chemical is safe. There are differences between the US and the EU over how the precautionary principle is interpreted, but even within the US there are legislative enactments which differ in the way in which they impose the burden of proof. For example, the burden of proof lies with the Food and Drug Administration over food ingredients, but the producer bears the burden of proof with the licensing of new pharmaceuticals. The proponents of the Toxic Substances Control Act initially assigned the burden of proof to producers, but as enacted, TSCA placed the burden of proof on the EPA [39, p.171]. These factors have given rise to various regulatory approaches in different countries, but trade matters have also affected the response. The US saw the international focus on the registration of new chemicals as uneven in its impact, since this was an area
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where its chemical industry enjoyed advantage. It therefore pushed for international regulation to be extended to existing chemicals, an area where the chemical industry in the European Union was seen as having advantage [40]. It worked for regulation to be extended to existing chemicals in international arenas such as the OECD Chemicals Program (see below), but it also undertook a process of re-registration of existing chemicals at the domestic level, including biocides, which had the effect of disadvantaging imported biocides. There are numerous intergovernmental organizations which deal with international matters related to the regulation of chemicals, and we shall now examine these briefly before looking at the different trajectories followed by biocides regulation in the US and the EU.
1.4
International Organizations and Chemicals
The Codex Alimentarius Commission (mentioned above) was established in 1962 jointly by the UN World Health Organization and the UN Food and Agricultural Organization. Its current membership is over 160 countries, and its official mandate is to implement the Joint FAO/WHO Food Standards Program, among the aims of which are to protect the health of consumers and to ensure fair practices in the food trade. Members adhere to the Codex voluntarily. The Codex volumes cover specific food areas, or methods of analysis and sampling, and may also contain general principles, definitions, codes, methods, and recommendations. The Codex contains food standards for commodities, pesticide residue limits, codes of hygienic or technological practice, guidelines for contaminants and evaluations of pesticides, food additives, and veterinary drugs. While Codex has more relevance for agricultural pesticides, it thus has the potential to affect biocides which might be present as contaminants in foods. In many ways Codex is a model for the integration of risk management in other areas into international agreements, including the WTO agreements because it is science-based and sets out agreed hazard information, while leaving risk management to national authorities. This is an approach which is finding favor in the evolving trade regime – for example, the Sanitary and Phytosanitary (SPS) Agreement governing quarantine matters [41]. Such approaches limit arbitrary decision-making to use risk-management decisions as disguised barriers to trade while preserving the sovereign capacity of governments to exercise discretion within prescribed rules. The OECD, as we shall see, has played an important role in harmonizing chemical risk management, but there are, however, developments within the UN system which both limit sovereignty and allow scope for trade-restrictive action.
1.4 International Organizations and Chemicals
The Organization for Economic Cooperation and Development (OECD) is an intergovernmental organization established in 1960 with democracies with advanced market economies as its members [42]. Its aims and responsibilities are to promote sustainable economic growth and employment, to promote economic and social welfare, and to stimulate and harmonize the efforts of its members in assisting developing countries. Much of its work is aimed at achieving harmonized policy approaches between member states, and its standards have assisted the development of internationally accepted test protocols and laboratory practices, allowing both reduced costs through mutual recognition approaches and transparency of national risk-management decisions which might serve as trade barriers. The OECD has numerous specialist committees and subsidiary groups in which representatives of member governments participate. In 1970 the OECD established an Environment Policy Committee (EPOC), serviced by an Environment Directorate, to promote the integration of environmental and economic policies, reduce pollution, assess environmental performance, develop environmental protection tools, and improve international data and information on environmental issues. It has a number of activity areas in divisions, including an Environmental Health and Safety Division, within which is located the OECD Chemicals Program. The Chemicals Group was first established by the OECD in 1971, and its work was expanded in 1978 with the creation of a Special Program on the Control of Chemicals. This development of the group’s activity in the 1970s took place within the dramatic context provided by events such as the chemical works explosion at Flixborough in 1974, and that at Seveso in 1976 [43]. The Program commenced by dealing primarily with safety issues relating to specific chemicals such as PCBs, mercury, and CFCs, but it developed to take on a role in creating and harmonizing chemical testing and hazardassessment procedures. This was aimed not only at allowing risk assessments of new chemicals before they were introduced, but at ensuring some degree of standardization, to ensure that differences in national legislation did not create barriers to trade. To these ends, the Program established Test Guidelines (1981), Principles of Good Laboratory Practice (1981), Mutual Acceptance of Data generated in accordance with these practices and guidelines (1981), and a Decision on the Minimum Pre-marketing set of Data (MPD) required for the licensing of new chemicals (1982). All of this activity can be seen as ensuring that regulation of chemical products did not interfere with trade, and was able to proceed on a basis which delivered some economies through scale and avoidance of duplication. International concern then began to develop over the risks of existing chemicals, and in 1987 the OECD Council adopted a decision to strengthen and harmonize existing policies to bring about the systematic investigation of existing chemicals. As a result, the OECD commenced the cooperative investigation of high-volume chemicals (those produced at rates in excess of 10 000 tpa in one country or more than 1000 tpa by more
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than one company). The OECD developed the Screening Information Data Set (SIDS), closely resembling MPD, to share the burden of assembling the minimum data for determining whether a chemical was sufficiently hazardous to require further investigation. These data were then forwarded to various UN bodies such as the International Program on Chemical Safety (IPCS). This move to deal with existing chemicals was the result of political action by the United States, which saw itself as disadvantaged by the focus on new chemicals. As a former USEPA official has noted, during the 1970s in the OECD the US was continuously confronted by European requests for agreement on more restrictions on the development of new chemicals, an area where the US had an edge: The same countries opposed efforts to review the possible hazards associated with chemicals which were already on the market. These chemicals had found their niches in Europe, and the European governments were not eager to sacrifice them. While representatives of all countries were presumably motivated by environmental concerns, priorities were surely influenced by economic interests [44, p.239]. Industry played, and continues to play, a significant role in this process, with the Business and Industry Advisory Council, national chemical industry associations, and individual companies assisting with the promotion of data collection and ensuring the expeditious completion of testing. Again, the test results, if performed in accordance with OECD Test Guidelines and GLP, are accepted throughout the OECD. The International Program on Chemical Safety was established in the aftermath of the United Nations Conference on the Human Environment (UNCHE) in Stockholm in 1972. In 1980, the World Health Organization (WHO), International Labor Organization (ILO), and United Nations Environment Program (UNEP) agreed to cooperate in the program to coordinate work on health, labor, and environmental aspects of chemicals. IPCS has worked closely with the OECD and provides evaluated data which are intended to form a basis on which relevant national authorities can establish policy. These include Environmental Health Criteria (EHC) documents, essentially peer-reviewed statements of hazard designed to assist risk evaluation for human health and the environment at the national level. EHCs have been completed for many chemicals. IPCS Health and Safety Guides (HSGs) are short documents summarizing toxicity information in nontechnical language and providing advice on safe handling and storage, first aid, and so on. There has been long-standing cooperation between IPCS and scientific bodies such as the International Life Sciences Organization (strongly supported by the food industry), the chemical industry, professional scientific and technical societies, and workers’ federations and associations.
1.4 International Organizations and Chemicals
A call for greater activity and coordination of risk management of chemicals was made at the United Nations Conference on Environment and Development (UNCED) in Rio de Janiero in 1992, through Chapter 19 of Agenda 21. This work increasingly has moved outside the OECD to the International Program on Chemical Safety (IPCS), the Intergovernmental Forum on Chemical Safety (IFCS), and to UNEP. Chapter 19 of Agenda 21 identified six work programs: expanding and accelerating the international assessment of chemical risks; harmonization of classification and labeling of chemicals; information exchange on chemicals and chemical risks; establishment of risk-reduction programs; strengthening of national capabilities and capacities for management of chemicals; prevention of illegal international traffic in toxic and dangerous products. UNCED also decided international work on chemicals should be strengthened and better coordinated. WHO, UNEP, and the ILO were to be the focus, but the work of the OECD, FAO, and the European Community was also to be coordinated. Finally, intergovernmental mechanisms should be established where chemicals could be dealt with in an intersectoral manner. In response to this last point, an international conference was held in Stockholm at the end of April 1994, at which was established the Intergovernmental Forum on Chemical Safety. There was representation from 114 governments and over 20 NGOs. Sweden was elected president, and an intersessional group (ISG) was established with a membership of 26. This Forum was to identify priority actions in order to carry out the UNCED strategy. Specified actions were to be completed by the 1997 UN General Assembly special session to review the results of UNCED. On an interim basis, the secretariat of the IFCS was co-located with the IPCS and administered through WHO. The Commission on Sustainable Development established to oversee implementation of Agenda 21 gave the IFCS initiative strong support and called for a close association between IPCS and the Forum [45, p.23]. It was seen as very important that the work of IPCS should be the best possible science, and that only the IFCS should consider policy considerations. Every attempt was thus made to keep the technical work separate from the policy work. While there were advantages in co-locating the two secretariats, therefore, there was a case for trying to ensure that the outside world saw the IPCS as independent in its technical evaluations, removed from any commercial considerations. IPCS had had problems in the past with the United States National Institute of Occupational Health and Safety (NIOSH) because of strong lobbying by industry, and there was a perception that much of what has happened in US chemical regulation resulted from advocacy rather than consultation and consensus. IPCS had tried unsuccessfully to involve the WTO in consultations over the trade implications of its activities. The UNEP governing Council approved the commencement of negotiations to develop a convention on Prior Informed Consent for trade in toxic chemicals in May 1995. Such a convention (the Rotterdam Convention) has been concluded, as has an-
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other to phase out persistent organic pollutants (POPs). Trade restrictions under these conventions will prevail in any conflict with WTO rules (where all parties are members of both) because the subsequent agreement prevails in international law. These developments are therefore important, as are the IPCS and IFCS. Restrictions on chemical trade have already begun to appear under the Rotterdam Convention. In 2000, the European Commission approved the implementation of import restrictions on 13 hazardous chemicals under the Rotterdam Convention, requiring prior informed consent of authorities in importing countries. Five of these substances were already banned or severely restricted: binapacryl, captafol, hexachlorobenzene, and toxaphene. The eight others (lindane, 2,4,5-T, chlorobenzilate, methamidophos, methylparathion, monochrotophos, parathion, and phosphamidon) were being reviewed under EU legislation on pesticides and biocides. The European Crop Protection Association supported the restrictions because most were old and obsolete [46]. It is not just explictly chemical conventions which are important for biocides, however, as regulation can occur under other regimes. For example, the International Maritime Organization (IMO) agreed in December 1999 to ban the use of tributyl tin (TBT) biocides in antifouling paints for ships. A ban of painting ships with TBT antifouling paints was to come into effect on 1 January 2003, and a ban on the presence of TBT on ships hulls was instituted from 1 January 2008. This ban was opposed by the Organotin Environmental Program Association (ORTEPA) which represented TBT producers, including Elf Atochem and CK Witco, but benefitted those companies which had developed alternatives, such as Ciba, Rohm and Haas, Arch Chemicals, and Azko Nobel, again highlighting the way in which regulation creates winners and losers [47]. As indicated above, the US and EU have different histories of chemical regulation, with each seeking advantage through regulation. This applies both for crop protection chemicals and biocides, and the differences in approaches have impacted upon the economics and structure of both sectors of the chemical industry. As a result of the EPA call-in for data review after the US EPA first required biocide registration in 1987 and 1988 amendments to the Federal Fungicide, Insecticide, and Rodenticide Act, about 100 of the 300 active ingredients called in were removed from the market, and the number of players was reduced [48]. It was feared that the development of a new product could escalate in cost to the extent that it would be well beyond the capacity of small producers, although actual costs were only estimated to be $ 2 – 5 million, with a time of 3 – 5 years from drawing board to market. By 1994, almost half the products which had been on the market in 1987 had been withdrawn. The number of registered active ingredients in biocide applications dropped from about 1600 in 1976 to about 400 in 1993 [49]. The 1988 FIFRA amendments alone are estimated to have resulted in 232 existing chemicals being withdrawn
1.4 International Organizations and Chemicals
from the market [22]. There was a general trend away from heavy metals in biocides and towards chemistries which used less chlorine and released less formaldehyde. A similar impact flowed from the US FQPA, which dealt with cumulative risk from all currently licensed uses, meaning that if risks from current uses exceeded the overall standard, a chemical would have to be withdrawn from some uses. There were industry concerns that this would create an incentive to cancel some current uses in order to keep residue tolerances below the standard or permit new uses, and that there were thus incentives to cancel uses for small-market crops in order to minimize the impact on sales. The withdrawal of products had implications for the implementation of re-registration, because it had been intended that the process be self-financing. The review of existing pesticides in the US under the 1988 amendment to FIFRA ran into resource problems because it was to be funded by a one-off fee and annual maintenance fees on registered products. But the revenue base shrank because the regulatory effort resulted in the withdrawal of substances from the market, leaving a shortfall of $ 35 – 40 million in the funds needed to undertake the re-registration of products by the 1997 deadline [50]. This was also to mean that when the EU moved later to re-register existing pesticides and biocides, there were substances still on the European market which had been withdrawn from the US market rather than having been evaluated there. Many of these were then withdrawn in Europe rather than their producers paying the costs of registration, so the lack of international harmonization has resulted in the loss of products which might have been retained on the market had registration costs been spread over both the US and Europe. The EU Biocidal Products Directive (98/8/EC) came into force on 14 May 2000 (it was adopted on 16 February 1998, but the deadline for integrating the Directive into the national law of member countries was 14 May 2000; see Chapter 3) [51]. Existing registration procedures in Canada and the US, being harmonized through the OECD Biocides Steering Group, were ignored in formulating the BPD in the EU, which opted for its own system with higher data requirements. Industry would have welcomed a single risk-assessment procedure [1]. One estimate of the costs for additional data required for a risk assessment and therefore to support an active substance under the EU Biocidal Product Directive is $ 2.25 – 5.3 million. If 500 active substances are supported, the total cost to the sector will be $ 1162 – 2656 million. These costs will mean that small-market active substances are likely to be withdrawn from the market regardless of whether they are environmentally preferable to others simply on cost grounds. Further, the directive is likely to limit innovation as R&D budgets are diverted to regulatory purposes [12]. Many of the 1500 – 2000 biocides currently on the European market were never registered in the US, where some of the necessary data would have been gener-
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ated [1]. Among the beneficiaries of the BPD were therefore expected to be companies such as Huntingdon Life Sciences which specializes in safety, health, and environmental testing. It was expected that the costs of registering an existing biocide would cost around $ 6 million, and a new biocide around $ 9 million, a sum which would take 25 years to recover for most products. As a result of the BPD, attention was likely to turn to new formulations using existing active substances in synergistic combinations, rather than attempting to develop new active substances. Ironically, it was expected that the BPD would expand the markets for halogenated and phenolic biocides, with annual growth rates of 3.5 and 2 percent, respectively, forecast [52]. The BPD provides for a ten year transition period for registering products, but critics have argued that this is inadequate and have pointed to the experience with the Plant Protection Products Directive (91/414/EEC) implemented in 1991 with a similar implementation period for 600 pesticides. After seven years, only one product had been registered [1]. The PPPD came into force fully in July 1993, with the first stage of the PPPD process covering 90 active substances. Producers had to officially notify the European Commission of their support for a specific active substance, and then had 12 months to produce complete technical dossiers containing a series of safety studies. Of 90 active substances covered, 86 were notified. A dossier was also required on at least one PPP containing the active substance in the context of a real situation, a task which was particularly onerous and costly, with the expense running into millions of dollars. Several active substances were supported by several producers, and the intention was that they would cooperate in generating the missing studies and submit a joint dossier for the full review, but this rarely happened, and rapporteur competent authorities were required to pool separate dossiers and evaluate the complete data package produced [50]. There were also free-rider problems with the provision of data. Limited periods of data protection mean that those carrying out the work would be penalized compared those that did not produce data. It was intended to complete the PPP process by July 2003. By 2000, only two existing active substances had been fully assessed and listed in Annex I as approved substances. As a result, the Second Review Regulation for the PPP Directive abandoned separate rounds and attempted to deal with all the remaining existing active substances together [50]. The experience with the PPP does not augur well for the BPD, with indications that the timetable is unrealistic, that it will result in removal of products from the market and assist further concentration of capital in the industry, ironically, a factor which heightens risk perceptions. Further, inasmuch as it appears to be enhancing the market prospects of halogenated and phenolic biocides, it could be counterproductive in terms of its effects, because chlorinated chemicals in particular are the subject of intense opposition from groups such as Greenpeace.
1.5 Conclusion
There is evidence, therefore, of a failure to secure the advantages of harmonization of the regulation of biocides. The BPD is also reflective of the priorities of the “vanguard” states in Europe, particularly the members of the Nordic Council. The Common Principles for reviewing and authorizing biocides were developed by the Danish Environmental Protection Agency [50]. The Netherlands played a similar lead role in developing the measures to implement the Regulation on the evaluation and control of the risks of existing substances (EC793/93) covering high production volume (HPV) chemicals [54]. But the Biocides Directive (98/8/EEC) implements the substitution principle, which requires that products should no longer be authorized for use if there is in existence an alternative product less harmful to human health and the environment. This was first developed in Sweden as part of its “Sunset Program” in 1991 [55], and it subsequently sought to have it adopted in the OECD chemicals program approach to existing chemicals [56]. It is one of several ways in which Sweden and its Nordic Council allies have sought to “harmonize” EU chemicals policy to its own [57]. The dangers of substituting one substance for another without considering carefully any problems which might arise as a result are exemplified by the case of detergents containing phosphates, which contributed to eutrophication of waterways, often resulting in toxic algal blooms. Environmentally conscious industry and consumers in the 1980s were quick to move to new “green” detergents, but in 1996 Bryn Jones, the former head of Greenpeace in the United Kingdom, who led the worldwide campaign by for a phase-out, admitted it had been a mistake, with the substitution for phosphate detergents causing more problems than they solved. The German company Henkel developed phosphate substitutes – such as zeolites and polycarbonates – and licensed them internationally, but they caused rivers to foam in Switzerland where phosphates had been banned and possibly exacerbated algal blooms because of their toxicity for Daphnia water fleas which ate algae and thus helped prevent algal blooms. Another example of substitution without adequate risk assessment provides an even more salutary lesson: CFCs were developed in 1928 as substitutes for inflammable and noxious refrigerants [58]; their threat to the ozone layer was not identified until 1974. 1.5
Conclusion
The regulation of biocides has historically been of less salience than that of agricultural pesticides, but has come more to the fore as progress has been made on agricultural products, and attention has turned to smaller volume chemicals. As we have seen in this chapter, regulation of chemicals generally is affected by numerous political, social, and economic factors, and, in turn, has consequences
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1 The Political, Social, and Economic Framework
for these factors. Regulation is not just driven by concerns over efficacy or safety, but by the economic impact of regulation, which always creates winners and losers, at the company or national levels. This is a consideration which is made all the more important by the importance of intellectual property in the chemical industry. Patents are a form of licensed limited monopoly, and restrictions on competing products which are out of patent can enhance their value. Regulation of biocides also impacts by raising the costs of keeping existing products on the market and has helped assist the withdrawal of several active substances. It advantages companies which are global in character and products which enjoy larger markets, because registration costs can be recovered more readily in these circumstances. Much of the political concern the chemical industry has faced has been the result of concern over the size and power of the transnational corporations which dominate the industry. The biocides sector has traditionally seen a much more fragmented industry structure, but ironically the recent moves to increase regulation in most jurisdictions are likely to accentuate capital concentration in the sector. Different approaches have been taken in the US and the EU, and this has meant that the later EU regulation under the Biocidal Products Directive has been more costly than it might have been if harmonization of regulatory approaches had been achieved. Chemical regulation must reflect risk evaluations which vary from one situation to the next, and this poses a dilemma, since it makes sense for variation to exist in risk regulation between jurisdictions as risk-benefit calculations vary. This creates opportunities for national differences in regulatory approaches to be exploited for economic advantage. The Biocidal Products Directive has placed new demands on chemical testing. As we have seen, this is but one stage in the risk-management process which must inevitably involve the consideration of political, social, and economic factors, as well as the science of toxicity. But the rise in importance of ethical concerns, as evidenced by the rise of the animal rights lobby, has made even science a subject of increasing politicization.
References
References
[1] C. Hume, S. K. Moore, European Directive Will Push Up Costs, Chemical Week. 1999, September, 46. [2] OECD, Pesticide Programme Biocides – Non-agricultural Pesticide: A Report of the Survey of OECD Member Countries’ Approaches to the Regulation of Biocides Environmental Health and Safety Publication (No. 9 in Series OECD Pesticides Publications); 1999, June.
[3] L. N. Davis, The Corporate Alchemists: The Power and Problems of the Chemical Industry, Temple Smith, London, 1984. [4] B.G. Rueben, M.L. Burstall, The Chemical Economy, Longman, London, 1973. [5] G. C. Hufbauer, Synthetic Materials and the Theory of International Trade, Duckworth, London, 1966.
References [6] E. de Ghellinck, The Chemical and Pharmaceutical Industries, in The European Challenge, ed D.G. Mayes, Harvester Wheatsheaf, London, 1992. [7] W. Grant, W. Paterson, C. Whitston, Government and the Chemical Industry: A Comparative Study of Britain and West Germany, Clarendon Press, Oxford, 1989. [8] W. S. Comaner, The Political Economy of the Pharmaceutical Industry, Journal of Economic Literature. 1986, 24, 1178 – 1217. [9] R. Carson, Silent Spring, Houghton Mifflin, Boston, 1962. [10] M. K. Tolba, O. A. El-Kholy, The World Environment 1972 – 1992: Two Decades of Challenge, Chapman & Hall/UNEP, London, 1992. [11] L. Young, S. Ram Rao, S. G. Cort, Industry Corner: The Pesticide Market and Industry: A Global Perspective, Business Economics. 1996, 31(1), 56 – 61. [12] G. Lloyd, The Biocides Directive and Innovation: A Model of Over-Regulation? Paper presented at the joint European Commission CEFIC conference The Impact of New Regulatory Requirements on the Chemical Industry and its Competitiveness, Brussels, 2000, 5 October. [13] P. Shrivastava, Bhopal: Anatomy of a Crisis, Ballinger, Cambridge, Mass., 1987. [14] F. M. Bordewich, The Lessons of Bhopal: The Lure of Foreign Capital is Stronger Than Environmental Worries, Atlantic Monthly. 1987, March, 30 – 34. [15] P. Reiter, From Shakespeare to Defoe: Malaria in England in the Little Ice Age Emerging Infectious Diseases. 2000, 6(1), January–February. [16] K. Reichelderfer, M. Kuwano Hinkle, The Evolution of Pesticide Policy, in The Political Economy of US Agriculture, ed C. S. Kramer, Washington, D.C., Resources for the Future, 1989. [17] R. Boardman, Pesticides in World Agriculture: The Politics of International Regulation, New York, St Martin’s Press, 1986. [18] R. L. Paarlberg, Managing Pesticide Use in Developing Countries, in Institutions for the Earth: Sources of Effective International Environmental Protection, eds P. M. Haas, R. O. Keohane, and M. A. Levy, Cambridge, Mass., MIT Press, 1993.
[19] M. J. Dobson, Contours of Disease and Death in Early Modern England, Cambridge, Cambridge University Press, 1997. [20] B. N. Ames, R. Magaw, L. Swirsky Gold, Ranking Possible Carcinogenic Hazards, Science. 1987, 236 (17 April): 271 – 280. [21] S.S. Epstein, The Politics of Cancer, Sierra Club Books, San Francisco, 1978. [22] E. S. Mintzer, C. Osteen, New Uniform Standards for Pesticide Residues in Foods, Food Review. 1997, 20(1), 18 – 27. [23] National Academy of Sciences Regulating Pesticides in Food: The Delaney Paradox, National Academy Press, 1987. [24] T. Colborn, J. Peterson Myers, D. Dumanoski, Our Stolen Future: Are We Threatening Our Own Fertility, Intelligence, and Survival? A Scientific Detective Story, ed E. P. Dutton, New York, 1996. [25] B. Wynne, Risk Management and Hazardous Waste: Implementation and the Dialectics of Credibility, Springer-Verlag, Berlin, 1987. [26] M. Douglas, Risk and Blame, Routledge, London, 1992. [27] D. Krewski, P. L. Birkwood, Risk Assessment and Risk Management: A Survey of Recent Models, in Risk Assessment and Risk Management, ed L. Lave, Plenum Press, 1987. [28] J. D. Graham, J. Kassalow Hartwell, The Risk Management Approach, in The Greening of Industry: A Risk Management Approach, eds J. D. Graham and J. Kassalow Hartwell, Harvard University Press, Cambridge, Mass., 1997. [29] T. O. Tengs, M. E. Adams, J. S. Pliskin, D. G. Safran, J. E. Siegel, M. C. Weinstein, J. D. Graham, Five-Hundred Life-Saving Interventions and Their Cost-Effectiveness. Risk Analysis, 1995, 15(3), 369 – 390. [30] R. J. Zeckhauser, W. Kip Viscusi, The Risk Management Dilemma, Annals of the American Academy of Political and Social Sciences. 1996, 545, 144 – 155. [31] S. L. Brown, Harmonizing Chemical and Radiation Risk Management Environmental Science and Technology. 1992, 26, 2336 – 2338. [32] R. Brickman, S. Jasanoff, T. Ilgen, Controlling Chemicals: The Politics of Regulation in Europe and the United States, Cornell University Press, Ithaca, NY, 1985.
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1 The Political, Social, and Economic Framework [33] B. Fischoff, S. Lichtenstein, P. Slovic, S. Derby, R. Keeney, Acceptable Risk, Cambridge University Press, New York, 1981. [34] S. Jasanoff, Risk Management and Political Culture, Russell Sage Foundation, New York, 1986. [35] J. V. Rodricks, Calculated Risks: Understanding the Toxicity and Human Health Risks of Chemicals in Our Environment, Cambridge, Cambridge University Press, 1992. [36] C. Anderson, Cholera Epidemic Traced to Risk Miscalculation, Nature. 1991, 354, 255. [37] P. H. Barnes, Conflicting Notions of Risk: The Chasm of Conflict Between Institutional Regulators and the Public, in Integrated Risk Assessment: Current Practice and New Directions, eds R. E. Melchers and M. G. Stewart, Balkem, Rotterdam, 1995. [38] S. Beder, Global Spin: The Corporate Assault on Environmentalism, Scribe, Melbourne, 1997. [39] R. G. Noll, Reforming Risk Regulation, in Annals of the American Academy of Political and Social Sciences, 1996, 545, 165 – 175. [40] G. E. Schweitzer, Toxic Chemicals: Steps Towards Their Evaluation and Control, in Environmental Protection: The International Dimension, eds D. A. Kay and H. Jackson, Allanheld, Osmun, Totowa, NJ, 1983. [41] D. Robertson, A. Kellow, Globalisation and the Environment: Risk Assessment and the WTO, Edward Elgar, Aldershot, 2001. [42] H. Somsen, The European Union and the OECD, in Greening International Institutions, ed J. Werksman, Earthscan, London, 1996. [43] OECD, The OECD Chemicals Programme, OECD, Paris, 1993. [44] G. E. Schweizter, Borrowed Earth, Borrowed Time; Healing America’s Chemical Wounds, Plenum Press. New York, 1991. [45] C. Mensah, The United Nations Commission on Sustainable Development, in Greening International Institutions, ed J. Werksman, Earthscan, London, 1996.
[46] J. Brown, EU Restricts Chemical Imports, Chemical Week. 2000, 1 November. [47] A. Scott, IMO Agrees on Tributyl Tin Ban, Chemical Week. 1999, 8 December. [48] H. Tilton, Biocide Makers Deep in Regulatory Waters; Chemical Marketing Reporter. 1989, 24 April. [49] R.Westervelt, Biocide Market Pared Down by Environmental Regulations: Producers Look Overseas to Maintain Margins, Chemical Week. 1994, 27 July. [50] R. Begley, E. Chynoweth, Pesticide Registration: High Anxiety in the US and Europe: EPA Cries Poor Again While EC Starts Its Program, Chemical Week. 1992, 9 September. [51] D. Knight, Active Control for Biocides, Chemistry and Industry. 2000, 7 August. [52] K. Walsh, S. K. Moore, European Directives Will Kill Some Actives, Chemical Week. 1998, 21 October. [53] K. Walsh, S. K. Moore, European Directives Will Kill Some Actives, Chemical Week. 1998, 21 October. [54] P. McCutcheon, Risk Management of Chemical Substances in the European Union, in The Politics of Chemical Risk: Scenarios for a Regulatory Future, eds R. Bal and W. Halffman, Kluwer, Dordrecht, 1998. [55] Swedish National Chemicals Inspectorate and Swedish Environmental Protection Agency, Risk Reduction of Chemicals, KEMI Report No 1/91, 1991. [56] A. Kellow, International Toxic Risk Management: Ideals, Interests and Implementation, Cambridge University Press, Cambridge, 1999. [57] R. Nillson, Integrating Sweden into the European Union, in The Politics of Chemical Risk: Scenarios for a Regulatory Future, eds R. Bal and W. Halffman, Kluwer, Dordrecht, 1998. [58] D. L. Downie, UNEP and the Montreal Protocol, in International Organizations and Environmental Policy, eds R. V. Bartlett, P. A. Kurian and M. Malik, Greenwood Press, Westport, 1995.
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2
The Biocides Market Patricia Martin
2.1
Introduction
Wherever there is a source of nutrition and moisture micro-organisms, such as bacteria, viruses, algae, moulds, and yeasts, will grow, even in extreme climatic conditions. The growth of these micro-organisms may impact on human health by causing spoilage of food products. Alternatively, they may interfere with manufacturing processes by causing rot or slimes to form or by blocking valves and pipes. Man’s principal defence against these micro-organisms is the use of a biocidal product. Biocidal products are supplied in a wide variety of forms and range from the inexpensive bulk commodity chemical material to the high-priced niche formulation designed to target a specific micro-organism(s). There are a number of chemical classes of material which comprise today’s biocidal products, and these are marketed with distinct efficacy (or performance) profiles against a range of micro-organisms. What this range of biocidal products has in common is the ability to kill (or control the proliferation of) these deleterious micro-organisms under a given set of conditions. It is this property which makes biocidal products commercially viable in the divergent global environmental marketplace.
Definitions
In the European Community (EC) legislation, within the body text of the Biocidal Products Directive (98/8/EC), there is a rather complex definition of a biocidal product [1]: Active substances and preparations containing one or more active substances, put up in the form in which they are supplied to the user, intended to destroy, deter, render harmless, prevent the action of, or otherwise exert controlling effects on any harmful organism by chemical or biological means. The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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2 The Biocides Market
A “harmful organism” is further defined as: Any organism which has an unwanted presence or a detrimental effect for humans, their activities or the products they use or produce, or for animals, or for the environment. The situation regarding regulation of those products which by chemical (or biological) means prevent the adverse effects of micro-organisms (or control pests) in Europe and the parallel regulation of plant protection products (which are commonly referred to as pesticides) is somewhat different to the legislative regimes which exist in the United States of America. Here regulatory control of both crop and noncrop protection products is administered by the USA Environmental Protection Agency (EPA) Office of Pesticide Programs (OPP). However, in the USA noncrop pesticides or biocidal products are usually referred to as antimicrobial pesticides. Antimicrobial pesticides, such as disinfectants and sanitizers, are pesticides defined in the USA legislation as being those that are intended to: *
*
disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms, or protect inanimate objects (for example, floors and walls), industrial processes or systems, surfaces, water, or other chemical substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, algae, or slime.
The USA definition does not include certain antimicrobial pesticides intended for food use, nor does the legislation apply to personal health care disinfectants, which are regulated as “drugs” under the Food and Drugs Administration (FDA). Thus, there is likely to be continuing confusion and uncertainty for global suppliers of these biocidal products with respect to which regulatory authority has to be adhered to. The major determinants are: * *
the end-use application of the antimicrobial/biocidal product, and the specific nation for which the biocides will be marketed.
It appears that despite the recent efforts of the Organization for Economic Cooperation and Development (OECD) on various aspects of harmonization [2], there is still some way to go before the major countries/trading blocks are prepared to compromise and set a uniform standard to ensure mutual acceptance of data packages for the prior approval of biocidal products on a global basis.
2.1 Introduction
2.1.1
EC Market: End-use Applications
According to the EC Directive (98/8/EC) the biocidal products industry may usefully be considered as being composed of four major areas with some 23 different product types encompassed therein. These are further illustrated below: *
*
*
*
Main area 1: Disinfectant and general biocidal products Product Type: (1) Human hygiene biocidal products (2) Private area/Public health area disinfectants and other biocidal products (3) Veterinary hygiene biocidal products (4) Food and feed area disinfectants (5) Drinking water disinfectants Main area 2: Preservatives Product Type: (6) In-can preservatives (7) Film preservatives (8) Wood preservatives (9) Fiber, leather, rubber; and polymerized materials preservatives (10) Masonry preservatives (11) Preservatives for liquid-cooling and processing systems (12) Slimicides (13) Metal working-fluid preservatives Main area 3: Pest control Product Type: (14) Rodenticides (15) Avicides (16) Molluscicides (17) Piscicides (18) Insecticides, acaricides, and products to control other arthropods (19) Repellents and attractants Main area 4: Other biocidal products Product Type: (20) Preservatives for food or feedstocks (21) Antifouling products (22) Embalming and taxidermist fluids (23) Control of other vertebrates
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2 The Biocides Market
Despite the above categorization and the statement in the body text of the Directive (98/8/EC) which specifically excludes products which are covered under the scope of other existing Community legislation, there remain a number of “gray areas” yet to be finally resolved to allow suppliers to understand if their products are in, or out of, scope of the Biocidal Products Directive and hence strive for compliance with this legislation. It is understood that the EC Commission may document decisions on scope issues in a written form similar to the “Manual of Decisions”, which is associated with the notification of new substances legislation [3] under the 7th Amendment to the Dangerous Substances Directive (67/548/EEC).
2.2
EC Market: Consumption of Biocidal Products by End Use
The following data relates to the use of specialty biocides and excludes commodity chemical data on substances such as chlorine and hypochlorite. The latter chemicals have many other functionalities besides that of antimicrobial use. According to a survey conducted by the Biocides Information Services [4], the western and central European consumption of specialty biocides was in excess of US $ 850 million at manufacture level during 2000. Figure 2.1 illustrates the divisions by main end-use application area. As might be expected, the single largest end use in western and central Europe for biocidal products is that related to wood preservation and timber treatment applications. This is coincidentally also the product type with the greatest existing controls legislation in a number of member states governing the use of these treated products
Fig. 2.1. European consumption of specialty biocidal products by main end-use application for the year 2000
2.3 Global Market: Consumption of Biocidal Products by Geographical Region
and is therefore expected to be an application area where industry have a wealth of both hazard and exposure data. For these reasons, primarily, this product type, (PT8), formed the first of two end uses to be called in under the First Review Regulation [5], the other being rodenticides, (PT14), which were formerly controlled under crop pesticides legislation in the majority of EC Member States with existing laws. The European market for biocidal products in 1999 – 2000 was valued at some US $ 850 million by various international marketing consulting companies, including Frost and Sullivan [6]. The latter forecast a total market revenue rise to US $ 984 million by 2006 with a compound annual growth rate of some 2.1 %.
2.3
Global Market: Consumption of Biocidal Products by Geographical Region
It has been variously estimated that the global consumption of biocidal products in recent years accounts for some US $ 3200 – 3500 million. The single largest consumer is undoubtedly the North American region (43 %) with Europe (ca. 27 %) being the second largest consumer [4]. An illustration of the global market consumption by regions is given in Figure 2.2. According to figures released by the market research company, Directed Research/ Agricultural Information Services (DR/AIS), noncrop pesticides or biocidal products constituted some 12 % of the global pesticide market for active substances (AIS) at manufacturer level in 1997 [7]. DR/AIS has been tracking the use of biocidal products since 1992 and ascertained that this area was the fastest growing of all pesticide segments, and during the period 1995 – 1997 it actually achieved an average growth rate of almost 4 % (excluding the flower and over-the-counter home and garden market uses). Within Western Europe it is generally accepted that the demand for industrial biocides, based upon country or region is led by Germany (ca. 25 % market). The United
Fig. 2.2.
Consumption of biocidal products by geographical region
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2 The Biocides Market
Kingdom, France, and the Nordic countries (Denmark, Finland, Norway, and Sweden) are the second largest markets (15 %), followed by Italy (9 %), then the Benelux countries (8 %) together with Spain and Portugal (8 %), and finally Austria, Ireland, Greece, and Switzerland (4 %). According to a report from the Freedonia Group [8], global demand for biocidal products is forecast to increase 5.6 % p. a. to US $ 5.8 billion in 2004 (statement issued in early 2001). North American demand is expected to grow by 5 % p. a. to US $ 2.6 billion with Western Europe markets growing by a similar rate to US $ 1.4 billion and usage in Asia Pacific increasing at the rate of 6.8 % p. a. to US $ 1.2 billion. Demand from the rest of the world is expected to grow at 6.7 % p. a. to US $ 580 million.
2.4
Supply Chain for Biocidal Products
The European biocides industry is a highly varied assortment of small businesses. The introduction of the Biocidal Products Directive (98/8/EC) brings into focus, probably for the first time for many, the wide ranging potential problems which might adversely affect our domestic lifestyle and health, as well as industrial products and processes, caused by the effects of “pests” ranging from micro-organisms to mammals. This variety of causative agents leads to the supply of counteracting products, biocidal products, to effect control of these pests from a highly fragmented, but often highly specialized industry. The biocidal products industry operates globally to deliver its products and services from manufacture to end user by way of a supply chain that might usefully be categorized into three distinct groups as listed below: * * *
active-ingredient manufacturers formulators of biocidal products/service companies distributors.
The manner in which the supply of biocidal products reaches the market is illustrated in Figure 2.3.
2.4.1
Active-ingredient Manufacturers
These companies manufacture the substance(s), which have the ability to kill or otherwise control deleterious micro-organisms or affect pest control. Data to evaluate the potential health, safety, and environmental effects of these substances as well as their
2.4 Supply Chain for Biocidal Products
Fig. 2.3.
Supply chain scenario for the biocides industry
efficacy are collected as part of the costs for developing and marketing the active substances. It is seldom the case that companies involved in the biocides industry act solely as manufacturers of active ingredients, more often than not they are also involved in formulation of the specialty biocidal products for the various end-use applications. Active-ingredient manufacturers’ major route for supply is direct sales to companies that prepare formulations, the formulators or service companies. This route probably accounts for up to 60 % of their distribution. In addition, they may sell the active ingredient direct to the end user and/or use distributors. Both routes are likely to account for some 20 % each of the supply chain movement for active ingredients. The leading active-ingredients manufacturers include companies such as: Akzo Nobel, Arch, Avecia, Bayer, BASF Microcheck, Ciba, Clariant, Dow, Great Lakes, Lonza, Rohm and Haas, and Troy.
2.4.2
Formulators/Service Companies
The strengths of this component of the supply chain for biocidal products are intimately related to their customer-care approach to problem-solving and the provision of on-site services. Using these attributes has enabled the formulators to achieve a significant market penetration for their custom-based products based upon the active ingredients purchased. The formulator is able to put together specific customerblends, at relatively low costs, to meet niche requirements.
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The know-how and skills of providing these formulated products (with often a broader spectrum of micro-organism(s) control) to meet specific end-user requirements afford the formulator the opportunity to pass on a significant charge for the product and service in excess of the cost of the ingredients in the biocidal formulation. The leading formulators include such companies as: Buckman, Creanova, DiverseyLever, Ecolab, Henkel, Hercules BetzDearborn, Nalco, Rentokil, Suez Lyonnais des Eaux, Sanitised, and Schulke and Mayr.
2.4.3
Distributors
Distributors are the “middlemen” in the supply chain acting as agents for both the active-ingredient manufacturer and the formulator to enable speedy and competitive delivery of, often small, volumes of biocidal products to end-use customers globally. The distributor is a popular means for supply since they tend to market a range of chemical additives to end users and are often already involved in a supply chain relationship outside of the biocides industry. Simply adding biocidal products onto an already existing delivery schedule enables the distributor to be competitive. The leading distributors for biocidal products include: Ashland, Brenntag, Biesterfeld, Ellis and Everard, Kloeckner, Quimidroga, and Univar.
2.5
“Key Drivers” for Market Development
Undoubtedly the paramount influence on the European biocides market for the next ten-years or so will be the Biocidal Products Regulation and any associated “daughter” legislation. The principal impacts of the legislation are expected to be: *
*
*
*
Reduction in product development activity Associated with the increased costs for registration and leading to fewer new products on the market. Not all the currently listed “active substances” presently available will be subsequently “approved” and be listed in Annex 1 (1A) Support through the “approval” procedures will depend upon “profitability” and willingness of manufacturer (and others) to fund data collection. Registration/approval processes favor large companies Large companies expected to be “data-rich”. Expected changes include extension of existing product range to new applications and to new formulations.
2.5 „Key Drivers“ for Market Development *
Expected changes include further company mergers and/or acquisitions and divestments from noncore activities.
A conservative estimate of expected growth of the European biocide industry is some 2 % per year up to 2005 [4]. A number of factors will impinge on this forecast and include: * * * * * *
developing countries population demographics “safer” alternatives technological change awareness of “hygiene” new uses.
Developing Countries – the use of biocidal products is likely to increase in concert with rising living standards. It may also be expected that there will be a fundamental change away from the older active ingredients, such as the organochlorine chemicals, in these areas as they are progressively phased-out in other more developed regions based, hopefully, on a thorough assessment of risk rather than simply their intrinsic hazardous properties. Population Demographics – people are retiring earlier and/or have more leisure time, and with this there will be an expected increase in leisure time and activities. It is expected that “the gardening population” will significantly increase, and hence use of biocidal products associated with this pursuit. “Safer Alternatives” – some traditional biocidal active ingredients are already being “substituted” as the result of other legislative pressures i.e. ban on the use of mercurials, pentachlorophenol, and triorgano tin compounds. These bans and other prospective restrictions on the marketing and use of the “older” biocidal products, as a result of their risk assessment under the new Directive (98/8/EC) will lead to less choice for the end user. Technological Change – the most obvious example is in the shift away from solventbased paints to aqueous-based systems over the last ten years as a result of the hazards associated with solvent-neuropathies perceived to be caused as a direct result of (chronic) inhalation exposure (or dermal contact) to the off-gases – known as volatile organic carbons (VOCs). “Hygiene” Awareness – over the past three to five years, the use of biocidal products as hygiene aids in household products, personal care, and textiles has escalated aided by media presentations. Hardly any member of the shopping public can have failed to observe the upsurge in advertising associated with products marketed under the MICROBAN name in the general grocery and supermarket chains. Despite the claims
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2 The Biocides Market
made, the active ingredient, a chlorinated phenolic compound, is not all that efficacious against certain commonly occurring bacterial pathogens found in various domestic environments. It seems the public are not interested in “efficacy” per se, if that means they loose out on available products, which provide at least some degree of perceived “safety” with respect to actions against unwanted micro-organisms. New Uses – human research and innovation proceeds in line with the quest for sustainability of finite resources at the same time as re-use/recycling continues, and, as part of this evolutionary process the use of biocidal products, to address these new situations, will abide as new applications and end uses demand. New, or novel, biocidal active ingredients are unlikely to be at the forefront of the research and development plans of many global companies due to the high costs associated with gaining entry to the market (especially in the EC with the Biocidal Products Directive) and the relatively long recovery times for recouping these costs. The volumes of supply of biocidal active ingredients are coupled to the low inclusion levels in the formulated products, and hence the time to recover initial development costs (and associated hazard and efficacy data) can be greater than ten years, by which time there will be no data protection. Second suppliers, “me too” products, can enter the market place with none of the development costs of the original developer/manufacturer.
2.6
History and Current Trends 2.6.1
European Community
The first step in the EC towards a comprehensive regulatory framework for biocidal products was initiated in 1991 when an “early unofficial” draft [9] of a proposed Biocidal Products Directive appeared and this was subsequently followed in 1993 by the official first proposal [10]. The premise of the European Commission in 1993 was to establish a single European market in biocidal products by the introduction of a harmonized authorization scheme based upon the assessment of risks to humans and the environment, coupled with a consideration of efficacy. Before the introduction of the Biocidal Products Directive (98/8/EC), the European market for these products was something of a “jig-saw” insofar as being able to identify those member states with any forms of regulation, and which particular end uses this applied to, prior to being able to supply products to customers. A variety of regulatory practices were utilized in the various member states, and these were reviewed under an OECD initiative in 1997 using a questionnaire survey
2.6 History and Current Trends
approach [2]. It appeared that those countries surveyed had an approval system for wood preservatives, and most also had a system for products used in vertebrate and invertebrate pest control (specifically for rodenticides, repellents, and insecticides/acaricides for direct use on humans, clothes, and/or pets). In the UK, the only legislation covering biocidal products prior to enactment of the EC Directive (98/8/EC) into UK law was that of the Control of Pesticides Regulations (COPR) 1986, and this covered wood preservatives, public hygiene insecticides, masonry biocides, and antifouling paints. Approval schemes administered by other authorities in the UK did consider the nature and properties of the chemicals to be used in areas such as, for example, swimming pools and off-shore applications. The Biocidal Products Directive aims to ensure harmonization of the European market for biocidal products and their active substances and at the same time will guarantee a high level of protection for humans and the environment. This harmonization of the internal market is likely to be of more immediate benefit to those industries where controls already exist. However, the removal of the barriers to trade will not be at the expense of lowering health or environmental protection. The Directive will work by ensuring that only those biocidal products which contain an active ingredient(s) listed in Annex I of the Directive will be authorized for use. In parallel with the Directive, the Commission will be utilizing various other legislative instruments, such as Regulations, to require Industry to submit data on “existing active ingredients” over a ten year timetable. The first of these Regulations [5] “called in” data for all active ingredients used as wood preservatives and rodenticides for evaluation at Commission level and possible inclusion in Annex I. During the intervening period of this evaluation, existing national rules in the various member states continue to apply to any biocidal product containing an existing active ingredient until such time as it is listed in, or refused listing in, Annex I. Once an active ingredient is listed in Annex I, biocidal products containing this active substance may be authorized for marketing at individual member-state level by the national competent authorities. Once a product is authorized in the first member state it will be possible for it to be mutually recognized and hence authorized by other member states. Despite the laudable aims of the introduction of the Directive, which are supported by the European biocides industry, there are still doubts about the implementation and running of this very complex legislation being voiced even at this late stage by the industry. Consistently the biocides industry has stated that the Directive will seriously inhibit innovation. Industry has illustrated this concern by reference to the following facts [11] gathered against the background of the current nonharmonized schemes for biocidal products in existence across the member states:
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* *
one to two new active ingredients for biocidal products per year in the EC (22 new active substances since 1984 in the USA) seven to eight new active molecules for plant protection products 250 new industrial chemicals per year in the EC.
According to an industry spokesperson, the Directive is likely to replace the USA EPA as the “major hurdle” to worldwide research on new biocides [12]. The European Chemical Industry Federation, CEFIC, believes that few, if any, companies will carry out targeted speculative research on new biocide active substances in the near future, and thus it is difficult not to envisage that the already low rate of innovation in this area will become even lower. According to the EC Commission, the introduction of the Directive in this area was the “simplest legislative instrument and also the least costly [option], which ensures a high level of health and environmental protection” [13]. The EC Biocides Industry has always disagreed on this aspect related to industrial competitiveness and at open meetings have given examples to attempt to provide an insight for the regulators and the public of the real costs associated with this Directive. There can be little doubt among industry and regulators that the Directive will significantly increase the costs of compliance as a consequence of the following expenses: * * * * *
regulatory studies, eco-/toxicology, environmental fate efficacy studies dossier preparation competent authority review charges legal costs for forming/running task forces
Industry will pass these additional costs on to the European consumer of these biocidal products as they do not have the necessary resources available to absorb the costs involved. An “average” EC manufacturer of active ingredients for specialty biocidal products is likely to have an annual turnover of less than ECU/euro 20 million (ca. US $ 17.5 million) generated from the sales of eight active substances in a total market of between ECU/euro 300 – 500 million (ca. US $ 260 – 440 million) p.a. [11]. The annual profit, some ECU/euro 2.5 million (ca. US $ 2.2 million) per company (based on 30 companies) is less than the predicted costs for compiling the data set for one existing active substance, ECU/euro 2.8 – 4.2 million (ca. US $ 2.5 – 3.7 million). Thus it is not difficult to visualize the impact on innovation. During the ten year review period (assuming that the active ingredient is not called-in “early” via a Regulation) the “average” EC manufacturer of active ingredients for specialty biocidal products will have a maximum income of less than ECU/euro 200 million (ca. US $ 175
2.6 History and Current Trends
million). If the average investment in research and development is say 5 % of income, then this equates to some ECU/euro 10 million (ca. US $ 8.8 million). ECU/euro 10 million (ca. US $ 8.8 million) would only support three to four active substances, and yet the “average EC manufacturer” needs to support twice that number of active-ingredient materials before considering investment in new novel active-ingredient chemistries!
2.6.2
United States of America
The system administered in the United States by the Environmental Protection Agency (EPA), commonly known as the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), has been in situ for a number of years and has both similarities and differences, in approach and application, for the control of biocides to that now proposed in the EC. FIFRA registration procedures apply to both crop and noncrop pesticides. The EC Biocides Industry had hoped that the regulators, when considering harmonization of legislation for the control of biocidal products in the EC, would look to improve on, and learn from, the experiences of the operation of the FIFRA process. Following minor revisions to the FIFRA registration process in 1984 with significant revisions in 1988 (see later chapter for greater detail) which required the intervention of the President, the EPA saw a substantial increase in its workload, and with that a realization that the review procedures (and re-registration) would not be completed until sometime after the nine year period allowed for by the changes in the law. At the start of this FIFRA process, there were approximately 420 active ingredients classified for use in noncrop pesticides, however as the review program began to take effect this number was reduced to 261. The EC biocides industry was therefore rightly concerned that if the significant resources available to the EPA were strained by review of 261 active substances, then it does not take a mathematical genius to comprehend the difficulties likely to be faced by the EC Commission and the national competent authorities with respect to the >900 active substances on the European list. The costs to US industry for the FIFRA ’88 program were estimated at £ 225 million; recently the EPA informed registrants that the funds were nearly used up and requested industry to contribute additional funds to this re-registration procedure. Again, this must raise doubts for the European biocides industry and their ability to fund the newly introduced legislation especially when one considers that there have been a number of measures introduced in the US legislation to streamline the process and keep costs commensurate with likely exposure and risks, such as:
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2 The Biocides Market * *
a “tiered approach” for the submission of hazard data efficacy data only required with the dossier for those products used to control pests, which pose a threat to health.
Such measures have not been forthcoming with respect to the development and implementation of the Biocidal Products Directive, despite all the scientific and commercial presentations from industry since 1991. Indeed the recent Commission White Paper on a future chemicals policy [14] is at odds with this Directive. The White Paper advocates a “tiered approach to testing” commensurate with risk and it also seeks to promote innovation and competitiveness of the EC industry. How then does the Commission reconcile their proposed strategy with Directive 98/8/EC?
2.7
Impact of New Legislation
The introduction of the Biocidal Products Directive in Europe will undoubtedly lead to the loss of the small- and medium-sized enterprises/companies (SMEs), which until now have been responsible for many of the formulations on the European market supplied into niche application areas. The costs for generation of the EC dossier required to register these small volume products will be prohibitively expensive for the SMEs. However, there may be a glimmer of hope afforded in the legislation if the following concepts are utilized: * * *
low-risk products frame formulations task forces.
Low-Risk Product – is one which under the conditions of use is considered to pose only a low risk to humans, animals, and the environment and contains as active substance(s) one or more of those listed in Annex 1A of the Directive and does not contain any substance(s) of concern. The legislation instructs that decisions on low-risk products will be made within 60 days, and that they will be “registered” on receipt of a simplified dossier containing the following elements: * * *
applicant details identity of the biocidal product intended uses
2.7 Impact of New Legislation * * *
efficacy data analytical methods classification, packaging and labeling data, and a safety data sheet
Frame Formulation – is considered to be a “specification” for a group of biocidal products having the same end-use and user type. These products contain the same active substance (not necessarily purchased from the same manufacturer, but at least the active substance must have the same product/chemical specification). This concept of frame formulations is similar to the proposal introduced by the EPA for the “Clustering of Products” following the 1988 review of FIFRA to facilitate the increased workload associated with the re-registration process. In PR Notice 88 [15], Clustering of Quaternary Ammonium Compounds, the EPA placed all 211 registered quaternary (“quats”) ammonium compounds classified as active substances into one of four groups depending upon the alkyl chain length and the percentage carbon distribution within the chain. The frame-formulation concept allows for small variations in the composition of the chemical substances present in a frame formulation provided: * *
these variations do not affect the level of risk, nor affect the efficacy of the product.
For example, the legislation allows for: * * *
a reduction in the percentage of the active ingredient, and/or a variation in the percentage of nonactive substances, and/or the replacement of colors and perfumes.
Under the existing terms of the draft Technical Notes for Guidance (Finland) [16], the process would then be: *
*
*
The “mother formulation” representative of many like-products would be authorized following assessment by the normal procedure. Subsequent formulations, from applicants with rights to the dossier of the “mother product”, and which are a “fit” for the frame concept, would only require a simplified dossier for submission and assessment. The “simplified” assessment dossier should lead to registration within 60 days.
The “ownership” of the dossier associated with the “mother product” and subsequent “frame groups” may rest with individual companies, groups of loosely associated companies, or may be more formalized under a Task-Force sharing agreement.
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Task Force (TF) – is essentially a coalition of competitor companies with a (hopefully) defined purpose: for example, achieving Annex I listing, under Directive 98/8/EC, for a specific active ingredient used in a number of different biocidal products marketed by the companies (or their supply chain contemporaries). The EC Directive does not contain any specific stated provisions on task forces, although it does encourage data sharing. Such alliances have worked successfully in the context of the re-registration of antimicrobials under the USA FIFRA legislation and also in Canada, and have prevented the unnecessary suffering of animals (by reducing duplicate testing) and thereby also saved the associated costs for these studies. Lately, TFs have been used in relation to the EC pesticides legislation under 91/ 414/EEC (17). Typically a document, often referred to as a “Memorandum of Understanding” [MoU] defines the purpose of the task force, names the member companies, and describes an agreed limit for the capital expenditure. A TF generally operates with at least two tiers: 1. a business/commercial committee, and 2. a technical-scientific/regulatory committee. The MoU should also incorporate the following parameters: * *
* *
* *
which end uses are to be defended define the provisions for late joining and early departure from the TF or “takeovers” between members the terms for the financial compensation for data already held by members the mechanism of cost-sharing for new studies i.e. based on market-share, equal share, or a combination thereof default provisions in the event of nonpayment by a member “ownership of the data” and its availability for use outside of the EC 98/8/EC provisions by members and/or affiliates
One also needs to keep the obligations of compliance with EC competition law paramount when considering setting up and entering into a task force arrangement. The EC competition law prohibits agreements or concerted practices amongst competitors, which may restrict competition (for example, agreements on pricing, territorial allocations etc.). In addition the legislation requires that there must be no exclusion of competitors from joining on equal conditions. Failure to comply with this EC legislation may result in a financial penalty, for each member of the task force, which may be up to 10 % of a company’s turnover.
References
2.8
Conclusions
The extensive cost of the Biocidal Products Directive to the EC biocides market will inevitably cause further slowing down in terms of both the research and development of innovative chemistries for new active ingredients. As a way of overcoming this, manufacturers and formulators will be forced to work together in a closer manner than perhaps hitherto to introduce new products onto the market, possibly by elucidating synergies between the dwindling supported active substances available on Annex 1, that have not yet been discovered. The supply chain will most probably consolidate, and we may see more mergers and acquisitions in a similar manner to that which has occurred over the past two years in the general industrial chemicals area. Some limited evidence in support of this is available with Clariant’s takeover of BTP and Rhodia’s acquisition of Albright and Wilson in March 2000. The formulators, under the CEFIC sector group, EPFP (European Producers of Formulated (Biocidal) Products), have already researched alternate suppliers for their active ingredients, and unless the Commission adopts further measures we may well see an explosion of non-EC manufactured biocidal products entering the market place. These imports can easily out-price domestic products as they do not have to be manufactured under the existing legislative strictures for human or environmental wellbeing that form the cornerstone of the European legislation. There is no doubt that the demand for biocidal products will continue to grow as the public and consumers awareness of the benefits of continued improvements in hygiene become ever more apparent. It is open to the biocides industry to successfully implement a strategy to develop these highly desirable products against a background of increasingly stringent legislative measures, and that probably is predicated on more openness and co-operation with other sectors of the supply chain.
References
References
[1] Directive 98/8/EC of the EU Parliament and Council of 16th February 1998 concerning the placing of biocidal products on the market. Official Journal publication L123, 24th April, 1998. [2] OECD Report to Pesticides Forum, 16 – 17 June, 1997. ENV/MC/CHEM/PEST/RD (97)3. Biocides/Nonagricultural pesticides: Preliminary results of the survey on the regulation of biocides in OECD member countries.
[3] Council Directive 92/32/EEC of 30th April, 1992 amending for the seventh time Directive 67/548/EEC on the approximation of the laws, regulations, and administrative provisions relating to the classification, packaging, and labeling of dangerous substances. Official Journal publication L154, 5th June, 1992. [4] Biocide Information Services (BIS), Ireland (2000). Personal communication from N D’Arcy concerning an executive summary of global biocides data, 2000.
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2 The Biocides Market [5] Commission Regulation 1896/2000 on the first phase of the program referred to in Article 16(2) of Directive 98/8 of the European Parliament and of the Council on biocidal products. Official Journal publication L228, 8th September, 2000. [6] Frost and Sullivan, Report: Strategic Review of the Impact of the European Biocidal Directive, 2000. [7] S. Watkins, World Nonagricultural Pesticide Markets; Agrow Reports publication, 2000. [8] Freedonia Group Report 1257, Biocides to 2004, 2000. [9] Proposal for a Council Directive of 1991 concerning the placing of nonagricultural pesticides and the active substances thereof on the market. Document XI/III/ 563/91. Brussels, 9th August, 1991. [10] Proposal for a Council Directive of 1993 concerning the placing of biocidal products on the market COM (93) 351 final–SYN 465 (27/7/93). Official Journal publication C239, Vol. 36, 3rd September, 1993. [11] B. Backhouse, M. Burt, Current Issues for Industry: Time for Reappraisal. Paper at the 1997 IBC International Conference on the Biocidal Products Directive, Brussels, 1997.
[12] B. Backhouse, Biocidal Products Directive 98/8/EC: Impact on Industry. European Safety Newsletter June/July, 1998. [13] European Commission, An Industrial Competitiveness Policy for the European Chemical Industry: An Example. COM (96) 187 final, Brussels, 30th April, 1996. [14] European Commission, White Paper: Strategy for a Future Chemicals Policy. COM(2001) 88 final, Brussels 27th February, 2001. [15] Pesticide Registration Notice PR Notice 88-2 Clustering of Quaternary Ammonium Compounds, EPA, 26-2-88. [16] Data Requirements for Biocidal Product Types, Project No. 96/720/3040/DEB/E2 Finnish Environmental Institute, Draft Proposal Version 4, June, 1999. [17] Council Directive 91/414/EEC of 15th July, 1991 concerning the placing of plant protection products on the market. Official Journal publication L230, 19th August, 1991.
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3
Regulatory Control of Biocides in Europe Derek J. Knight and Mel Cooke
3.1
Introduction
The biocides industry transformed dramatically with the implementation of the Biocidal Products Directive (BPD) [1]. The Directive took years to formulate and will impact on manufacturers, distributors, and users of biocides. The BPD is tougher than any prior legislation, either within Europe or in the rest of the world, and may cost the industry over £ 350 million. Active substance suppliers will have to co-operate with distributors to get biocidal products registered. The industry has serious concerns over the cost of testing of active substances, particularly if the full data specified in the BPD are needed in all cases. However, the data requirement issue is likely to be resolved, at least in part, through published guidance and also by precedent during the transitional period from national regulation of biocides to the European BPD (“learning by doing”). Industry must therefore invest in keeping up-to-date with regulatory advances as the authorities grow in experience and the state-of-the-art evolves. The BPD filled a gap that existed in current legislation of chemical substances, although some prior EU legislation had already been in force for some biocides: the Marketing and Use Directive [2] [76/769/EEC (as amended) restricting the marketing and use of certain dangerous substances]; the Dangerous Substances Directive [3] (67/548/EEC), and its 7th Amendment [4] (92/32/EEC) covering notification of new chemical substances and classification, packaging, and labelling of dangerous substances; and the Dangerous Preparations Directive [5] (Council Directive 88/379/ EEC, as amended) covering hazard communication of dangerous preparations. Belgium, Denmark, Finland, the Netherlands, Sweden, and the UK had systematic and comprehensive national controls of some types of biocidal products. The BPD harmonizes the authorization of biocidal products within each Member State, while the active substances are evaluated at EU level by the European Commission.
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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3 Regulatory Control of Biocides in Europe
3.2
The EU Biocidal Products Directive
3.2.1
History and Development
The European Commission first drafted legislation to answer the concern of the Council of Ministers that there was a lack of harmonized EU provisions for biocidal products, and to ensure a more uniform and higher level of health and environmental protection throughout the EU without compromising the internal market. Hence, on 27 July 1993, the Commission submitted a proposal to the Council for a Directive concerning the placing of biocidal products on the market. This initial proposal was amended by the Commission to satisfy European Parliament and Council opinion that guidance on risk assessment and authorization should be an integral part of the Directive. The Commission therefore submitted a revised version to the Council on 20 July 1995, which incorporated a set of Common Principles covering this as Annex VI to the Directive. The European Parliament and the Economic and Social Committee examined the proposed new Directive and delivered their opinions on 18 April 1996 and 27 March 1996, respectively. The Commission then forwarded a second amended proposal to the Council on 24 June 1996, culminating in the Council adopting its Common Position on the new Directive on 20 December 1996. After a second reading of this Common Position by the European Parliament and further consultations under the auspices of the Conciliation Committee to resolve remaining differences with the Commission and Council during 1997, a final text for the Directive was adopted by the Council and Parliament Decisions of 18 December 1997 and 14 January 1998, respectively. This Biocidal Products Directive [1], Directive 98/8/EC of the European Parliament and Council of 16 February 1998, was published on 24 April 1998 and entered into force 20 days thereafter. Each Member State appointed an agency to deal with the new legislation: the so-called competent authority. There was a two year period for the member states to transcribe the BPD into their own national legislation. Hence the scheme was scheduled to come into force in each Member State by 14 May 2000, although in practice this target date was not met in many countries. The BPD contains a timetable for the transition to the new authorization scheme, so existing national or other EU provisions continue to apply until the various aspects of the BPD come into force. The BPD is comparable to Plant Protection Products Directive [6] (Council Directive 91/414/EEC), and also incorporates principles already being used to assess chemical substances. The Directive itself had to be agreed by the Environment Ministers of all the member states. It also had to be agreed by the European Parliament, with directly elected
3.2 The EU Biocidal Products Directive
members from individual regions across Europe. Hence the Directive is a compromise between the various parties. It is also somewhat idealistic, in that some of the provisions are impractical and place unnecessary burden on European industry. Fortunately, however, the BPD gives the operation of the scheme to the European Commission and national competent authorities. There has been much debate amongst industry and the national competent authorities about how to operate the scheme, within the idealistic legal framework of the Directive. Some competent authorities themselves are considered by some to take an idealistic approach, whereas others are more pragmatic and give higher priority to the needs of industry and biocide users.
3.2.2
Scope of the Biocidal Products Directive
The BPD defines biocidal products as preparations containing one or more active substances that are intended to control harmful organisms by either chemical or biological, but not physical, means. This encompasses a wide range of products including disinfectants, insect repellents, and antifouling paints. Annex V of the BPD classifies biocidal products into four main groups: disinfectants and general biocides, preservatives, pest controls, and other biocides, which are further broken down into 23 separate categories (see Table 3.1). Table 3.1.
Products defined as biocides within the BPD
Main Group 1: Disinfectants and general biocides Product types: 1. Human hygiene products 2. Private and public health area disinfectants 3. Veterinary hygiene biocides 4. Food and feed area disinfectants 5. Drinking water disinfectants Main Group 2: Preservatives Product types: 6. In-can preservatives 7. Film preservatives 8. Wood preservatives 9. Fiber, leather, and polymerized materials preservatives 10. Masonry preservatives 11. Preservatives for liquid cooling systems and processing 12. Slimicides 13. Metal-working fluid preservatives
Main Group 3: Pest control Product types: 14. Rodenticides 15. Avicides 16. Molluscicides 17. Piscicides 18. Insecticides, acaricides and products to control other anthropods 19. Repellants and attractants Main Group 4: Other biocides Product types: 20. Preservatives for food or feedstocks 21. Antifouling products 22. Embalming and taxidermist fluids 23. Control of vertebrates
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The BPD interfaces with several other EU schemes for controlling various types of chemical product which can be grouped into four categories: product authorization schemes; general industrial chemicals legislation; classification and labeling Directives; and others such as worker protection and water Directives. Because of the wide variety of products defined in the BPD as biocides, careful delineation of certain products must be made to avoid making them subject to two authorization schemes. Biocidal products encompass medicines, veterinary medicines, cosmetics, and plant protection products. Where these products are already subject to EU authorization schemes, they are generally not intended to be subject to authorization under the BPD, but the borderline between the schemes needs to be carefully clarified. For example the interface between the BPD and the Plant Protection Products Directive [6] is clarified by the following examples: 1. Products applied directly or indirectly to crops in order to protect plants from organisms harmful to them are plant protection products, but those used as general hygiene disinfectants in empty structures, where it is not clear which products will be stored in the structure and the target organisms are not specifically plant pathogens, are biocidal products. 2. Algicides applied to soil or water to protect crops are plant protection products, whereas if intended to control on nonsoil surfaces (e.g. greenhouses), they are biocidal products. 3. Wood preservatives used up to the saw-mill stage to protect trees and felled timber are regulated as plant protection products; in the saw-mill and thereafter they are biocidal products (so called “saw-mill gates” principle). 4. Rodenticides used in the field to protect crops and plant products temporarily stored outside are plant protection products, but generally they qualify as biocidal products if used in buildings, including farm buildings. 5. When used to control plant pests, anthropod growth regulators are considered as plant protection products. However, pheromones and semiochemicals used in traps to monitor pest populations are outside the scope of both Directives, and only come under the BPD if the use is biocidal. Another area of dispute concerning scope is the regulation of in situ generated biocides. These include substances that are mixed together or otherwise generated by the consumer to create the biocidal active ingredient. The European Commission and member states have agreed that the in situ generation of ozone is not covered. The BPD applies only to biocidal products placed on the EU market, and since ozone is generated at the site of use, it is not regulated by the BPD.
3.2 The EU Biocidal Products Directive
3.2.3
Approval Systems
To obtain authorization for the marketing of a biocide, the applicant must submit two data packages: the first on the active substance, and the second on the formulated product. Also, the BPD makes a pragmatic but arbitrary distinction between those biocidal active substances on the market before 14 May 2000 (“existing” active substances) and those placed on the market for the first time after this date (“new” active substances). To gain authorization for a new active substance, the applicant should address all the data points for the active substance (given in Annex IIA, with some additional data points from Annex IIIA of the BPD) and at least one formulated product (Annex IIB, with additional data points from Annex IIIB). The member states and the Scientific Committee on Biocidal Products review the scientific content of the dossier and make an appropriate recommendation to the Commission. If the recommendation is favorable, the Commission will enter the active substance in an approved list (Annex I of the BPD). A review program is established in the BPD to assess systematically during a ten year period all the existing active substances. The data requirements are the same as for new active substances. Existing biocidal products can continue to be marketed while their active substances are reviewed under the ten year program. As with new biocides, once the data on the existing active substance have been evaluated and approved by the European Commission and the member states, the substance will be entered in Annex I of the Directive. A Technical Notes for Guidance (TNG) [7] covers the evaluation process and criteria for listing active substances in Annex I. The inclusion of an active substance in Annex I will be restricted to product use types listed in Annex V of the BPD (see Table 3.1) for which adequate data have been submitted. Annex I comprises three sections. Annex I itself lists regular active substances. Annex IA contains “low risk” active substances. Such Annex IA active substances cannot be carcinogenic, mutagenic, toxic for reproduction, sensitizing, or both bioaccumulative and not readily biodegradable. Annex IB contains “basic” active substances, the major use of which is not biocidal but which have a minor biocidal role. Substances entered in Annex I will initially be listed for up to ten years, and then be reviewed. The applicant can apply for ten year renewals as necessary. Somewhat controversially, under the principle of comparative assessment, the BPD (Article 10, para. 5) also gives the Commission the power to remove an active substance from Annex I if there is a comparable, alternative substance that presents “significantly less risk to health or to the environment”. Authorization of the formulated biocidal products is the responsibility of the individual member states. Full authorization under the BPD may only be granted if the active substance of the product is listed in Annex I.
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Standard biocidal products containing active substances in Annex I of the BPD require a full dossier of information (see Section 3.1.2 4), and applications for authorization are evaluated by the national competent authority without undue delay. Biocidal products containing only low risk active substances from Annex IA of the BPD can be registered with much reduced information, and the competent authority has to reach a decision on the registration application within 60 days. Biocidal products containing a new active substance for which a decision for Annex 1 listing is pending may be provisionally authorized for up to three years. New products containing existing active substances can be authorized under existing national schemes for up to ten years during the review program. The previous national schemes continue to apply to biocidal products containing existing active substances until the Commission makes a decision on whether to include that active substance into Annex I. If the listing in Annex I is not approved, the biocidal products containing them will be subject to a phase-out period. If the active substance is approved the existing biocidal product will have to be re-authorized by the member states. Under the BPD, applicants may use the concept of frame formulation to facilitate authorization of re-branded biocidal products. Frame formulations are groups of biocidal products with the same active substance of the same technical specification and use, which differ only in minor details of the formulation composition, such as the color and perfume ingredients, and hence have the same risk and efficacy. New biocidal products within a frame formulation can be authorized within 60 days. Once one Member State approves a biocidal product, all other member states must approve the product, subject to certain safeguards, according to the principle of mutual recognition. Thus a Member State receiving an application for approval of a biocidal product which has been already authorized or registered (if a low-risk biocidal product) in another Member State must authorize or register that product within 120 or 60 days respectively. The Member State can refuse the application only if the target species does not exist in that country, there is proven unacceptable resistance to the active substance, or if the circumstances (e.g. climate or breeding period) differ significantly from the lead country. The Standing Committee on Biocidal Products will resolve dispute between the member states. Member states may opt out of the mutual recognition procedure for avicide, piscicide and vermin-control biocidal products. 3.2.4
Data Requirements
Under the BPD [1], each biocidal product must have a dossier that contains information on its biocidal efficacy, physical and chemical properties, environmental effects and, where appropriate, any effects it has if brought into contact with food. The dossier should establish that the biocide is sufficiently effective without having unacceptable
3.2 The EU Biocidal Products Directive
effects on the target organisms or on the environment, including nontarget organisms. There must also be no adverse effects, direct or indirect, on human or animal health or groundwater from the residues of the substance. The BPD itself gives rules on data requirements (especially in Article 8). Annexes IIA and IIB specify detailed core data requirements common to all active substances and standard biocidal products, respectively. Note that much of the Annex IIB data are not needed for registration of a biocidal product containing only low-risk (Annex IA listed) active substances. In addition, specific additional data requirements apply for each of the 23 product types, and these are to be established on the basis of Annexes IIIA and IIIB, which contain indicative lists of tests for active substances and biocidal products, respectively. The specification of the additional data requirements takes into account the use characteristics of each biocidal product type. The common core data requirements in Annex II together with the specific data requirements in Annex III constitutes the complete set of data on which to base an adequate risk assessment. In principle, the data requirements are the same throughout the EU. They are intended, according to the BPD, to be the minimum necessary, but sufficient to conduct a proper risk assessment and make regulatory decisions. Due to the diverse exposure and potential risks associated with different biocidal products and the general nature of the rules given in the Directive, a Technical Notes for Guidance document (TNG) [8] gives detailed and practical guidance on which studies and other data are required when applying for authorization. This TNG also ensures efficient and harmonized day-to-day implementation of the Directive. However, expert judgement by the applicant and the competent authority is normally necessary in order to compile a satisfactory dossier. Member States and applicants negotiate the data requirements and identify, preferably at an early stage, any additional studies required. The Member State may request at any time additional information or studies necessary for the adequate assessment and decision making. The Member State may justify such additional studies either by the properties of the chemical (i.e. hazard) or by the predicted exposure. In addition to the core and specific data required, the applicant has to submit any additional available data, relevant to the risk assessment. The Member State also takes into consideration for the evaluation of the dossier any other relevant technical or scientific information available to them on the biocidal product, its components, metabolites, or residues. A high priority is to minimize the amount of animal testing. This means that all unnecessary testing of active substances and biocidal products must be avoided, and ideally existing data should be shared between applicants. In principle, studies should be compliant with the principles of Good Laboratory Practice (GLP) [9] and, conducted to the EU methods of Annex V [10] of the Dangerous Substances Directive or internationally recognized methods where appropriate (e.g. OECD guidelines [11]). New studies should be conducted to these methods. However, existing studies con-
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ducted to other methods may be adequate, and they have to be evaluated before conducting new tests, taking into account, amongst other factors, the need to minimize animal testing. To fulfil the data requirements without excessive costs, ways of reducing the amount of testing are very important, and there are several means to address a particular data requirement without testing. Information that is not necessary owing to the nature of the biocidal product or of its proposed uses need not be supplied. The same applies where it is not scientifically necessary or technically possible to supply the information. In such cases, the applicant must submit a justification acceptable to the competent authority. Such justifications for data waivers are evaluated on a case-by-case basis and, once there has been some experience in this area, the Commission will publish a compilation of cases in a Manual of Decisions. As a general rule, tests on an active substance should be carried out on the technical grade, including any essential additives (stabilizers etc) and impurities. However, certain specified physico-chemical testings are performed on a purified active substance. For the biocidal product approval, data may also be required on co-formulant substances if they are hazardous (i.e. substances of concern). Also, in certain cases, information on metabolites or environmental transformation products of the active substance may be needed. The information on active substances and biocidal products is summarized and interpreted in a standard format, according to Practicality Guidelines [12] for the preparation and presentation of complete dossiers for active substances and biocidal products and the subsequent competent authority reports. The guidance emphasizes how the dossier and reports should be prepared and structured, and covers the formatting of subdocuments and study summaries. The approach reduces the workload by harmonizing the format of the applicant’s summary dossier and the competent authority report derived from this, with the minimum number of subdocuments, and a clear demarcation between study summaries and the risk assessment. The structure of the dossier includes study summaries, summary tables, and completeness checks to make the assessment process easier. The standard formats have been designed in such a way that the competent authority can adapt the study summaries submitted by the applicant in an all-in-one approach without having to rewrite them for their evaluation report. The level of detail used in study summaries needs to be reasonably high, so that the competent authority can make an assessment without having to go back to the full report.
3.2 The EU Biocidal Products Directive
3.2.5
Risk Assessment and the Common Principles for the Evaluation of Dossiers
The Common Principles for the Evaluation of Dossiers are presented in Annex VI to the BPD, and give guidance on the approval of biocidal products. An important aspect of this is risk assessment both for the intended use and a reasonable worst-case situation. A further TNG detailing the risk assessment and decision-making processes for approval of biocidal products [13] supplements the framework of Annex VI. This is consistent with the Technical Guidance Document on risk assessment of existing and notified new chemical substances [14]. Risk assessment forms an important part of the regulatory process. The risk from a chemical substance is determined from its intrinsic hazardous properties and the likely exposures of humans and the environment throughout its life-cycle. The intrinsic chemical, health, and environmental hazardous properties can be quantified as a hazard assessment. The hazard of the biocide is assessed predominantly through toxicological testing in animal models. Under the BPD, these tests are prescribed in the Common Core Data set (Annex IIA for the active substance, Annex IIB for the biocidal product). Good quality human data may also be available, perhaps from epidemiological studies. The hazard assessment is combined with an exposure assessment to produce a risk assessment. If the outcome of the risk assessment is favorable, the substance will be recommended for Annex 1 listing. However, an unfavorable risk assessment may lead the assessor to ask for further information on toxicity or exposure in order to refine the risk assessment. If the risk assessment remains unfavorable a regulatory decision may be taken to implement risk management requirements, such as additional labeling or restrictions on use, to permit product approval. Exposure assessment is a more complex issue, because the biocidal product may be used in several of the 23 product types given in Table 3.1, and exposure from each type of application must be assessed. There are two basic options for exposure assessment, measuring (i.e. determining the exposure by direct measurement) or modeling. Modeling can be carried out using generic data for chemical release. Estimates of environmental release are improved by gathering information on the release of biocides from specific processes to develop EU biocide environmental emission scenarios (referred to as EUBEES). There is a corresponding project on emission scenarios and predictive models for human health. The risks from the proposed use of a biocidal product must be identified, and a decision made whether they are acceptable. Each active substance in the biocidal product requires assessment, as does any other substances of concern in the product. A substance of concern is a co-formulant that is classified as dangerous according to the Dangerous Substances Directive [4] (67/548/EEC) and present at above the concentration limits leading to classification (given in the Dangerous Preparations Direc-
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tive, 88/379/EEC, as amended, [5]). The results of these risk assessments on the component substances are integrated to give an overall assessment for the biocidal product itself, thereby determining the measures necessary to protect humans, animals and the environment during both the proposed use and in a realistic worst-case situation. The regulatory outcomes available to the assessor are as follows: the biocidal product cannot be authorized; it can be approved subject to specified restrictions and conditions; or that further information is needed to reach a decision. The decision-making process also takes into account the nature and severity of the adverse effects, the proposed risk management measures, and also the efficacy and potential benefits of the biocidal product. Biocidal products can only be approved if, when used as prescribed, they do not present unacceptable risks to man, animals, or the environment, are efficacious and use permitted active substances. Approval of biocidal products requires that they are used properly at an effective but minimized application rate. The regulatory authority also assesses the packaging, labeling, and accompanying safety data sheet. Risk characterization is also conducted regarding animals kept and used by humans. The humaneness of biocidal products targeted at vertebrates is also considered. The Danish and Finnish Competent Authorities evaluated full review dossiers on the active substances tebuconazole (as a wood preservative) and glutaraldehyde (as a paper slimicide and preservative for cooling-water systems) as pilot projects to validate the risk assessment procedures. All member states were involved, with workshops to facilitate discussion and learning. The hazardous properties of acute and repeat-dose toxicity, irritation and corrosivity, sensitization, mutagenicity, carcinogenicity, toxicity for reproduction and the physicochemical properties of each active substance or substance of concern in the biocidal product are identified and quantified, if possible, in terms of a dose-response effect. The repeat-dose and reproduction toxicity yields the no-observed-adverse-effect level (NOAEL), which is the highest dose level at which no adverse effects are realized. For acute toxicity, the LD50 value (or discriminating dose) partially quantifies the hazard. For irritation, corrosivity, skin and respiratory sensitization, mutagenicity, and carcinogenicity, the hazard is simply identified, in the absence of practical or theoretical means of evaluating a dose-response effect. The assessor estimates the exposure of professionals, nonprofessionals, and man exposed indirectly via the environment to each active substance or substance of concern in the biocidal product from use during its lifecycle. Exposure may be calculated using appropriate models, or estimated using measured data for existing or analogous products. Risk characterization involves comparison of the predicted exposure with the estimated effect level, qualitatively if necessary. Only as a last resort can the assessor take into account the use of personal protective equipment to enable a biocidal product to be used safely. Preferred measures include replacement of the hazardous
3.2 The EU Biocidal Products Directive
substance with a nonhazardous one, engineering solutions, such as local exhaust ventilation, and isolation techniques. Biocidal products containing category 1 or 2 carcinogens, mutagens or substances toxic to reproduction at above the classification limit for corresponding classification of the preparation (see Dangerous Preparations Directive, [5]) cannot be approved for use by the general public. The environmentally hazardous properties of the active substance and substances of concern are identified on the basis of test results or reasonable grounds for concern (i.e. bioaccumulation potential, persistence, shape of the ecotoxicity/time curve, indications of long-term adverse human health effects or structure-activity relationships, SAR). Full risk characterization is needed for each component if the biocidal product is classified as dangerous on the basis of that component, according to the Dangerous Preparations Directive (88/379/EEC, [5], as amended to include criteria for “dangerous for the environment”). The assessor evaluates the concentration-effect relationship to quantify the hazardous property in terms of a predicted-no-effect concentration (PNEC), or a qualitative estimation if appropriate. The PNEC can be derived from acute toxicity studies by dividing the LC50 in the most sensitive species by an assessment factor. With three acute studies (fish, Daphnia, and algae) the assessment factor is normally 1000. The assessment factor gives a margin of safety to account for inter- and intra-species variation and extrapolation to long-term exposures. If long-term toxicity studies are available, the PNEC is derived from the no-observed-effect level (the lowest dose in a particular test at which no effects are seen) in the most sensitive species by dividing by a lower assessment factor: perhaps 100 if two long-term studies are available, or 10 if there are three or more. The assessor estimates the predicted environmental concentration (PEC) for each environmental compartment (water, including sediment, soil, and air). Risk characterization entails calculating the PEC/PNEC ratio, or instead doing a qualitative evaluation, for each compartment, and then combining the results to find the overall conclusion. A biocidal product cannot be approved if one of the active substances, substances of concern, or a metabolite or breakdown product, is predicted to exceed the EU permitted concentration limits in ground water or surface water, which is intended for abstraction for drinking water. The user of the biocidal product must take measures to reduce accidental contamination of water. Products that contaminate soil and are expected to be persistent will not be approved, unless the applicant demonstrates that there is no unacceptable accumulation. Also, the applicant must address other unacceptable effects, such as the target species developing resistance to the biocidal product. The applicant must also substantiate the claimed efficacy of the biocidal product and in principle the product should be at least as efficacious as any existing products.
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3.3
The Review Program for Existing Biocide Active Substances and Biocidal Products
Existing active substances, i.e. those on the market before the implementation of the BPD on 14 May 2000, shall be reviewed at EU level for possible addition to Annex I (which currently is empty). The BPD (Article 16) contains the framework for this review program, and the Commission will carry out the review through a series of regulations. The European Chemicals Bureau (ECB) has produced a nonexhaustive indicative list of existing active substances [15]. Active substances on the final list and products containing them will benefit from the transitional arrangements of the BPD. Any substance not included on the final list of existing active substances will be considered as “new” and, together with biocidal products containing it, will have to meet the various provisions of the BPD before they can be marketed in the EU. Hence it is important for industry to ensure the final list is complete. The first Review Regulation [16] implements the first phase of the work program to evaluate existing active substances. This was not ready for 14 May 2000, but it was adopted as Commission Regulation (EC) Number 1896/2000 on 7 September 2000 and published in the Official Journal of the European Communities on 8 September 2000 and came into force 20 days later on 28 September 2000. Its purpose is to establish the definitive list of existing active substances, determine which of these will be supported through the full review procedure, begin the full review of the active substances for wood preservatives and rodenticides and provide a framework for phasing out unsupported active substances and the biocidal products containing them. A second Review Regulation, perhaps in force for mid 2003, will give the definitive list of existing active substances, and will list which have been notified, in accordance with the requirements of the first review regulation, as supported for subsequent full review. This second Review Regulation, and subsequent Regulations, will describe the priorities for the systematic review of the rest (other than rodenticides and wood preservatives) of the supported existing active substances. The deadlines for the full review dossiers for the second, third and final phases of the review may be mid 2006, mid 2007 and late 2008 respectively. There will be specific decisions on nonsupported active substances, detailing phase-out arrangements for them and biocidal products containing them. The first review regulation explains how manufacturers or formulators (or their solerepresentatives) can “identify” existing active substances for inclusion of the official list. Industry must submit the data given in Annex I of the first review regulation [16] by 28 March 2002, using the electronic form available from the ECB Website. Annex I data consist of commercial, technical and administrative data . The ECB will provide member states with a list of “identified” active substances (within an unspecified time). The member states are allowed three months to add further active substances
3.2 The EU Biocidal Products Directive
to the list, if they consider, for instance, that a particular unsupported active substance is important to their country. The Commission (again within an unspecified time) produces the definitive list of existing (identified) active substances, which is to be made public electronically. Active substances not on the list can no longer be used, but those on the list but not notified (see below) are allocated a reasonable phase-out period of up to three years. The first review regulation also establishes which of the existing active substances are to be supported for full review. Manufacturers, formulators, their sole-representatives, or associations do this by making a notification by supplying data given in Annex II to the regulation to the ECB, again by 28 March 2002. The information consists essentially of the Annex I identification data plus summaries of the physico-chemical, toxicological, and ecotoxicological studies corresponding approximately to the EU “Base Set” for notification of a new chemical substance (i.e. in Annex VIIA of the Seventh Amendment, [4]). Importantly, as part of the notification, the applicant (notifier) undertakes to complete the testing specified in Annexes IIA and IIIA of the BPD to support the active substance, either alone or as part of a task force, during the full review. IUCLID (version 3.2 or higher) which is modified for use with biocide active substances, has to be used to make the notification. A high proportion of European existing active substances will have inadequate data. Suppliers of active substances should gather available information (e.g. from existing studies and literature searching), and obtain expert regulatory advice in evaluating existing information, the use of surrogate data, conducting the outstanding studies, and preparing the dossier. Again member states have three months from receiving the list of notified active substances to notify other substances. The definitive list of existing active substances will specify by product types those active substances that have been notified. The notified existing active substances can continue to be marketed until they undergo full review (i.e. once all the necessary data in Annexes IIA and IIIA of the BPD are available), but only for the product types notified. Member states can indicate possible basic substances within six months, and anyone may notify a basic substance within 18 months of the first review regulation coming into force. Member states then have a further three months to notify further candidates. If the notification of the potential basic substance is accepted, the notifier is committed, unless exceptional circumstances apply, to submit all the information needed for full review and subsequent entry of the basic substance in Annex IB of the BPD. A draft of the first Review Regulation required industry to provide full data for review on an active substances in the first list within 18 months, which would have been impractical since some studies take up to four years. The final version, however, avoids this problem, yet still enables the full review program to begin, by dealing first with active substances that are likely already to have extensive test data from earlier national
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authorizations (the so-called twin-track approach). Hence applicants whose notifications are accepted for active substances of wood preservatives and rodenticides have to submit a full dossier to the designated rapporteur Member State by 28 March 2004. The Commission will use the notification data to decide the priority in which active substances will undergo full review, by product type. All successfully notified existing active substances will systematically be evaluated in full according to a timetable prescribed in subsequent review regulations. The time limit for the review of all existing active substances is ten years from transcription of the BPD in member states’ national law (i.e. by 14 May 2010). The applicant must have the rest of the BPD Annex IIA common core data, with any additional data from Annex IIIA which may be needed for an adequate assessment of the active substance. The applicant also has to include a dossier for at least one biocidal product containing the active substance. Once existing substances have been reviewed and approved at European level, all biocidal products containing them have to be registered (or re-registered) in each country of supply. The procedure for obtaining authorizations in multiple member states is facilitated by the mutual recognition agreement (Article 4 of the BPD). The UK Health and Safety Executive (HSE, the UK competent authority) has produced a Regulatory Impact Assessment, which was part of the drafting of the Biocidal Products Regulations to implement the BPD in the UK [17], in order to assess the commercial impact of BPD. They report that the UK Chemical Industry Association (CIA) estimate the cost of full testing for each active substance is between £ 2.1 million and £ 3.1 million, plus £ 0.16 million to £ 0.31 million for regulatory and administrative costs to compile dossiers, form task forces, etc. The industry is expected to support ca. 400 existing active substances during the review process. The HSE assumed that sufficient data are already available on 150 of these 400 active substances, because they are already registered under other schemes broadly equivalent to the BPD. For the remaining 250 active substances, assuming costs at the low end of the CIA ranges (i.e. £ 2.1 million plus £ 0.16 million), and also that for each of these active substances £ 0.78 million of data are already available (based upon the typical cost of registration in the USA), an overall cost of £ 1.48 million per active substance is derived, and a total cost of £ 370 million for the whole EU review program for active substances. Data will also have to be supplied for the first authorization or registration of each biocidal product. The HSE estimate that 800 products per year across the EU will require authorization or registration once their active substance has been reviewed and added to Annex I. However, it is estimated that for 200 of these sufficient information will already be available, because the products will have been registered under national approval schemes. The cost of providing data will vary substantially for different biocidal products. Some products will be very similar in formulation, and hence most of the information can be transferred between products, but for others substan-
3.4 European Union Chemical Control Measures
tial new testing will be needed. The HSE estimated the cost to industry would be between £ 10000 and £ 131000 to test each product, with an average of £ 78000. The biocides industry is structured differently to the agrochemical industry. Instead of each active substance being developed, and hence registered, by a single innovator company, many biocide active substances are likely to be supported by several producers, each with a partial set of safety studies. The sales value of biocides is much lower, so there are less resources available for review of existing biocides. The cost of conducting studies can constitute a considerable proportion of the development costs of a new biocide, so the periods during which these data are protected from unauthorized use by competitors is of key importance. A major problem for biocide companies in deciding whether to support their active substances in the EU review is the high degree of uncertainty in the cost of the studies needed. The experience gained in the various European national review program for biocides and pesticides, and indeed in the USA under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), can be brought to bear in operating the EU BPD. Many of the concerns expressed by industry during drafting of the BPD have been resolved, or will be addressed in the practical operation of the scheme, so that in general industry accept the BPD, in spite of the cost implications.
3.4
European Union Chemical Control Measures 3.4.1
Scope of European Union Legislation
There are 15 countries in the EU, or European Community (EC) as it is often referred to, and Austria, Finland, and Sweden are the most recent members. All the European Free Trade Association (EFTA) countries except Switzerland had entered into an agreement with the EU to form the European Economic Area (EEA). Only Iceland, Liechtenstein, and Norway are part of the EEA but not the EU. Although there were transitional arrangements and some differences are permitted, the 18 countries of the EEA constitute a single chemical market with essentially harmonized chemical safety measures and controls. Chemical control legislation in Switzerland is different to that of the EU. In practice products can normally be approved for Switzerland using the available EU information, or with only a little extra testing, although separate submissions to the Swiss regulatory authorities may be necessary. In due course chemical legislation in Switzerland will become more fully harmonized with the EU, but there does not seem to be any immediate likelihood of Switzerland joining the EU, or even the EEA, although the country is still part of EFTA.
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Finally, the relationship between Western Europe and the Central and Eastern European countries should be noted. Generally chemicals are not currently well regulated in these latter states, although some countries have compulsory certification or registration procedures. Many of these countries have applied for EU membership, however, and have entered into Association Agreements, which allow for existing chemical control measures to be harmonized with the EU.
3.4.2
European Union Chemicals Legislation
Many EU countries regulated biocides as general chemicals before the introduction of the BPD. Until the various facets of the BPD scheme come into operation, the previous national provisions continue in force. Hence it is useful to understand the EU controls for general chemicals. Chemical control in the European Union (EU) is based on a network of legislation for hazard communication and safety assessment. The framework is established by means of Council (or Council and Parliament) Directives or Regulations, with implementation by the Commission as Adaptations to Technical Progress or Commission Regulations, respectively, and associated guidance documents on working practices and administrative provisions. EU legislation is brought into force in individual member states by national laws, regulations and administrative procedures and hence, although chemical control is fundamentally harmonized, there can be minor differences between countries. All “dangerous” substances have to be classified, packaged, and labeled according to the requirements of the so-called Dangerous Substances Directive [3] (67/548/EEC), as amended [4]. Substances officially classified as dangerous are listed in Annex I of the Dangerous Substances Directive (67/548/EEC), which is updated by the Commission periodically by means of Adaptations to Technical Progress. The criteria to enable substances to be classified and labeled are given in Annex VI of this Directive [18]. Substances are classified for labeling by evaluation of their physical, toxicological, and ecotoxicological properties. There are 15 “dangerous” classifications: explosive, oxidizing, flammable, highly flammable, extremely flammable, harmful, toxic, very toxic, irritant, corrosive, sensitizing, carcinogenic, mutagenic, toxic for reproduction, and dangerous for the environment. Labeling consists of appropriate hazard symbols and information on potential hazards and safety precautions in the form of standard phrases (R- and S-phrases, respectively). The EU scheme for classification, packaging, and labeling of dangerous “preparations” (i.e., formulated products consisting of a mixture of substances) is specified in the Dangerous Preparations Directive [5] (88/379/EEC), which is updated from 30 July 2002 by Directive 1999/45/EC.
3.4 European Union Chemical Control Measures
Industrial users of dangerous chemical substances or preparations must be supplied with a safety data sheet (SDS), according to Commission Directive 93/112/EEC [19]. The classification, packaging, and labeling of biocidal products is the same as for chemicals, except that insecticide, acaricide, rodenticide, avicide, and molluscicide products are covered by the provisions of Council Directive 78/631/EEC [20]. Therefore, the active substance will generally be classified and labeled according to Annex VI [18] of the Dangerous Substances Directive (67/548/EEC) on the classification, packaging, and labeling of dangerous substances. The Dangerous Preparations Directive [5] also applies to biocidal products. Safety data sheets are also required for biocide active substances and products as for chemicals. New chemical substances must be notified according to the Seventh Amendment [4] (92/32/EEC) of the Dangerous Substances Directive before being placed on the EU market. The physico-chemical, toxicological, and ecotoxicological studies required depend on the supply level. Chemicals controlled under separate EU legislation, such as those for exclusive use in medicinal products, are exempt from notification, as are “existing” chemical substances, which are defined as those listed in the European Inventory of Existing Commercial Chemical Substances (EINECS) [21]. The Existing Chemicals Regulation [22] (793/93) on the evaluation and control of the risks of existing substances applies to all EU manufacturers or importers of existing chemical substances. The available data on substances supplied at above 1000 tonnes per annum has been reported and used for priority setting to select particular existing substances for thorough review with full “base-set” data (corresponding Annex VIIA of Directive 92/32/EEC, [4]). Commercial and technical data of substances supplied at above 10 tonnes per annum has also been reported. Risk assessment is conducted on notified new substances according to the general principles of Commission Directive 93/67/EEC [23]. Of the many reported existing chemicals, a priority-setting scheme is used to determine which require full risk assessment according to the general principles of Commission Regulation Number 1488/94 [24]. Risk assessment of new and priority existing chemicals involves hazard identification, hazard characterization by assessing the effect of dose (or concentration), or response (or effect) then comparison of this with an exposure assessment to produce a risk characterization covering both human health and environmental effects. These risk assessments are subsequently combined in an overall integration of conclusions. Assessors reach a conclusion after risk characterization of each of the identified hazardous properties, and those for which there are other reasonable grounds for concern, for each appropriate human population and environmental compartment. The risk assessment, after any necessary refinement, could include recommendations for risk reduction. The necessary risk reduction measures are adopted at EU level using existing provisions; for existing chemicals those measures already applied are
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taken into account. Recommendations may include modification of the classification, packaging, or labeling of the substance, the SDS, or the recommended emergency procedures. Alternatively, the relevant control authorities may be advised to consider controls for the protection of man and the environment by means of, for example, occupational exposure or environmental discharge limits. Very occasionally, restrictions on marketing and use under the Marketing and use Directive (Council Directive 76/769/EEC, as amended) [2] may be necessary, but only after a risk-benefit analysis. Note that under the BPD, in cases where active substances are evaluated and refused listing on Annex I, the Commission must bring forward proposals under the Marketing and Use Directive to restrict their use.
3.4.3
Other European Controls Affecting Biocides
Biocides, whether new products approved under the BPD, or existing products covered under the transitional arrangements by the previous national measures, are also subject to other control measures which affect them at all stages of their life cycle. Chemical control legislation, including the degree of its practical enforcement, varies between countries, as does the associated official advice and voluntary industry codes of practice. These systems for chemical control are being developed and improved, sometimes with a view to international harmonization. Chemicals have to be classified, packaged, and labeled according to the United Nations (UN) scheme for safe transport [25], i.e., by ship, inland waterways, air, rail, and road. Advice on emergency action to take following accidental spillage has to be available, e.g., from Transport and Emergency (TREM) cards, poison centers, or other information sources. Safe transport of marine pollutants is ensured by MARPOL 73/78 [26], which is in effect a supplement to the International Maritime Dangerous Goods Code of the International Maritime Organization. Discharge of pollutants to air and water are controlled by suitable means [27], to enforce the appropriate national environmental quality standards or internationally agreed pollution control targets, such as the release of ozone-depleting chemicals according to the Montreal Protocol [28]. The disposal of waste chemicals, including absorbed spillages and contaminated containers, is also regulated to ensure pollution is minimized [29], and recycling and the use of safer or less polluting chemicals is encouraged. Biocides have to be used safely in the workplace, in compliance with EU [30] and national worker safety legislation and any applicable occupational exposure limits or standards. Also, the necessary emergency measures to be taken following accidental spillage or poisoning have to be assessed, and national fire control legislation will also apply. Exceptional risks to the community surrounding a chemical plant may have to
3.5 National European Biocide Authorization Schemes
be evaluated under major accidents hazards legislation, such as the EU Seveso Directive [31]. Chemical products have to be fit for their intended purpose and may be covered by mandatory or advisory product standards. They will certainly be subject to civil legislation on product liability. Industry association voluntary codes of practice may apply, or alternatively a manufacturer may decide it is commercially undesirable to sell a product containing chemicals with certain properties (e.g., those that are positive in an Ames test for mutagenicity) even though there is no legal or ethical restriction. The choice of chemicals to use in the manufacturing process may be governed by the desire to have an environmental (ECO) label for the finished product, to obtain a competitive advantage in retail sales. Finally, the packaging of the finished product might be chosen with a consideration of packaging waste legislation, such as the EU Scheme [32] or national schemes (notably in Germany). Some countries, such as Finland, Norway, and Sweden, require chemicals to be reported to commercial product inventories. Furthermore, the appropriate national Customs requirements have to be fulfilled before chemicals can be imported. There may also be restrictions on the export of substances banned or restricted in the country of manufacture, because of the UN Prior Informed Consent program [33]. Some products may be used in such a way that they are regulated not only by general chemical or biocide legislation, but also as other chemical products, such as detergents [34], or offshore chemicals under the OSPAR harmonized offshore chemical notification scheme [35] of the Oslo and Paris Commissions.
3.5
National European Biocide Authorization Schemes 3.5.1
Introduction
Before the BPD, provisions for controlling biocidal products in individual EU member countries were very diverse, and in many cases there were no specific provisions. Where formal arrangements existed, they ranged from EU notification procedures under general chemical legislation described previously, to specific approval or registration schemes for certain categories of perceived higher risk biocides (e.g. wood preservatives). Regulation of such chemical products varied considerably between countries, and it was not uncommon for the same chemical to be defined as an industrial chemical in one country, as a biocide in another, and to be covered by both categories in a third. The more strictly controlled biocides tended to be those used for wood preservation, vertebrate and invertebrate pest control, and as disinfectants espe-
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cially in food or animal feed areas. However, such approval schemes invariably fell short of the rigorous registration required for plant protection products, and there were marked inconsistencies in regulatory procedures and data requirements between countries. Until existing active substances are reviewed, and the biocidal products containing them registered under the BPD, the previous national authorization measures continue to apply. It is even possible to have new biocidal products containing an existing active substance approved under these existing arrangements. Hence some of the most important European national biocide authorization schemes are described briefly. More detailed summaries of national regulations for biocides worldwide, including EU countries, are to be found in an OECD survey [36]. The BPD was based on these national schemes, and the practical aspects for its implementation developed within the culture of these existing systems. Regulators, industry, and politicians responsible for developing the BPD were clearly influenced by what had gone before.
3.5.2
The Netherlands
The primary legislation controlling the authorization, sale, and use of pesticides (including biocides) in the Netherlands is the Pesticide Act of 1962 [37], which stipulates the registration procedure that allows a pesticide to be sold, stored, or used. The Act has been implemented through Regulations [38] covering: limitation of use to specified applications or user categories; professional training and licensing, with environmental requirements such as controls on the distance of fumigated object from surrounding buildings; publicity and advertising; waste disposal of pesticides and containers; surveillance; and residues in foodstuffs. The same basic regulatory principles apply as for plant protection products. Trade and use of these pesticide products is permitted only after authorization. The applicant provides a full dossier that includes physical and chemical information, efficacy, toxicology, residues, and environmental data. Data requirements are specified for each product category. From these data the efficacy is judged by the Competent Authority, as well as the risks for public health, operators, and the environment. The Dutch regulations for biocidal products encompass a very broad range of products, including disinfectants, pesticides for domestic and industrial use, wood preservatives, antifouling paints, fumigants for stored products, ectoparasiticides, and human-skin insect repellants. All herbicides, however, are considered as plant protection products. In principle all 23 product types of the BPD are covered, except for products used on animals. According to the Dutch Pesticide Act, a biocidal product is any substance or preparation containing one or more active substances intended for use in the following:
3.5 National European Biocide Authorization Schemes *
*
*
*
controlling or repelling organisms which may cause injury to plant products or to designated animal products; controlling or repelling animal or plant organisms in or on: – buildings and other premises, not used to house animals or as nurseries for plants; – water-supply services, swimming baths, and waters used for bathing and swimming as well as camping sites, caravans and tents; – refuse dumps; – vehicles, ships, and aircraft, not used for the transport of animals; – materials, apparatus, and utensils; controlling or repelling animals, which may cause diseases in or transmit diseases to man, (except products separately regulated as medicinals); controlling or repelling animals, other than those referred to under the above point, for the prevention of nuisance to man.
Before authorization is granted, the product must be established as: * *
*
sufficiently active; producing no harmful side effects when used as prescribed, including: – harming plants or plant products; – endangering humans, directly or indirectly; – harming animals, directly or indirectly; – endangering the person applying the product; – endangering those coming into contact with residues of the product; – harming the quality of foodstuffs; – unnecessarily damaging vertebrates to be controlled; – harming the quality of ground water; – harming the environment, considering the product’s distribution in soil and water and effect on nontarget species. complying with the requirements for classification, packaging, and labeling.
The information needed for approval is specified in the Dutch Regulations, which distinguish between plant protection products and biocides. The biocides are given a Classification Group according to the use-category, which determines which data are required. For example, industrial biocides for use in cooling water and in liquids during production processes in the paper industry are in Classification Group D5. Wood preservatives applied outdoors, or for wood to be used outdoors, are in Classification Group C1; those applied indoors, or for use indoors, are in Classification Group C2. The applicant should submit all data unless: * *
public data are concerned (e.g. published material); the data have previously been submitted to the Dutch competent authority by some-
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*
*
*
one else who has given written permission to use them in the current application; the data have been submitted to the Dutch competent authority in support of another application, and the authorization is more than ten years old; the data have been submitted by someone else in support of an application for extension or amendment of a registration, and five years have passed since the extension or amendment was granted; the data have been submitted before 5 February 1994 by someone else in support of an application for registration, or extension or amendment or a registration.
The information on a biocidal product is summarized in Application Form A, which contains the following sections: Section A, data concerning the applicant; Section B, information on the product; Section C, composition of the product; Section D, information on the active ingredient; Section E, information on the toxicity of the formulated product and the active products and its metabolites; Section F, information on the metabolism in the plant, and on residues; Section G, behavior of the product and its metabolites in soil, water, and air; and Section H, toxicity to organisms present in the environment. In many cases, the guidelines recommend relevant international or national test guidelines as the appropriate test methods, especially for Sections C, D, E, and H, such as OECD [11], or EU Annex V [10] guidelines. The Dutch competent authority is the Board for the Authorization of Pesticides (College voor de Toelating van Bestrijdingsmiddelen, CTB). Fees are payable to the CTB. Anyone intending to conduct or commission animal testing is obligated to ask the CTB whether the studies have previously been submitted. The enquiry is made on a form available from the CTB, which establishes the bone fide intention of the applicant. The CTB will divulge whether the product has been registered and the identity of those holding the data. The application procedure in principle follows a defined timetable. Within two weeks of receipt of the form, the CTB issues an application number. The application is checked for completeness, including all the appendices and declarations, and within twelve weeks the applicant is informed of any deficiencies. Thirty-four weeks after the CTB have declared the application to be complete and have received the fees for summarizing and evaluation, they inform the applicant of additional data requirements. Within 48 weeks after either receipt of the fees or any additional data requested, the CTB will make a decision on the application based on efficacy and safety. An authorization is valid until a specified expiry date, up to a maximum of ten years, and can be extended by the holder upon application, and after it has been demonstrated that the criteria for authorization are still being met.
3.5 National European Biocide Authorization Schemes
3.5.3
Belgium
The royal decree of 5 June 1975 [39] concerning conservation, trade, and the utilization of pesticides and for nonagricultural use covers nearly all groups of biocidal products. The decree regulates an extensive range of product use: antimicrobials used in buildings, transport, waste sites, swimming baths; preservatives to prevent decay or damage to animal or plant products; insecticides to combat or eliminate ectoparasites of small domestic animals; and disinfectants used to treat plants, water, or soil used to prevent illnesses to man or to animals. Notable exemptions include substances and preparations used as antiseptics or disinfectants for surgical material, additives for food and feeding stuffs, and biocidal products used for research and scientific trials. The detailed requirements are contained in a comprehensive explanatory document “La Mise sur le Marche d’un Pesticide a Usage Non-Agricole”, issued by the Conseil Superieur d’Hygiene in November 1995 [40]. This document explains the need for either a full dossier (especially mammalian toxicology), or a reduced dossier if the active ingredient is already registered in Belgium, including for other uses such as in a plant protection product. The appraisal procedure and timing is as follows. The applicant provides a dossier and fees to the Ministry of Public Health. The Ministry checks the administrative aspects of the dossier within a deadline of 14 days, and then send copies to the Scientific Secretariat to evaluate the completeness of the dossier, within a deadline of one month. The Scientific Secretariat will contact a company directly if more information is needed, and any additional data are sent directly to the Scientific Secretariat. When a dossier is judged to be complete, it is then evaluated by the Human Health Council, who are expected to give a verdict within four months. If more information is needed, the Human Health Council requests the information through the Administration Department of the Ministry of Public Health, who approaches the applicant.
3.5.4
The United Kingdom
Prior to 1985, pesticides were controlled in the UK by the nonstatutory Pesticides Safety Precaution Scheme, which was formally agreed between the British government and the agrochemical industry. This scheme was not directly concerned with the efficacy of pesticides, but a separate arrangement, the Agricultural Chemicals Approval Scheme, covered this for products used in agriculture, horticulture, forestry, home gardens, and for control of insect and mite pests on farm-stored grain. The Control of Pesticides Regulations (COPR) [41] which were established under Part III of the Food and Environment Protection Act 1985, came into force
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on 6 October 1986. The Pesticide Safety Precautionary Scheme and the Agricultural Chemicals Approval Scheme effectively lapsed on this date, but statutory approvals were granted to all products that had at least provisional clearance under these nonstatutory arrangements. The COPR define in detail those types of pesticides which are subject to control, prescribe the approvals required before any pesticide may be sold, stored, supplied, used, or advertised, and allow for general requirements on use, including aerial application. They apply with certain exemptions to pesticides and to any substance, preparation, or organism prepared or used for any of the following purposes: (a) protecting plants or wood or other plant products from harmful organisms; (b) regulating the growth of plants; (c) giving protection against harmful creatures; (d) rendering such creatures harmless; (e) controlling organisms with harmful or unwanted effects on water systems (including sewage works), buildings or other structures, or on manufactured products; and (f) protecting animals against ectoparasites. The applicant submits the dossier for the nonagricultural pesticide to the HSE. The Interdepartmental Secretariat (IDS) considers more complex applications, which are to be evaluated by the Committee Procedure. This procedure is used if the active ingredient in the new product has not been considered for approval previously, for pesticides with novel means of application, or other proposals that appear to offer a new hazard. The IDS is part of the Advisory Committee on Pesticides (ACP), which is an independent body whose function is to advise government ministers on the level of approval that should be granted. For the registration of nonagricultural pesticides that contain recognized active ingredients there are three routes of approval: *
*
*
Secretariat. This type of application applies when precedents already exist for the type of product required, i.e. where the active ingredient levels are below the maximum approved for the areas of use, application method, and user group. Approval takes up to 90 days. Departmental. This type of application applies when the product is without precedent in the area of use, the amount of active ingredient, or formulation type. The application requires a risk assessment, based on all previous data, which is evaluated by the IAS. The approval takes 6 to 12 months, and there is no guarantee of success. Committee. This application is required when the use pattern of the product is radically changed, for example from professional to amateur use. The applicant must submit information on efficacy, and mammalian and environmental toxicology. The IPS and the ACP evaluate the data. The application takes typically 18 months to three years to complete, again with no guarantee of success.
3.5 National European Biocide Authorization Schemes
There are three levels of approval: experimental permit for research and development purposes on the applicants own premises; provisional approval, once the HSE is satisfied that the product may be safely used; and full approval when all data requirements have been fulfilled. The data required for approval consists of a core set for all biocidal products, with additional data required according to the type of product and its area of use. For general biocides, applicants are referred to the Non-Agricultural Pesticides Registration Handbook [42]. The ACP and IDS have data requirements for active substances and their products for each end-use covered by COPR, and, although some of the data requirements are specific to the particular end use, the basic core data are common to all areas. All testing should be performed on representative batches of the active substance or formulation in accordance with internationally acceptable guidelines (preferably EU Annex V Methods [10] or OECD guidelines [11]) and, where appropriate, to GLP [9]. The data requirements also depend on the label claim, areas of use, and methods of application, and user category. The user-categories for nonagricultural pesticide are: (a) industrial, with the product only used in a factory situation (currently applied only to wood preservatives); (b) professional, with the product applied by trained or experienced operators; and (c) amateur, with the product available to the general public. Where use of the product may result in significant operator, consumer or environmental exposure to the substance, additional data will be required. Also, some of the additional data may be required if the core-package data is inadequate for risk assessment. Data for active substances and product-related data submitted in support of applications for the first commercial approval are protected for ten years. Active substance data subsequently required to support continued approval, or for review of the pesticide, are protected for five years. All active substances are subject to a full scientific review regarding safety ten years from the date of the first commercial approval of the products containing them. The review involves evaluating the safety of all products containing the substance. Reviews are then to be repeated at ten year intervals, although an emergency review can be undertaken if concerns are expressed about a pesticide. Hence the HSE have comprehensive data packages on certain active ingredients. Companies wishing to use these active ingredients may buy from a “recognized source”, who will supply the HSE with a letter of authorization allowing access to the data with regards to the application for the formulated product.
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3.5.5
Scandinavia Denmark The current approval system for pesticides [43] was set up in Denmark with the entry into force of the Chemical Act in 1980. The approval system is applicable to both plant protection products and biocidal products. Approval by the Danish National Agency of Environmental Protection (EPA) is subject to proof by the applicant that the product is not considered dangerous to health or to the environment. With the amendment of the Chemical Act in 1987, stricter provisions were made for hazard assessment of pesticides. The EPA have designated a framework for the assessment of pesticides. The Chemicals Act was amended in 2000 in order to implement the BPD. In the transitional period, before the EU BPD scheme comes fully into force, the biocidal products regulated under the current Danish scheme are products to control fungus attacking wood, algae, slimicides for pulp, vermin on domestic animals, pests in textiles, pests in timber and woodwork, insects, snails, mites and products to control rabbits, water voles, mice, and rats. Also, registration is needed for chemical repellant products to control the above mammals and lower animals. 3.5.5.1
3.5.5.2 Finland
In Finland, wood preservatives and slimicides are “protective chemicals” which must not be manufactured, imported, delivered for sale, or used without advance approval according to the Chemicals Act 744/1989 as amended [44], the Decree on Wood Preservatives and Slimicides (123/1994) [45] and the Decision (256/1994) of the Ministry of the Environment [46]. Applications are made to the Finnish Environmental Institute (FEI). Prior approval is not needed for reported protective chemicals or products for wood-preserving paints, and instead these are notified to the FEI. The Amended Chemicals Acts 1198/2000 [44] requires registration of antifouling products. Finally, premarketing approval is needed for rodenticides, molluscicides, insecticides, and repellents under the Pesticides Act (327/69) [47] from the Pesticide Board of the Plant Protection Center. Standard EU [10] or OECD [11] GLP-compliant [9] studies are required.
3.5.5.3 Sweden
Miljo¨balken 1998:808 (Chapter 8) in the Swedish Environmental Code [48] makes general provisions for testing and authorization of plant protection products and a number of biocidal product types. Ordinance SFS2000:338 [49] covers biocidal products. The term “pesticide” in the Ordinance is taken to mean a chemical product
3.6 Conclusion
that is intended for use to protect against damage to property, sanitary nuisances or other comparable nuisances caused by plants, animals, or microorganisms. Authorization is normally for five years, but in some cases can be for ten years. The Swedish National Chemicals Inspectorate (referred to as KEMI) is the competent authority. Note that KEMI also practice comparative assessment, so that inclusion on the national approved list may be refused, or existing approvals may be withdrawn, if another chemical is considered safer (considering health, environmental, efficacy, and practical and economic aspects), or if nonchemical substitutes are available.
3.6
Conclusion
The EU is one of the three main biocide markets, together with the USA and Japan. Until the BPD came into force, the European market was fragmented, with different regulatory requirements in different EU Member States. Some countries, notably Germany, had no specific control measures, and biocides were covered by the general EU chemicals legislation. Others, such as the Netherlands, had their own vigorous national approval schemes, requiring extensive testing. Hence the level of protection of humans and the environment from the possible adverse effects of biocidal products varied across Europe. The disharmony in regulatory obligations also resulted in nontariff barriers to trade in biocidal products within the EU. The BPD rectified both these problems, by introducing a harmonized scheme for appraisal of biocidal products within EU countries, using active substances evaluated at EU levels, to ensure a high level of safety for humans and the environment. The BPD is the legal framework for the new EU Scheme for authorization of biocidal products and evaluation of active substances. It took many years to finalize, with extensive debate with stakeholders and a great deal of political compromise from the EU and national law-making bodies involved in the complex EU legislative development process. The BPD is clearly influenced by previous EU schemes, especially for general chemicals and plant protection products, and the various national approval schemes for biocidal products. The practical implementation of the scheme is left to the European Commission, the ECB and the national competent authorities. The diverse background, experience, and interest of these diverse parties has meant further compromise in developing the practical aspects for operating the BPD. Industry, academics, the public, and environmental pressure groups have also had input into the technical guidance documents which are pivotal to the smooth operation of the scheme. Many of the early concerns of industry with the BPD seem to have been resolved, for example regarding comparative risk assessment.
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For worldwide marketing of a biocidal product, the regulatory hurdle used to be the US FIFRA. Now, generally, the cost of testing for the EU BPD is higher, and the time to get EU approval is likely to be at least as long as for the USA. The biocides industry may not be able to support such extensive testing, especially for certain less profitable markets. Hence development of new products may be adversely affected. The problem may be especially acute for existing biocide active substances, because in principle the same amount of data are needed for the ongoing 10-year EU review program, it is virtually certain there will be far fewer biocidal products on the market, with a reduced selection of active substances.
References [1] Directive of the European Parliament and Council of 16-2-98 concerning the placing of biocidal products on the market (98/8/EC), Off. J. Eur. Communities, L123, 24-04-98. [2] EC Council Directive 76/769/EEC of 29-4-75 relating to restrictions on the marketing and use of certain dangerous substances and preparations (76/769/EEC), Off. J. Eur. Communities, L262, 27-9-76, as amended. [3] Council Directive 67/548/EEC, as amended and adopted to technical progress, as partly published up to January 1997 as “Classification, packaging, and labeling of dangerous substances in the European Union”, European Commission, Luxembourg, 1997. [4] EC Council Directive of 30-4-92 amending for the seventh time Directive 67/548/EEC on the approximation of the laws regulations and administrative provisions relating to the classification, packaging, and labeling of dangerous substances (92/32/EEC), Off. J. Eur. Communities, L154, 05-06-92. [5] EC Council Directive of 31-5-99 amending the Directive 88/379/EEC on the approximation of the laws, regulations, and administrative provisions of the member states relating to the classification, packaging, and labeling of dangerous preparations (99/45/EC), Off. J. Eur. Communities, L200, 30-07-99. [6] EC Council Directive of 15-7-91 concerning the placing of plant protection products on the market (91/414/EEC), Off. J. Eur. Communities, L230, 19-08-91, as amended. [7] Technical Notes for Guidance on the inclusion of active substances in Annexes I, IA, and IB of the Biocidal Products Direc-
References
[8]
[9]
[10]
[11] [12]
[13]
tive, European Commission document, in preparation. Technical Notes for Guidance on data requirements, European Commission document, in preparation. Council Directive 87/18/EEC of 18-12-86 on the harmonization of the laws, regulations, and administrative provisions relating to the application of the principles of GLP and the verification of their application for tests on chemical substances, Off. J. Eur. Communities, L15, 17-1-87, as adapted to technical progress by Commission Directive 1999/11/EC of 8-3-99, Off. J. Eur. Communities, L77, 23-3-99. Annex V of Council Directive 67/548/EEC, as adopted to technical progress by Commission Directive 92/69/EEC of 31-7-92, Off. J. Eur. Communities, L383A,. 29-12-92, Commission Directive 96/54/EC of 30-70-96, Off. J. Eur. Communities, L24I, 30-9-96, Commission Directive 98/73/EC of 18-9-98, Off. J. Eur. Communities, L305, 16-11-98, Commission Directive 2000/32/EC of 19-5-00, Off. J. Eur. Communities, L136, 8-6-00 and Commission Directive 2000/33/EC of 25-4-00, Off. J. Eur. Communities, L136, 8-6-00. OECD Guidelines for the Testing of Chemicals, OECD, Paris, 1993, as updated. Guidelines for the Practical Implementation of Directive 98/8/EC, European Commission document, in preparation. Technical Notes for Guidance in support of Annex VI of the Directive, European Commission document, in preparation.
References [14] Technical Guidance Documents in support of the EC Commission Directive on risk assessment for new notified substances (93/67/EEC) and the Commission Regulation on risk assessment for existing substances ((EC)1488/94), European Commission document, April 1996. [15] Biocidal Products Directive: The Provisional List of Existing Active Substances (98/8/EC), http://ecb.ei.jrc.it/biocides. [16] EC Commission Regulation of 7-9-00 on the first phase of the program referred to in Article 16(2) of Directive 98/8/EC of the European Parliament and of the Council on biocidal products (No. 1896/2000), Off. J. Eur. Communities, L228, 8-9-00. [17] Proposals for the Biocidal Product Regulations (BPR) and approved Code of Practice on test methods for data submitted under the BPR. Consultative Documents 1999, CD149 C40 7/99, HSE books, Sudbury, UK. [18] Annex VI of Council Directive 67/548/ EEC, as adapted to technical progress by Commission Directive 93/21/EEC of 27-4-93, Off. J. Eur. Communities, L110, 4-5-93, Commission Directive 96/54/EC of 30-7-96, Off. J. Eur. Communities, L248, 30-9-96, Commission Directive 97/69/EC of 5-12-97, Off. J. Eur. Communities, L343, 13-12-97, Commission Directive 98/98/EC of 15-12-98, Off. J. Eur. Communities, L355, 30-12-98, as corrected by Commission Decision 2000/368/EC of 19-5-00, Off. J. Eur. Communities, L136, 8-6-00, and Commission Directive 2000/32/EC of 195-00, Off. J. Eur. Communities, L136, 8-6-00. [19] EC Commission Directive of 10-12-93 on Safety Data Sheets (93/112/EC), Off. J. Eur. Communities, L314, 16-12-93. [20] EC Council Directive of 26-6-78 on the approximation of the laws of the member states relating to the classification, packaging, and labeling of dangerous preparations (pesticides) (78/631/EEC), Off. J. Eur. Communities, L206, 29-7-78. [21] Notice No 90/C 146 A/01 Commission communication pursuant to Article 13 of Council Directive of 27 June 1967 on the approximation of the laws, regulations, and administrative provisions relating to the classification, packaging, and labeling of dangerous substances, as amended
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29] [30]
[31]
by Directive 79/831/EEC–Einecs (European Inventory of Existing Commercial Chemical Substances) (67/548/EEC), Off. J. Eur. Communities, C146, A.15-6-90. Vol. 33. EC Council Regulation No. 793/93 of 23-3-93 on the evaluation and control of risks of existing substances (793/93/EEC), Off. J. Eur. Communities, L84, 5-4-93. Commission Directive 93/67/EEC of 20-7-93 laying down the principles for the assessment of risks to man and the environment of substances notified in accordance with Council Directive 67/548/EEC, Off. J. Eur. Communities, L227, 8-9-93. Commission Regulations (EC) No. 1488/ 94 of 28-6-94 laying down the principles for the assessment of risks to man and the environment of existing substances in accordance with Council Regulation (EEC) No. 793/93, Off. J. Eur. Communities, L161, 29-6-94. United Nations Recommendations on the Transport of Dangerous Goods Model Regulations, Eleventh revised edition, United Nations, New York and Geneva, 2000. International Convention for the Prevention of Pollution from Ships adopted 1973, modified by Protocol of 1978 (MARPOL 73/78). Chapters 4 and 6 of “Manual of Environmental Policy: the EU and Britain”, ed. N. Haigh, Elsevier Science, Oxford, 2000. Council Regulation (EC) No. 3093/94 of 15-12-94 on substances that deplete the ozone layer, Off. J. Eur. Communities, L333, 22-12-94, as amended. Chapter 5 of ref [27]. Council Directive 89/391/EEC of 12-6-89 on the introduction of measures to encourage improvements in the safety and health of workers at work, Off. J. Eur. Communities, L183, 29-6-89, and the individual Directives and their amendments within the meaning of Article 16(1) of Directive 89/391/EEC. EC Council Directive of 26 January 1994 on the control of major accident hazards involving dangerous substances (92/82/EC), Off. J. Eur. Communities, L10, 14-1-97.
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3 Regulatory Control of Biocides in Europe [32] EC Council Directive of 9-9-93 on packaging and packaging waste (94/62/EC), Off. J. Eur. Communities, L365, 31-12-94. [33] Decision 18/12; Development of an international legally binding instrument for the application of the prior informed consent procedure for certain hazardous chemicals in international trade, and consideration of further measures to reduce the risks from hazardous chemicals. Adopted 18th Session of Governing Council of United Nations Environment Program, Nairobi, 15 – 26 May 1995. [34] EC Council Directive of 16-6-71 on detergents (73/404/EEC), Off. J. Eur. Communities, L347, 17-12-73, as amended. [35] a) Offshore Chemical Notification scheme: PARCOM Decision 96/3 on a harmonized mandatory control system for the use and reduction of the discharge of off-shore chemicals; b) Harmonized Mandatory Control System for the Use and Reduction of the Discharge of Offshore Chemicals: OSPAR Decision 2000/2. [36] OECD Series on Pesticides, Number 9; Report of the Survey of OECD Member Countries’ Approaches to the Regulation of Biocides, ENV/JM/MONO(99)11 28 April 1999, http://www.oecd.org/ehs). [37] Bestrijdingsmiddelenwet, 1962. [38] Regeling Toelating bestrijdingsmiddlelen, 5 February 1994. [39] Arrt royal du 5 June 1975 relatif la conservation, au commerce et l’utilisation des pesticides et des produits phytopharmaceutiques, moniteur belge, 4.11.1975 p.13864 (as amended). [40] La Mise sur le marche d’un pesticide a usage non-agricole Project, Conseil Superieur d’hygiene, November 1995.
[41] Control of Pesticide Regulations (COPR) 1986, as amended, Statutory Instrument Number 1510. [42] The Non-Agricultural Pesticides Registration Handbook, HSE, latest version. [43] Statutory order from the Ministry of the Environment Act, No. 212 of 23-5-79 on chemical substances and products, as amended by Act No. 68 of 20-2-80, by Act No. 285 of 13-5-87, and by Act No. 791 of 10-12-87 on Chemical pesticides, the Consolidated Act from Ministry of Environment and Energy No 21 of 16-1-96 on Chemical substances as amended by Act No 256 of 12 April 2000, and products and the Statutory Orders from The Ministry of Environment and Energy No 722 of September 1997, No 241 of April 1998 and No 313 of 5 May 2000. [44] The Finnish Chemicals Act 744/1989, as amended by 1198/2000. [45] Decree on Wood Preservatives and Slimicides (123/1994) (Chemical preservatives). N:o 123 Suojauskemikaaliasetus, Annettu Helsingissa II pa¨iva¨na¨ helmikuuta 1994, p.335. [46] Decision 256/94, Ministry of the Environment, 1-5-94, No. 256 Ympa¨risto¨ministerio¨n pa¨a¨to¨s, suojauskemikaalien ennakkohyva¨ksymis – ja ilmoitusmenettelysta¨. Annettu Helsingissa 5 pa¨iva¨na¨ huhti kuuta 1994. [47] The Finnish Pesticides Act 327/69. [48] Chapter 14 of Miljo¨bakan 1988:808 in “The Swedish Environmental Code”, Fritzes Offentliga, latest version. [49] Swedish Ordinance SFS 2000:338.
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4
Regulation of Biocides in the United States Sue Crescenzi
4.1
Introduction to Pesticide Regulation in the United States 4.1.1
Legal Authority
In the United States, there are two different statutes that provide the basis for the regulation of all pesticides including biocides and agricultural (plant protection) products: the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)[1] and the Federal Food, Drug, and Cosmetic Act (FFDCA) [2]. FIFRA is the principal statute regulating pesticides. It focuses on the safety of products and their labeling. FIFRA authorizes the US Environmental Protection Agency (EPA) to register (license) a pesticide prior to marketing [3]; to regulate the labeling of all pesticide products, including technical active ingredients and formulated end-use products [4]; to re-evaluate (re-register) pesticides registered prior to 1984[5]; to evaluate pesticides every 15 years [6]; to regulate all aspects of the sale, distribution and use of pesticides [7]; to impose post-registration obligations, including various reporting requirements [8] and the generation of additional data to support continued registration [9]; and to regulate pesticide exports and imports [10]. FFDCA sets forth the requirements for the establishment of legal pesticide limits (residues) for pesticides used in or on food or feed crops [11]. FFDCA also provides the basis for the regulation of pesticides with uses that may result in contact of the pesticide with food (food additive and food-contact substances) [12]. FFDCA is administered in part by EPA, and in part, by the Food and Drug Administration (FDA). FIFRA was first enacted in 1947 and has been amended on a number of occasions. The two most recent amendments are the Food Quality Protection Act (FQPA) of 1996 [13] and the Antimicrobial Reform Technical Corrections Act (ARTCA) of 1998 [14]. The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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4 Regulation of Biocides in the United States
FQPA, discussed in Section 4.5.2, has revolutionized the manner in which EPA assesses potential risks associated with pesticide residues which may be present on food. FQPA also has impacted the manner in which food-contact biocides in the United States are assessed and regulated. FQPA and ARTCA also have altered the jurisdiction for food-contact antimicrobial pesticides in the United States and is discussed more fully in Section 4.4.4.
4.1.2
Federal Agencies with Responsibility for the Regulation of Biocides
EPA’s Office of Pesticide Programs (OPP) administers FIFRA and also administers the FFDCA requirements for pesticide residues in food. FDA regulates the use of pesticides, primarily antimicrobials, as food additives* or food-contact substances**. Both are handled by FDA’s Center for Food Safety and Applied Nutrition (CFSAN), Office of Food Additive Safety. FDA regulated all chemical substances used as food additives or food-contact substances. However, when used to mitigate, kill or otherwise act against pests***, these compounds also are regulated by EPA as pesticides. Antimicrobial registrations are handled primarily by the Antimicrobial Division within OPP. OPP’s Registration Division generally handles registrations and responsibilities for “conventional” chemical pesticides. Details on antimicrobial and conventional pesticide registrations and other regulatory procedures are discussed in more detail in the following sections. (There is a separate OPP division for “biopesticide” products, which are not addressed in this discussion.) “Re-registration” actions are handled by the OPP Special Review and Reregistration Division (SRRD) and are discussed in more detail in Section 4.5.
*
A „food additive“ is defined as „any substance, the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food....“ FFDCA § 201(s); 21 U.S.C. 321(s). See Section 4.4.2 for additional information on the FDA regulation of food additives. ** A „food-contact substance“ is defined as „any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have any technical effect in such food.“ FFDCA § 409(h)(6); 21 U.S.C. 348(h)(6). See Section 4.4.3 for additional information on the regulation of foodcontact substances by FDA.
*** A „pest“ is defined as „(1) any insect, rodent, nematode, fungus, weed, or (2) any other form of terrestrial or aquatic plant or animal life or virus, bacteria, or other micro-organism (except viruses, bacteria, or other micro-organisms on or in living man or other living animals)“. FIFRA § 2(t); 7 U.S.C. 136(t). EPA’s regulations further qualify the term „pest“ as excluding any „fungus, bacterium, virus or other microorganisms ... on or in processed food or processed animal feed, beverages, drugs (as defined in FFDCA sec. 201(g)(1)) and cosmetics (as defined in FFDCA sec. 201(i)).“ A „pesticide“ is defined, in part, as „any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest ...“. FIFRA § 2(u); 7 U.S.C. 136(u).
4.2 Regulation of Biocides in the United States
4.1.3
Information Resources
EPA has promulgated a series of regulations on pesticide regulatory procedures and requirements, found at 40 Code of Federal Regulations (C.F.R.) Parts 150 through 186. EPA also has developed numerous guidance materials, much of which can be accessed through the OPP Internet Home Page, www.epa.gov/pesticides/. FDA regulations governing food additives are published at 21 C.F.R. Parts 170 through 189. Additional FDA guidance on its regulation of biocides used as food additives and food-contact substances can be accessed through the CFSAN Internet Home Page, www.cfsan.fda.gov/.
4.2
Regulation of Biocides in the United States 4.2.1
Regulation of Biocides Generally
The term “biocides,” as used herein, refers to pesticides covered by the European Union’s Biocides Product Directive (BPD). In the US, there is no formal recognition of biocides as a distinct group of pesticides with separate authorizing legislation, regulations, or regulatory authority. It is important to know the specific use to which a biocidal product will be put to determine the statutory and regulatory scheme(s) that will apply. Table 4.1 is a listing of the BPD product categories and provides a brief description of the manner in which each category is regulated in the US.
4.2.2
Regulation of Antimicrobial Biocides
One section of the FQPA amendments to FIFRA in 1996 [15] required EPA to establish review time frames or “goals” for the completion of action by EPA on applications for antimicrobial registrations and amendments [16], and to establish registration procedures [16a] and data requirements specific to antimicrobials [16b]. There are no statutory review time goals for registration actions for other types of biocides, except that EPA action on a “me-too” application, discussed in detail in Section 4.3.2.4, is to be completed within 90 days [17]. An “antimicrobial pesticide” is defined as “a pesticide (A) that is intended to (i) disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms; or (ii) protect inanimate objects, industrial processes or systems, surfaces,
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4 Regulation of Biocides in the United States Tab. 4.1.
EU BPD biocide categories and US regulatory equivalents
EU Product Category
US Regulatory Status
1. Human hygiene biocidal products (for use on the human body)
Regulated as cosmetics and/or drugs by the FDA under FFDCA
2. Private area and public area disinfectants, and other biocides (nonfood contact)
Regulated as antimicrobial pesticides by EPA under FIFRA
3. Veterinary biocidal products (for use in housing, transport, etc.)
Regulated as antimicrobial pesticides by EPA under FIFRA
4. Food and food area disinfectants and sanitizers
Jointly regulated by EPA under FIFRA as pesticides and by FDA under FFDCA as food additives, when used in process waters in food processing facilities Regulated solely by EPA as pesticides under FIFRA and FFDCA Section 408 when used on food-contact surfaces in food processing facilities. Regulated solely by EPA as pesticides under FIFRA when used on food-contact surfaces in residences (however, EPA might apply requirements consistent with FFDCA Section 408). (See Section 4.4.5 for discussion.)
5. Drinking water disinfectants
Jointly regulated by EPA Office of Pesticide Programs as antimicrobial pesticides under FIFRA and by EPA Office of Drinking Water under Safe Drinking Water Act
6. In-can preservatives
Regulated by EPA under FIFRA as antimicrobial pesticides; if used in materials potentially in contact with food (for example, preservative in adhesives used in food packaging), also regulated by FDA under FFDCA Section 409 as indirect food additives (See Section 4.4.4 for discussion.)
7. Film preservatives
Regulated by EPA as antimicrobial pesticides
8. Fiber, leather, and polymerized materials preservatives
Regulated by EPA as antimicrobial pesticides; if used as preservatives in components of articles in contact with food (for example, conveyor belt in food processing plant), also regulated by FDA as indirect food additives (See Section 4.4.4 for discussion.)
9. Wood preservatives
Regulated by EPA under FIFRA as antimicrobial pesticides or conventional pesticides, depending on target pest
10. Masonry preservatives
Regulated by EPA under FIFRA as antimicrobial pesticides
11. Preservatives for liquid-cooling and processing systems
Regulated by EPA under FIFRA as antimicrobial pesticides
12. Slimicides
Regulated by EPA under FIFRA as antimicrobial pesticides; if used in the production of food-contact paper or paperboard, also regulated by FDA under FFDCA Section 409 as indirect food additives (See Section 4.4.4 for discussion.)
13. Metalworking fluid preservatives
Regulated by EPA under FIFRA as antimicrobial pesticides
14. Rodenticides
Regulated by EPA under FIFRA as conventional pesticides
4.2 Regulation of Biocides in the United States Tab. 4.1.
EU BPD biocide categories and US regulatory equivalents (Cont.)
EU Product Category
US Regulatory Status
15. Avicides
Regulated by EPA under FIFRA as conventional pesticides
16. Molluscicides
Regulated by EPA under FIFRA as conventional pesticides
17. Piscicides
Regulated by EPA under FIFRA as conventional pesticides
18. Insecticides, acaricides
Regulated by EPA under FIFRA as conventional pesticide.
19. Repellants and attractants
Regulated by EPA under FIFRA as conventional pesticides
20. Preservatives for food and feedstocks
Regulated by FDA under FFDCA Section 409 as direct food additives
21. Anti-fouling products
Regulated by EPA under FIFRA as antimicrobial pesticides or conventional pesticides, depending on target pest
22. Embalming and taxidermy fluids
Not federally regulated in US
23. Vertebrate control products
Regulated by EPA under FIFRA as conventional pesticides
water, or other chemical substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, algae, or slime....” [18]. However, there are important exceptions to the types of antimicrobials that are subject to the antimicrobial reform provisions. All antimicrobials used in food or in contact with food are excluded from the definition. Moreover, wood preservatives and antifoulants that make claims against pests other than, or in addition to, microorganisms are excluded*. Applications for registration of antimicrobials that meet the statutory definition are to be reviewed within specified time frames. * * * *
* *
540 days for a new antimicrobial active ingredient; 270 days for a new antimicrobial use of a previously registered active ingredient; 120 days for any other new antimicrobial product; 90 days for substantially similar or identical (“me-too”) products (discussed in more detail in Section 4.3.2.4); 90 days for amendments that do not require scientific review of data; and 90 to 180 days for other types of amendments. [19]
No other pesticides are subject to review time goals. *
FIFRA § 2(mm)(1)(B); 7 U.S.C. 136(mm)(1)(B) [18a], excludes from the definition any antimicrobial subject to FFDCA § 408 [11] or § 409 [12]. FIFRA § 2(mm)(2); 7 U.S.C. 136(mm)(2) [18b] excludes wood preservatives and antifoulants. Wood preservatives, despite being exempt from the statutory definition of an
antimicrobial pesticide, are to be reviewed by EPA within the antimicrobial time frames if the data required to support the registration are the same as those required to support an antimicrobial pesticide. FIFRA § 3(h)(3)(E); 7 U.S.C. 136a(h)(3)(E) [18c].
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The 1996 Amendments directed EPA to promulgate regulations consistent with the statutory goals for completing antimicrobial actions within nine months of August 1996, the date of enactment of the new provision [20] Despite this statutory mandate, regulations have not yet been finalized as of the time of this writing. When issued, the regulations for antimicrobial registration actions will be codified at 40 C.F.R. Part 152 Subpart W[21]. In the meantime, the Antimicrobial Division has committed to process registrations subject to statutory deadlines within the prescribed time frames. It is important to note that EPA may conclude at the end of a specified review period that there are deficiencies in the application. In these instances, the applicant is required to address the deficiencies, usually by providing additional information or data, or revising administrative forms or labeling. In such instances the review time for the revised application is the same time period as that originally assigned.
4.3
Registration of a New Active Ingredient
EPA generally requires that a new active ingredient is registered before it can be used to formulate end-use products. As part of the application process, the following administrative forms must be submitted: Application for Registration (EPA Form 8570-1), Confidential Statement of Formula (EPA Form 8570-4), Certification with Respect to Citation of Data (EPA Form 8570-34), and public and EPA copies of the Data Matrix (EPA Form 8570-35). The proposed product label also must be submitted with the application package [22].
4.3.1
Active Ingredient Data Requirements
A complete set of data required to support the technical or pure grade of the active ingredient, otherwise known as “generic data,” must be submitted with the application package. A complete data package typically includes product chemistry data, acute, subchronic and chronic toxicity data, human exposure data, environmental fate data, ecotoxicity data, and residue data when the pesticide is to be registered for a food use. The toxicology database typically required for biocides, including antimicrobials (both food and nonfood-contact sites) that have a potential for high exposure, is referred to as a full “CORT” (Chronic, Oncogenicity, Reproductive and Teratogenicity) database. (Examples of high-exposure antimicrobial uses include swimming pool treatments, human and animal drinking water treatments, and aquatic outdoor uses such as ponds and irrigation ditches.) As a starting point, generally one should
4.3 Registration of a New Active Ingredient
refer to the data tables at 40 C.F.R. Part 158 for specific requirements. The data requirement regulations in the Code of Federal Regulations at the time this chapter was prepared (2001) were promulgated in 1984, and may not reflect current requirements. Any party considering preparing an application for registration of an active ingredient should consult with representatives of the respective EPA OPP Division (either the Registration Division or Antimicrobial Division, as appropriate) well in advance of finalizing a data package. EPA encourages these “pre-registration” meetings and typically requests that a prospective registrant prepare product labeling and other information that will enable its staff to determine appropriate data and other requirements for completing an application package. Testing submitted in support of registration must be performed to EPA Pesticide Assessment Guidelines (PAGs)[23] or equivalent standards and in compliance with EPA’s Good Laboratory Practice Standards (GLPs) [24]. EPA has been working on revising its data requirement regulations for almost a decade. The plan to publish a proposed regulation with updated data requirements has been delayed, but new regulations may be proposed in 2002. Antimicrobial Active Ingredient Data Requirements Data requirements for some antimicrobial pesticides differ from other biocides and agricultural pesticides. In 1987, EPA initiated a policy of “tiered” toxicology data requirements for antimicrobials, based on the potential exposure from their approved uses. The current (2001) interim OPP policy requires different “Tier I” or minimum databases for low-exposure antimicrobials, depending on whether registered for foodcontact or nonfood-contact use sites. (Antimicrobials with high-exposure uses are regulated in a manner consistent with other biocides with respect to data requirements, as discussed in Section 4.3.1.1, supra.)[25]. For low-exposure, food-contact uses, the “Tier I” toxicology data set includes an acute toxicity battery (acute oral, dermal and inhalation toxicity; eye and dermal irritation and dermal sensitization), two subchronic (90 day) oral toxicity studies, teratogenicity (onespecies), a mutagenicity battery and a two-generation reproductive toxicity study. Examples of indirect food-contact uses include hard surface sanitizers and slimicides used in manufacturing food-contact paper products. According to the current (2001) OPP interim policy, when the residue concentrations from indirect food contract use exceeds 200 parts per billion (ppb), the full CORT toxicity database described in Section 4.3.1, is required [26]. EPA currently requires more limited toxicity data for low exposure, nonfood-contact uses of antimicrobials. The “Tier I” database includes an acute toxicity battery, one 90 day study (usually by most common route of exposure), teratogenicity (one species) and a mutagenicity battery. Examples of low exposure uses include nonfood-contact material preservatives [27]. 4.3.1.1
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Follow-on Registration of an Active Ingredient In general, follow-on registrants of active ingredients are required to meet the same data requirements imposed on the original registrants of active ingredients. The requirements may be met by generating an additional, complete data package or by offering to compensate the original data submitter(s) for reliance on its (their) data [28]. Data protection and compensation are discussed in greater detail in Section 4.6. 4.3.1.2
4.3.2
Registration of End-use Product Formulations
FIFRA requires that each end-use pesticide formulation be registered prior to distribution or sale. Under most circumstances the formulated product is composed of one or more registered active ingredients and one or more “inert” (nonpesticidally active) ingredients. The application package consists of administrative forms, labeling, and product-specific data. The Application for Registration and Confidential Statement of Formula are the same forms used for an application for an active ingredient registration discussed earlier. Formulated Products Entitled to Formulator’s Exemption When a formulator of the end-use product purchases a registered active ingredient for use in the formulated product, it is entitled to a “formulator’s exemption.” Formulator’s exemption enables an applicant to obtain a registration without offering to compensate the original data submitter(s) for reliance on generic data [29]. The Formulator’s Exemption Statement (EPA Form 8570-27) must be submitted with the application package [30]. 4.3.2.1
4.3.2.2 Formulated Products Not Entitled to Formulator’s Exemption
In instances where the formulator of the end-use product is also the registrant of the active ingredient, EPA does not permit use of the formulator’s exemption. The applicant must complete a Certification with Respect to Citation of Data and Data Matrix. These forms must be consistent with the Certification and Data Matrix submitted in support of the active ingredient registration [31]. A registrant using an active ingredient from an unregistered source in its product formulation is responsible for satisfying all generic data requirements for the active ingredient. Consistent with the requirements for an applicant seeking a follow-on registration for an active ingredient (Section 4.3.1.3), either a complete data package must be submitted or applicable data must be cited and compensation offered. The Certification with Respect to Citation of Data and Data Matrix must be completed whether new data are submitted or existing data are cited. See the discussion at Section 4.6 for additional information.
4.3 Registration of a New Active Ingredient
4.3.2.3 Product-specific Data
Product-specific data necessary to support each new end-use formulation include product chemistry data and acute toxicity data, and efficacy data when the product’s label makes public health claims [32]. EPA requires the submission of efficacy data for all antimicrobial products that make public health claims, rodenticides, and some mammalian repellants. Insecticides and other biocides that make public health claims also may be required to submit efficacy data, although EPA has not consistently required efficacy data for these products. Even when EPA does not require submission of efficacy data, such data must be generated by the registrant, maintained in its files and submitted to EPA upon request [33]. 4.3.2.4 Applications for Formulated Product “Me-too” Registrations
The most common end-use registration is known as a “me-too” registration [34]. To qualify as a me-too, the formulation must be identical or substantially similar to another registered pesticide product in amount and identity of active ingredients, amount and identity of inert ingredients, use patterns, and use directions. FIFRA requires that EPA notify an applicant within 45 days as to the completeness of the me-too application. If the application is complete, EPA has 90 days in which to notify the applicant whether it has been approved [35]. EPA makes the ultimate determination whether the product is, in fact, identical or substantially similar by reviewing the Confidential Statement of Formula submitted for the me-too application and the Confidential Statement of Formula for the product referenced by the applicant. The requirements for me-too classification are strictly applied and many products do not qualify. Examples of products that do not qualify include products with: different active ingredient; registered active ingredient at a different percentage; significantly different inert ingredients; or similar inerts at a different percentage; new formulation type; label with different pests; different dose rates or different frequency of application or use. An application for a technical or manufacturing use product is not granted me-too status, because, at a minimum, the follow-on registrant of a technical or manufacturing use product must submit manufacturing process data, batch analyses, and physical and chemical characteristics. The submission of data requires EPA to conduct data reviews and eliminates the application from expedited processing.
4.3.3
Amendments to Change Existing Registrations
Once a pesticide product has been registered, the registrant may have to submit an application for amendment in order to make changes to the product’s formulation or the product’s labeling. The contents of an application for amendment depend on the
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type of change proposed. An application form must be submitted, identifying the nature of the change sought by the amendment. A Confidential Statement of Formula must be submitted if a change is proposed to the formula. Draft revised labeling must be submitted if a labeling change is sought. Data may be required, depending on the nature of the amendment [36].
4.3.4
Changes Not Requiring Amendments
EPA permits some limited types of labeling, formulation, or other changes by use of notification, rather than amendment [37]. The advantage to availing oneself of the ability to notify is that the change being notified may be implemented by the registrant coincidentally with submission of the notification to EPA. The one exception to this rule is that FIFRA requires that any change in the labeling of an antimicrobial pesticide is subject to a 60 day waiting period or approval of the notification by EPA, whichever occurs first [38]. A registrant must certify that the notification complies with all EPA requirements and that no other changes have been made to labeling or the formula [39]. Some other minor changes may be made to the pesticide label without notifying EPA [40]. They include correction of typographical or printing errors, and change in name or address of the registrant, except those that involve change in ownership, and redesign of the label format. These are examples only; other minor changes may be permitted, but EPA’s regulations and guidance should be consulted for further information.
4.4
Regulation of Biocides Used in, on, or in Contact with Food 4.4.1
EPA Regulation of Pesticide Chemicals in or on Food
FFDCA provides the authority for regulating residues of substances in food. Section 408, administered by EPA, regulates “pesticide chemical residues” in food. When seeking registration of a pesticide chemical that will result in residues in or on food, a party must apply for both a registration pursuant to FIFRA Section 3 and submit a petition for a tolerance or exemption from tolerance pursuant to FFDCA Section 408. A tolerance is the legal limit of a residue that may be present in a specified food or food group, promulgated as a regulation and published in the Code of Federal Regulations [41]. An exemption from tolerance is a determination by EPA that the total
4.4 Regulation of Biocides Used in, on, or in Contact with Food
amount of the pesticide chemical in food, under prevailing conditions of use, involves no hazard to public health. Exemptions from tolerance are published as regulations by EPA [42].
4.4.2
FDA Regulation of Food Additives
Section 409, administered by FDA, regulates “food additives,” substances resulting or reasonably expected to result in being a component of food as a result of their intended use [43]. A food additive petition may be required for a biocide proposed for a foodcontact use [44]. FDA reviews the petition and makes a determination whether the showing of safety by the petitioner is adequate. If approved, a regulation is published providing for the general use of the substance for the specified food-contact use [45].
4.4.3
FDA Regulation of Food-contact Substances
Alternatively, a party may determine it is appropriate to prepare a Premarket Notification (PMN) for a food-contact substance [45a]. This regulatory category, defined as “any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have a technical effect on food,” was created by amendments to FFDCA in 1997. FDA has 120 days from date of receipt to object to the notification, thereby preventing marketing of the FCS. If FDA determines the safety assessment prepared by the notifier is adequate and no objection is filed within 120 days, the substance may be marketed. In contrast to the general applicability of a food additive regulation, the notification is proprietary to the manufacturer listed in the notification [46].
4.4.4
Overlapping EPA and FDA Jurisdiction for Antimicrobial Food-Contact Uses
FQPA, because of an inadvertent drafting error, transferred jurisdiction for antimicrobials, which historically had been regulated as food additives by FDA under FFDCA Section 409, to EPA as “pesticide chemical residues” subject to regulation under FFDCA Section 408 [47]. In 1998 ARTCA was enacted and partially restored jurisdiction for food-contact antimicrobial pesticides to FDA, while also continuing EPA’s regulatory authority for these compounds [48]. The result is a complex scheme of both separate and shared responsibility for antimicrobial food-contact uses between EPA and FDA.
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A brief summary (Tables 4.2 and 4.3) of the FFDCA jurisdictional provisions, as amended by ARTCA, is provided below [49]. However, the jurisdictional distinctions are complex and an interested party should consult with legal advisors and/or the two agencies to determine the appropriate regulatory programs applicable to a particular food-contact use of an antimicrobial pesticide. Table 4.2
Examples of antimicrobials regulated by EPA and FDA.
*
Antimicrobial applied to water that contacts food in facilities where food processing occurs [50]
*
*
Antimicrobial preservative that is a component of an article with food contact, but in which the antimicrobial has no intended ongoing effect on the article or on the article’s food-contact surface (for example, a preservative of the plastic or latex incorporated into a piece of equipment used in a food processing facility.) [54] Antimicrobial used in food packaging material (for example, slimicides used in pulp and paper mills in the wet-end of paper and paperboard production and preservatives in food-contact paper coatings.) [52]
*
*
Tab. 4.3.
*
Dually regulated by FDA as a food additive (either indirect or secondary direct) under FFDCA Section 409 and by EPA as a pesticide under FIFRA Dually regulated by FDA as a food additive (either indirect or secondary direct) under FFDCA Section 409 and by EPA as a pesticide under FIFRA.
Dually regulated by FDA as a food additive (either indirect or secondary direct) under FFDCA Section 409 and by EPA as a pesticide under FIFRA
Examples of Antimicrobials Regulated Solely by EPA.
*
Antimicrobials used on permanent and semipermanent surfaces (for example, a hard-surface sanitizer) [53]
*
*
Antimicrobials in treated articles marketed with claims that the antimicrobial is intended to have a pesticidal effect on the food-contact surfaces [54]
*
*
Antimicrobials and other pesticide products applied on raw agricultural commodities (RACs) and for which there is no processing in the field or in facilities receiving the RACs [55]
*
EPA, as a result of ARCTA’s enactment, now has sole jurisdiction for the regulation of antimicrobials used on permanent and semipermanent surfaces (e.g., surfaces of equipment that contact food). These uses are subject to registration under FIFRA and to the tolerance or tolerance exemption requirements of FFDCA Section 408 EPA has sole jurisdiction for regulating antimicrobials used in treated articles making pesticidal claims. The treated articles could be subject to the tolerance and tolerance exemption requirements of FFDCA Section 408. EPA retains its historic sole jurisdiction. These pesticides are subject to the tolerance and tolerance exemption requirements of FFDCA Section 408
A party wanting to market an antimicrobial pesticide also subject to regulation by FDA as a food additive or a food-contact substance, must comply with FDA’s requirement separately from the EPA registration action. Either a petition for a food additive regulation or a premarket notification (PMN) for a food-contact substance must be
4.4 Regulation of Biocides Used in, on, or in Contact with Food
prepared and submitted to the FDA Center for Food Safety and Applied Nutrition, (CFSAN), Office of Food Additive Safety. (The specific FDA requirements and procedures for obtaining a regulation permitting use of the substance as a food additive or preparing and submitting a PMN are not discussed in this article.) Additional information is available through the FDA CFSAN Internet Home Page, www.cfsan.fda.gov. Compliance with FDA requirements pursuant to FFDCA Section 409 does not enable a party to market the subject biocide product. It also must be registered by EPA before it can be sold or distributed as a pesticide and the FDA-regulated use must be explicitly referenced on the product’s label. EPA at the present (2001) has interpreted its statutory responsibility as requiring it to assess food-contact antimicrobial pesticides consistent with FQPA risk assessment provisions and independent of any FDA action, prior to issuing a FIFRA registration [56]. These EPA assessments are in addition to FDA’s reviews and decisions and may result in different regulatory standards (that is, permissible residue levels) for the same uses or even conflicting regulatory conclusions. FQPA requires EPA to aggregate all anticipated risks from dietary exposure, exposure resulting from occurrence of the pesticide in drinking water, and exposure from residential and other nonoccupational uses. FQPA also requires EPA to consider whether an additional ten-fold safety factor, intended to protect infants and children, should be imposed, reduced, eliminated, or even increased in completing the risk assessment for the final regulatory decision on the pesticide. See Section 4.5.2 for additional discussion of FQPA risk assessments.
4.4.5
EPA Identification of Biocides as Food Contact
Historically, the determination of whether a pesticide’s uses were considered food or nonfood contact depended on its use consistent with the requirements of FFDCA Section 408 or 409. There are indications that EPA in the future may regard certain biocide uses, which are not considered by FDA to be food-contact uses and are not regulated pursuant to FFDCA, as subject to regulation consistent with the FQPA safety standards for pesticides used on food. Examples of such uses could include disinfectants used on hard surfaces and followed by potable water rinses, sanitizers used on food surfaces in residences, and insecticides used in food processing facilities for crack and crevice treatment. These uses have not previously been considered food uses. A prospective registrant should seek clear guidance from EPA during a pre-registration meeting, not only on the data that will be required for registration, but also on the risk assessment criteria that will be used for the registration review.
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4.5
Pesticide Re-registration 4.5.1
Expedited Re-registration
In 1988 Congress amended FIFRA to require EPA to re-register (re-evaluate) all pesticide products containing any active ingredient registered prior to 1984. The re-registration process was to be “expedited” and completed by fiscal year 1997 [57]. That completion date was extended on several occasions to 2002 and now has been extended to 2006. EPA was directed to bring all databases supporting pesticide registrations to current standards. When the amendments were enacted, the standards were considered to be consistent with the data requirements at 40 C.F.R. Part 158, which were finalized in 1984. Data call-ins (see Section 4.8.1) were issued for these active ingredients with existing databases that did not meet 1984 requirements. To re-register pesticides, EPA evaluates the risks posed by each active ingredient and each use of the active ingredient to make a re-registration decision. Active ingredients may not qualify for re-registration; in other instances, some uses of a particular active ingredient may not be re-registered. Frequently, risk mitigation measures are imposed in order for the active ingredient to be re-registered. Examples of risk mitigation have included reduction in use rates, increased requirements for personal protective equipment to be worn by applicators, and extended periods before re-entry to a treated area is permitted. EPA’s extensive review of the use, chemistry, toxicology, environmental, and ecological impacts, and the resultant risk assessments are published in a Re-registration Eligibility Decision (RED) document [58]. Following EPA’s comprehensive review of each active ingredient and publication of the RED document, each end-use formulation containing the active ingredient also must be re-registered. End-use product re-registration involves updating product-specific chemistry, toxicity, and where required, efficacy data, and revising the label to be consistent with the decisions and limitations in the RED.
4.5.2
Tolerance Reassessment
The re-registration process was changed by the passage of FQPA and its requirement that EPA reassess all existing tolerances and exemptions from tolerance by 2006 [58a]. Re-registration is being conducted in conjunction with the tolerance reassessment activities. As a result, all re-registration decisions involving pesticides regulated under both FIFRA and FFDCA Section 408 now must take into consideration the new risk assessment criteria established by FQPA. The risk assessment factors introduced by
4.6 Data Protection and Data Compensation Procedures
FQPA are: application of an uncertainty factor of ten (which may be eliminated, maintained, reduced, or increased); aggregation for a single active ingredient of all exposures from dietary, drinking water, and residential and other nonoccupational sources; and cumulative risk assessments when EPA determines that a group of active ingredients has a common mechanism of toxicity. FQPA also requires the evaluation of the endocrine disrupter effects of pesticides and other chemical compounds. EPA is currently developing its program, which will apply to all chemical compounds, and it is not discussed further in this chapter.
4.5.3
Fifteen Year Registration Review
FQPA added a provision to FIFRA requiring EPA to publish regulations for procedures to accomplish the periodic (every 15 years) review of existing registrations [59]. An Advanced Notice of Proposed Rulemaking (ANPR) was published on April 26, 2000 for public comment [60]. The ANPR was very preliminary and sought recommendations from the public. Numerous issues are raised by this statutory requirement and are unresolved at this time, including how to determine the date on which to base the 15-year review period for any active ingredient, priorities that should be established for the order in which active ingredients are reviewed, and how to handle nonconventional chemicals, including antimicrobials and possibly other biocide categories. EPA has provided no indication about when proposed regulations to implement periodic reregistration will be published for public review and comment.
4.6
Data Protection and Data Compensation Procedures
Pesticides regulated pursuant to FIFRA are subject to “exclusive use,” mandatory data citation and compensation, and binding arbitration requirements. Exclusive use protection is provided for new active ingredients for a period of ten years following the date of the first registration of a new active ingredient. During the period of exclusive use, data may not be cited by another registrant without the written consent of the original data submitter [61]. Outside this period of exclusive use, FIFRA provides that data may be cited without the permission of the original data submitter to support various types of pesticide applications. Data citation is not a free ride, but a form of mandatory licensing. Under FIFRA, data are compensable for a period of 15 years following the date of their first submission to EPA and may be cited in support of an application for initial registration by a follow-on registrant, an experimental use permit (EUP), an amendment to an
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existing registration or application for a new registration adding a new use to an existing active ingredient registration, and for re-registration [62]. The mandatory data citation rights granted by FIFRA are limited to federal registrations. Individual states may require the submission of data before a registration or license is granted by the state. Such state requirements are outside the scope of FIFRA’s mandatory data citation provisions. For example, the California EPA Department of Pesticide Regulation (CDPR) requires applicants to provide copies of all data submitted to US EPA OPP, which it independently reviews to make its own registration decisions [63]. CDPR does not recognize offers of compensation made under FIFRA and an applicant must obtain the right to rely on another party’s data, to the extent required by CDPR, separate from the offer of compensation pursuant to FIFRA [64]. See Section 4.12 for additional information on state pesticide registration requirements and procedures. The mandatory data citation provisions similarly do not provide any party citing the data with copies of the cited data. EPA is required to make health and safety data generated by a registrant in support of a pesticide available to the public [64]. However, EPA is prohibited from disclosing information submitted by a registrant or applicant in support of a registration, to the employee or agent of a foreign or multinational pesticide producer [64b]. This provision is intended to prevent use of studies obtained from EPA in support of registration in another jurisdiction, in circumvention of FIFRA data protection and compensation provisions. It is possible for individual parties to negotiate an agreement whereby the original data submitter provides a hard copy of the data to the party offering compensation, along with the right to use the data for purposes of obtaining registrations in other nations or jurisdictions. However, such actions are outside the scope of and not required by FIFRA’s data citation provisions.
4.6.1
Procedures for Compliance with Data Protection and Compensation Requirements
An applicant may cite data other than exclusive-use data, without the permission of the original data submitter, as long as the applicant has made an offer of compensation to the original submitter(s). FIFRA requires that the applicant submit a copy of the offer to EPA along with proof of delivery. EPA has implemented this provision by requiring that an applicant submit with its application a Certification With Respect To Citation Of Data, certifying that an offer of compensation has been made or that permission has been granted [65]. In general, there are two types of compensation offers. The first is the “cite-all” method, by which the follow-on registrant cites all data on file with EPA for a particular active ingredient [66]. The advantage to using the cite-all method is that it is the
4.6 Data Protection and Data Compensation Procedures
most expeditious to obtaining a registration. EPA does not conduct a review of the data or perform a risk assessment in order to reach a registration decision, instead relying on its previous registration decisions. The principal disadvantage to the data cite-all method is that the data citer may well have to pay more in compensation than if using the selective method. For example, the data citer may have to agree to provide compensation to multiple parties or for multiple studies satisfying a particular guideline requirement. Use of the cite-all method also may result in the data citer being required to pay compensation for studies that are not needed for the uses it seeks to register. The other general type of compensation offer is the “selective” method of citation. One uses the selective method when only specific studies are cited. For example, where multiple studies have been submitted for a single guideline, the selective citer may cite only one. A selective citer also can limit its compensation offer to those studies that are required to support a particular use, not all the uses that have been registered by the original data submitter and for which data are on file with EPA [67]. The major drawback to the selective method of citation is that EPA must determine whether all the data cited would be sufficient to conduct a risk assessment that supports the uses of the follow-on registrant. Because EPA must make an independent risk assessment decision, the selective method of citation often leads to significant delays. Follow-on registrants also may follow a hybrid data strategy–submitting some studies and using the “selective cite-all” method for particular guideline requirements [67a]. When using selective cite-all, a follow-on registrant may submit its own data and/or selectively cite studies to fulfill certain guideline requirements, but, for other guideline requirements, cite all data on file satisfying those particular guidelines.
4.6.2
Compensation Offers and Arbitration
A valid offer of compensation must include an offer to submit to binding arbitration in the event that agreement on the amount of compensation or other terms cannot be reached. EPA’s regulations on the cite-all, selective, and selective cite-all methods of offering compensation provide detailed guidance on the contents of a valid offer letter for each method. Any party to a data compensation proceeding may initiate binding arbitration if agreement has not been reached within 90 days following receipt of the original compensation offer. Arbitration is conducted under the American Arbitration Association rules for commercial arbitrations. Parties may elect to have either one or three arbitrators. The parties to the arbitration must share the costs of the arbitration, including
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fees charged by the arbitrator(s). An arbitration decision is final and cannot be appealed to a court unless fraud has been perpetrated in the course of the arbitration [68]. Arbitration decisions are not made public on a routine basis. Parties to an arbitration may elect to make portions of a decision public. However, arbitration decisions provide no legal precedents. Each arbitration decision stands on its own merits. Because there is a lack of precedent, there are no general standards that apply to arbitrations.
4.6.3
EPA’s Role in Data Compensation
EPA acts to ensure that it has received appropriate certification of the manner in which a follow-on registrant has satisfied applicable data citation and compensation requirements. If EPA believes that it has received all necessary certifications, it does not independently determine that all appropriate offers have been made. Moreover, EPA does not participate in negotiations or arbitration proceedings and takes no position on the appropriate amount of compensation. If a registrant believes that another party has cited its data without making a proper offer to pay, the registrant has one year in which to petition EPA to cancel the registration [69]. If EPA determines that a data citer failed to make a valid offer, to negotiate in good faith, to participate in binding arbitration or to pay an award, EPA may cancel the registration [70].
4.6.4
Data Call-ins and Offers to Jointly Develop Data
EPA is authorized to require additional data to be submitted in support of an existing registration. When EPA issues such a requirement, known as a “data call-in,” and there are two or more registrants of the existing active ingredient, the statute provides for the joint development of the data. Joint data development is not mandatory, but is encouraged. When data are jointly developed, registrants offer to jointly support development of such data. Offers to jointly develop data are similar to those made by follow-on registrants; however, such offers are irrevocable. If the registrants fail to agree on the terms of a joint data development arrangement, any party subject to the data call-in may initiate binding arbitration [71].
4.7 EPA Regulation of Pesticide Inert Ingredients
4.6.5
Data Protection and Compensability under FFDCA for Active and Inert Ingredients
As discussed in Section 4.4.1, EPA requires information on the residues of pesticides in food pursuant to FFDCA Section 408. FQPA granted EPA the authority to provide exclusive use and data compensation protection for data required under FFDCA to the same extent provided by FIFRA [72]. EPA is currently working to implement this provision to FFDCA. To the extent that the same data are required for the registration of an active ingredient and to support tolerance petitions, data protection and compensability already are assured under FIFRA. Implementing a new system primarily impacts inert ingredients that are subject to the tolerance requirements of FFDCA.
4.7
EPA Regulation of Pesticide Inert Ingredients
Following the publication of a 1987 policy statement, EPA divided inert ingredients into categories or “lists” in an effort to prioritize them for testing or other regulatory action. The lists are publicly available at http://www.epa.gov/opprd001/inerts/, but have not been updated in several years and may not be complete. The categories are: *
* * * *
List 1 “Inert Ingredients of Toxicological Concern” (registrants with formulations containing at least one inert ingredient from this list have been required to substitute with another inert ingredient or to amend the label to name the “toxic” inert ingredient and satisfy the requirements EPA has required through the issuance of a data call-in); List 2 “Potentially toxic inert ingredients with high priority for testing.”; List 3 Inerts of “unknown toxicity”; List 4A Inerts of “minimal concern”; List 4B Inerts for which EPA has determined it has sufficient information to conclude that the current use does not adversely impact human health or the environment [73].
EPA ultimately intends to move all inert ingredients onto either List 1, List 4A, or List 4B. Many of the inert ingredients that are currently on List 3 have been “grandfathered”, that is, accepted for use at the present time based on use prior to 1987. As discussed in Section 4.5.2, supra, because EPA is now required to assess all tolerances and tolerance exemptions that have been previously issued for inert ingredients with food uses, the requirements articulated in its 1987 policy are being reassessed. EPA intends to publish a comprehensive policy statement on its risk assess-
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ment methodology for inert ingredients in 2002. In the meantime, it has begun to use the methodology for clearances [73a]. The total percentage of all inert ingredients in a pesticide formulation is contained in the ingredient statement on a pesticide label, along with the percentage of each individual active ingredient. However, FIFRA does not require individual inert ingredients to be named on the label. In fact, information on the identity or the percentage quantity of any deliberately added inert ingredient in a pesticide is exempt from disclosure “unless [EPA] has first determined that disclosure is necessary to protect against an unreasonable risk of injury to health or the environment” [74].
4.8
Registrants’ Continuing Obligations
4.8.1
Data Call-ins
EPA is authorized to require additional data to maintain a pesticide’s existing registration. To do so, EPA notifies all registrants of a product that contains a particular active (or inert) ingredient, using a “data call-in” (DCI). A DCI provides a list of all data that are to be generated and, in the case of an active ingredient, a list of all parties receiving the data call-in. Each registrant has 90 days in which to respond. Two or more registrants may agree to share in the cost of developing the necessary data, as discussed in Section 4.4.4. If the registrants fail to agree on terms for sharing the costs of data development within 60 days of receipt of the DCI, any of the registrants may initiate binding arbitration [75]. If a registrant does not wish to generate data, in its response to the DCI it will be required to voluntarily cancel its registration(s) containing the affected ingredient. Such registrant is usually granted a specified period of time during which it may sell its existing stocks of the product(s). If a registrant does not respond to the data call-in within the requisite time, EPA is authorized to issue a Notice of Intent to Suspend (NOIS). A registrant may request a hearing to contest the NOIS. If it has not done so within 30 days, the suspension is final and effective. EPA may establish an existing stocks period that it deems appropriate in such cases [76].
4.8 Registrants’ Continuing Obligations
4.8.2
Reporting Adverse Effects Information
FIFRA requires that “[i]f at anytime after registration of a pesticide the registrant has additional factual information regarding unreasonable adverse affects on the environment of the pesticide, the registrant shall submit such information to [EPA]” [77]. EPA has promulgated complex comprehensive regulations to implement this provision [78]. The agency also has issued a number of PR Notices to further clarify its interpretation of this provision and its regulations [79]. The regulations cast a very broad net in terms of the information that must be reported. First, it broadly defines a “registrant” and, in some cases, requires a former registrant to report adverse effects for a period of five years following cancellation or transfer of a pesticide. There is an indefinite reporting obligation for any product involved in product liability litigation [80]. Information potentially reportable includes laboratory studies, information about pesticide residues on food or feed or in water, information on metabolites, degradates, contaminants and impurities, toxic or adverse effects incident reports, and some failure of performance information. There is also an extremely broad “catch-all” provision requiring that a “registrant ... submit ... [any] information ... that EPA might regard ... as raising concerns about the continued registration of a product” [81]. The requirement for toxic or adverse effect incident reporting is extremely broad. As long as three conditions are met, the incident is considered to be reportable by EPA: * *
*
the registrant is aware or has been informed that exposure may have occurred; the registrant is aware or has been informed that a toxic or adverse effect has been alleged; the registrant has, or can obtain, information concerning where the incident occurred, the pesticide or product involved, and the name of a contact to whom to direct questions regarding the alleged incident.
Perhaps the most important aspect of EPA’s incident reporting standard is that any opportunity for a registrant to determine causation, that is, make a reasoned judgment that a causal relationship exists between an alleged exposure and an alleged effect, has been eliminated [82]. There is a complex process for categorizing exposure types and severity of effects, which impact how and when to report. The regulations also provide specific instructions on when toxicology, ecological, exposure, epidemiology and other studies trigger the reporting threshold. Adverse effects information acquired by foreign parents or subsidiaries, if directly relevant to a pesticide registered in the United States, is subject to EPA’s reporting requirements. Reporting deadlines run from 15 days for a repor-
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table fatality to 90 days for minor severity categories. EPA’s regulations and other guidance documents should be consulted when attempting to determine reporting obligations [83].
4.8.3
Other Reporting and Recordkeeping Requirements
Each domestic and foreign facility where a pesticide that enters US commerce is manufactured, formulated, packaged, repackaged, labeled, or relabeled must obtain an EPA establishment registration [84]. Registered establishments are provided unique establishment numbers. Registered establishments are required to annually report the volume of each pesticide produced in or exported to the US [85]. Registrants and all other producers of pesticides are required to maintain records of all pesticide production for two years. EPA’s regulations specify the information that must be maintained in the production records [86].
4.9
Pesticide Import and Export Requirements
EPA regulates the import and export of pesticides. Any importer of registered or unregistered pesticide to the United States must submit to the applicable EPA Regional Office, prior to arrival of the pesticide shipment, a “Notice of Arrival of Pesticide and Devices” (NOA). The EPA Regional Office completes the NOA and returns it to the importer. The importer then must present the NOA to the Customs Office at the port of entry. The explicit notification to EPA of each and every pesticide shipment affords the agency the opportunity to review shipments prior to their arrival. It also requires explicit EPA approval of entry for any unregistered pesticide. The imported registered pesticides must conform with EPA’s regulations, including all EPA-required pesticide labeling. EPA may refuse to admit a shipment that upon analysis does not conform to its declared contents and the registrant may be subject to enforcement action [87]. FIFRA permits EPA to regulate exports including labeling and pre-shipment requirements for unregistered pesticides. All exported pesticides must bear appropriate FIFRA labeling. The registrant or the distributor of the product is required to translate into the language of each country to which the distributor is aware the product will be sent. The elements of the pesticide label subject to the multilingual translation requirements are (i) the EPA pesticide producing establishment number, (ii) all warning or caution statements, (iii) a statement “Not registered for use in the United States,” if such statement is applicable, (iv) the ingredient statement, (v) the name of the producer, the registrant or other person for whom the pesticide was produced, and
4.10 Cancellation and Suspension
(vi) the product’s weight or measure. Translation of additional warning statements for certain highly toxic pesticides also may be required [88]. In addition, the distributor or shipper of an unregistered pesticide must obtain foreign purchaser acknowledgement prior to shipment. The statement from the foreign purchaser must explicitly acknowledge its understanding that the pesticide is not registered for sale or use in the United States. Information on shipments of unregistered pesticides must be reported to EPA by the exporter, on either a per shipment or annual basis. EPA transmits copies of all foreign purchaser acknowledgments to the applicable national authorities [89].
4.10
Cancellation and Suspension
EPA is authorized to cancel a registration only following issuance of formal notice to a registrant of its intent. The registrant must be afforded the opportunity to a hearing. At the hearing evidence is presented as to whether the standard for cancellation has been met, that is, either the pesticide or its labeling does not comply with FIFRA, or, “when used in accordance with widespread and commonly recognized practice, [the pesticide] generally causes unreasonable adverse effects on the environment”. EPA must consult with the Secretary of Agriculture, or in the case of a public health pesticide, the Secretary of Health and Human Services, 60 days prior to sending the notice to the registrant. The cancellation is final 30 days after receipt by the registration or publication, whichever occurs later, unless the registrant corrects the identified problems or requests a hearing [90]. EPA regulations govern the conduct of cancellation hearings [91]. Any party to the hearing, including the presiding EPA Administrative Law Judge (ALJ), may request review of relevant scientific facts by a committee of the National Academy of Sciences (NAS). EPA then is required to make a final decision based on evidence from the hearing and NAS report, if one has been requested [92]. A final EPA decision is subject to review by either a federal district court or federal court of appeals, depending on the nature of the order being appealed [92a]. EPA also is authorized to order the emergency suspension of a pesticide, if “necessary to prevent imminent hazard” during the cancellation proceedings. A registrant may request an expedited hearing within five days of the notice. Under certain circumstances, EPA may issue an emergency order prior to its issuance of the notice of cancellation [93]. EPA regulations provide rules of practice for conducting expedited hearings [94]. Suspension orders are reviewable by US courts, consistent with judicial review granted by FIFRA, even when the final cancellation proceeding applicable to the suspension has not been completed [95].
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4.11
EPA Enforcement Authority
EPA has a number of enforcement tools available to deal with violations of FIFRA [96]. EPA may issue an order to “stop sale, use, or removal” [97]. EPA also is authorized under the law to obtain a US district court order to seize the product, if unregistered, misbranded, adulterated, or otherwise in violation [98]. FIFRA also authorizes EPA to assess civil penalties for each separate offense [99]. A party has the right to contest the penalty in a hearing before an ALJ. Registrants and applicants “knowingly” violating any provision of FIFRA are subject to criminal prosecution under FIFRA. Penalties may include a fine or imprisonment for not more than one year, or both [100].
4.12
Pesticide Licensing in Individual States
Each state requires that a registrant obtain a state registration or license prior to the sale or distribution of a pesticide product within its borders. A license or registration is granted for a period of either one or two years. Fees ranging from US$ 20 to more than US$ 2000 are required with each initial registration and each subsequent renewal. The documentation required by each state varies. Most states issue registrations, but do not require submission or review of data. However, several states, including California, Florida, and Massachusetts, require submissions similar to those required by EPA and make registration decisions independent of EPA’s. A state is not authorized to register a pesticide not registered by EPA. However, a state may decline to register for sale within its borders a pesticide that has obtained EPA registration.
Abbreviations
ALJ: Administrative Law Judge ANPR: Advanced Notice of Proposed Rulemaking ARTCA: Antimicrobial Reform Technical Corrections Act BPD: European Union’s Biocides Product Directive CDPR: CalEPA (California Environmental Protection Agency) Department of Pesticide Regulation. More information is available at http://www.cdpr.ca.gov. CFR: Code of Federal Regulations CFSAN: FDA’s Center for Food Safety and Applied Nutrition. More information is available at www.cfsan.fda.gov. CORT: Chronic, Oncogenicity, Reproductive, and Teratogenicity data CSF: Confidential Statement of Formula DCI: Data Call-in
References
EPA: US Environmental Protection Agency. More information is available www.epa.gov. FCS: Food-contact Substance FDA: US Food and Drug Administration. More information is available www.fda.gov. FFDCA: Federal Food, Drug, and Cosmetic Act. More information is available www4.law.cornell.edu/uscode/21/ch9.html. FIFRA: Federal Insecticide, Fungicide, and Rodenticide Act. More information available at www.epa.gov/pesticides/fifra.htm. FQPA: Food Quality Protection Act of 1996. More information is available www.epa.gov/oppfead1/fqpa. FR: Federal Register GLPs: Good Laboratory Practice Standards NAS: National Academy of Science NOA: Notice of Arrival NOIS: Notice of Intent to Suspend OPP: EPA’s Office of Pesticide Programs. More information is available at www.epa.gov/pesticides. PAG: Pesticide Assessment Guidelines PMN: Premarket notification PR Notice: Pesticide Regulation Notice. More information is available at http://www.epa.gov/PR_Notices. RACs: Raw agricultural commodities RED: Re-registration Eligibility Decision. More information is available at www.epa.gov/pesticides/reregistration/status.htm. SRRD: EPA’s Special Review and Re-registration Division
at
at at is at
References
References
[1] Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. § 136 et. seq. [2] Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. § 321 et seq. [3] FIFRA § 3; 7 U.S.C. 136a. [4] FIFRA § 3(c)(1)(C); 7 U.S.C. 136a(c)(1)(C). [5] FIFRA § 4; 7 U.S.C. 136a-1. [6] FIFRA § 3(g); 7 U.S.C. 136a(g). [7] FIFRA § 12(a); 7 U.S.C. 136j(a). [8] FIFRA § 6(a)(2); FIFRA §§ 7, 8, and 9; 7. U.S.C. 136d(a)(2), 136e, 136f, and 136 g. [9] FIFRA § 3(c)(2)(B); 7 U.S.C. 136a(c)(2)(B). [10] FIFRA § 17; 7 U.S.C. 136o. [11] FFDCA § 408; 21 U.S.C. 346a.
[12] FFDCA § 409; 21 U.S.C. 348. [13] Food Quality Protection Act of 1996 (FQPA), Pub. L. 104-170, 1996. [14] Antimicrobial Regulation Technical Corrections Act of 1998 (ARTCA), Pub. L. 105-324, 1998. [15] FIFRA § 3(h); 7 U.S.C. 136a(h). [16] FIFRA § 3(h)(2); 7 U.S.C. 36a(h)(2). [16a] FIFRA § 3(h)(3)(A); 7 U.S.C. 36a(h)(3)(A). [16b] FIFRA § 3(h)(3)(A)(ii)(III); 7 U.S.C. 36a(h)(3)(A)(ii)(III). [17] FIFRA § 3(c)(3)(B); 7 U.S.C. 136a(c)(3)(B). [18] FIFRA § 2(mm)(1)(A); 7 U.S.C. 136(mm)(1)(A). [19] FIFRA § 3(h)(2); 7 U.S.C. 36a(h)(2).
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4 Regulation of Biocides in the United States [20] FIFRA § 3(h)(3); 7 U.S.C. 136a(h)(3). [21] Proposed regulations were published by EPA September 17, 1999 at 64 Federal Register (FR) 50671. Final regulations have not yet been promulgated. [22] EPA’s pesticide registration forms are available to be downloaded from EPA’s website, www.epa.gov/opprd001/forms/. A registration kit also is available at this site. EPA’s regulations on registration procedures are at 40 C.F.R. Part 152. [23] 40 C.F.R. § 158.108. [24] 40 C.F.R. Part 160. [25] EPA presented draft data requirements in 1997 to the FIFRA Science Advisory Panel for its review and recommendations. This draft is available on the Antimicrobial Division website (www.epa.gov/oppad001/ regpolicy.htm). The data requirements in this draft document reportedly have been revised and are not consistent with EPA’s current interim policy. However, the draft provides insight into EPA’s approach to requiring data for antimicrobial registrations. [26] EPA has not published any formal document describing its interim policy for antimicrobial data requirements. However, one articulation of the requirement for antimicrobial products intended for food-contact uses can be found in the Preliminary Risk Assessment for the active ingredient, 1,4-bis(bromoacetoxy)2-butene. The availability of this preliminary risk assessment was announced in the June 6, 2001 Federal Register. 66 FR 30460. [27] (www.epa.gov/oppad001/regpolicy.htm) The 1997 draft (see note[25]) for nonfoodcontact, low-exposure antimicrobials included in its Tier I database both acute neurotoxicity and immunotoxicity testing requirements. Reportedly, these data currently are not routinely required. [28] FIFRA § 3(c)(1)(F); 7 U.S.C. 136a(c)(1)(F). [29] FIFRA § 3(c)(2)(D); 7 U.S.C. 136a(c)(2)(D). [30] 40 C.F.R. § 152.85. [31] See generally 40 C.F.R. Part 152 Subpart E, Procedures to Ensure Protection of Data Submitters Rights. See also PR Notice 98-5, available at www.epa.gov/ opppmsd1/PR_Notices/.
[32] The applicant should consult the EPA pesticide data tables at 40 C.F.R. Part 158. The provision at 40 C.F.R. § 158.102 provides information on determining data requirements for manufacturing or technical products and end-use products. [33] 40 C.F.R. § 158.690. In particular, refer to footnote 1 following the data table. [34] Me-too registration procedures are not addressed in EPA’s regulations at this time. Information on preparation of me-too applications and criteria for qualifying me-too status can be found in EPA’s Pesticide Registration Manual, available as part of the pesticide registration application kit. [35] FIFRA § 3(c)(3)(B); 7 U.S.C. 136a(3)(c)(B). [36] 40 C.F.R. § 152.44. [37] 40 C.F.R. § 152.46. PR Notice 98-10 provides specific examples of labeling changes and product chemistry changes that may be accomplished by notification. [38] FIFRA § 3(c)(9)(C); 7 U.S.C. 136a(c)(9)(C). [39] PR Notice 98-10 provides the text of an acceptable certification statement. [40] Label changes that may be made without notifying EPA are enumerated in PR Notice 98-10. [41] 40 C.F.R. Part 180. Subpart B provides information on procedures for filing petitions. Subpart C provides specific tolerances. [42] 40 C.F.R. Part 180, Subpart D. [43] General information on food additives is at 21 C.F.R. Part 170. [44] FDA’s procedural regulations on food additive petitions are at 21 C.F.R. Part 171. [45] FDA regulations on indirect and secondary direct food additives are found at 21 C.F.R. Parts 173, 174, 175, 176, 177, and 178. [45a] Food and Drug Administration Modernization Act of 1997 (FDAMA). Pub. L. 105-115. [46] FFDCA § 409(h)(6); 21 U.S.C. 348(h)(6). [47] Food Quality Protection Act of 1996 (FQPA), Pub. L. 104-170 , 1996. [48] Antimicrobial Regulation Technical Corrections Act of 1998 (ARTCA), Pub. L. 105-324 , 1998. [49] FFDCA § 201(q)(1); 21 U.S.C. 321(q)(1). [50] FFDCA § 201(q)(1)(B)(i); 21 U.S.C. 321(q)(1)(B)(i).
References [51] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). [52] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). [53] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). [54] FFDCA § 201(q)(1)(B)(ii); 21 U.S.C. 321(q)(1)(B)(ii). Currently there are no treated articles legally available in US markets that make claims of pesticidal activity. All such articles would be considered to make public health claims, which must be registered as pesticide products and substantiated by product performance data. See, generally, 40 C.F.R. § 152.25(a) and PR Notice 2000-1. No protocols have been developed that would enable a registrant to demonstrate the requisite product performance in support of a registration. [55] FFDCA § 201(q)(1)(B)(i); 21 U.S.C. 321(q)(1)(B)(i). [56] See, for example, the Preliminary Risk Assessment for the active ingredient, 1,4-bis(bromoacetoxy)-2-butene, note [26]. [57] FIFRA § 4; 7 U.S.C. 136a-1. [58] RED documents other than those published in the early 1990s are available on EPA’s website at www.epa.gov/pesticides/ reregistration/status.htm. [58a] FFDCA § 408(q); 21 U.S.C. 346a(q). [59] FIFRA § 3(g); 7 U.S.C. FIFRA 136a(g). [60] 65 FR 24585, April 26, 2000. [61] FIFRA § 3(c)(1)(F)(i); 7 U.S.C. 136a(c)(1)(F)(i). [62] FIFRA § 3(c)(1)(F)(iii); 7 U.S.C. 136(a)(c)(1)(F)(iii). [63] Title 3, Cal. Code of Reg. §§ 6159 and 6172. [64] Title 3, Cal. Code of Reg. § 6170(c). [64a] FIFRA § 10(d)(1); 7 U.S.C. 136h(d)(1). [64b] FIFRA § 10(g)(1); 7 U.S.C. 136h(g)(i). [65] 40 C.F.R. Part 152 Subpart E provides information on the procedures required by EPA in order to ensure that data protection and compensation requirements are met. [66] 40 C.F.R. § 152.86. [67] 40 C.F.R. § 152.90. [67a] 40 C.F.R. § 152.95. [68] FIFRA § 3(c)(1)(F)(iii); 7 U.S.C. 3(c)(1)(F)(iii).
[69] 40 C.F.R. § 152.99(b). [70] 40 C.F.R. § 152.99(a)(1). [71] FIFRA § 3(c)(2)(B)(ii); 7 U.S.C. 136a(c)(2)(B)(ii). [72] FFDCA § 408(i); 21 U.S.C. 346a(i). [73] Inert Ingredients in Pesticide Products; Policy Statement, 52 FR 13305, April 22, 1987. 66 FR 57671, November 16, 2001. [74] FIFRA § 10(d)(1); 7 U.S.C. 136h(d)(1). [75] FIFRA § 3(c)(2)(B)(i); 7 U.S.C. 136a(c)(2)(B)(i). [76] FIFRA § 3(c)(2)(B)(i); 7 U.S.C. 136a(c)(2)(B)(i). [77] FIFRA § 6(a)(2); 7 U.S.C d(a)(2). [78] 40 C.F.R. Part 159 Subpart D, Reporting Requirements for Risk/Benefit Information. [79] PR Notices 98-3, 98-4, and 2000-8. [80] 40 C.F.R. § 159.160. [81] 40 C.F.R. § 159.195. [82] 40 C.F.R. § 159.184 and PR Notices 98-3 and 98-4. [83] 40 C.F.R. Part 159 and PR Notices 98-3 and 98-4. [84] 40 C.F.R. §§ 167.3, 167.85. [85] 40 C.F.R. § 167.85. [86] 40 C.F.R. § 169.2. [87] FIFRA § 17(c); 7 U.S.C. 136o(c). [88] 40 C.F.R. § 168.65. [89] 40 C.F.R. § 168.75. [90] FIFRA § 6(b); 7 U.S.C. 136d(b). [91] 40 C.F.R. Part 164 Subparts A and B. [92] FIFRA § 6(d); 7 U.S.C. 136d(d). [92a] FIFRA § 16; 7 U.S.C. 136n. [93] FIFRA § 6(c); 7 U.S.C. 136d(c). [94] 40 C.F.R. Part 164 Subpart C. [95] FIFRA § 6(c)(4); 7 U.S.C. 136d(c)(4). [96] FIFRA § 12; 7 U.S.C. 136j. This section sets forth unlawful acts, including, in part, sales of unregistered, adulterated, or misbranded pesticides; use in a manner inconsistent with the pesticide’s labeling; falsification of an application for registration or other records; and failure to file required reports. [97] FIFRA § 13(a); 7 U.S.C. 136k(a). [98] FIFRA § 13(b); 7 U.S.C. 136k(b). [99] FIFRA § 14(a); 7 U.S.C. 136l(a). [100] FIFRA § 14(b); 7 U.S.C. 136l(b).
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5
Regulatory Control of Biocides in Other Countries Sara Kirkham and Mel Cooke
5.1
Introduction
The regulation of biocides is very varied in those countries with developed chemical control schemes. Some major markets such as Japan have no specific scheme for biocide regulation, and they are treated as ordinary industrial chemicals. Others countries have rigorous schemes, but applied only to certain biocide use categories such as wood preservatives or public-use disinfectants. In this respect, the world situation mirrors that prevalent in Europe before the European Biocidal Products Directive (BPD) (see Chapter 3). The BPD has been very influential, and several non-European countries are moving towards harmonization with the BPD. The BPD is seen as the most rigorous of the regulatory regimes, so that a supplier of biocides in compliance with the BPD will have few extra data requirements in other jurisdictions. In analogy with the European situation, the Organization for Economic Co-operation and Development strives to harmonize requirements for biocide notification amongst its membership of 30 industrialized nations and beyond. However, such world-wide harmonization is many years away. It is an impossible task to give in detail the requirements for all biocides in all countries. Many countries do not recognize biocides as a separately identifiable group of chemicals, and often there is no legal definition. Biocides, as recognized in the EU, therefore often fall under a mix of legislative schemes intended for industrial chemicals, cosmetics, agricultural pesticides, veterinary products, and pharmaceuticals. Each scheme has its own detailed requirements and is administered by different authorities. Often, there are difficult issues of scope between these different schemes, so that an insect repellent used on skin may be viewed as a cosmetic, a biocide, an industrial chemical, or as a medicine. These details, while important, are too complex for thorough investigation in one chapter. More significantly, the information is difficult to ascertain for most countries, unless one is prepared to apThe Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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proach directly the appropriate authorities, and that they are prepared to engage in dialogue. We have tried to present detail as we think it is most useful, concentrating on the major economic areas (except the EU and USA, covered in other chapters) with the most developed regulatory schemes. For brevity, we have mainly assumed the biocide to be a standard chemical, i.e. not polymeric, or an article, or itself a microorganism, or formed in situ.
5.2
Japan
There is no specific registration system for most biocidal products in Japan. Biocides, such as wood preservatives, and swimming pool disinfectants, are covered by the same legislation as ordinary chemicals, but note that some biocides are subject to control at the local (prefecture) level. In Japan, as with the European scheme, some specific applications, for examples fly sprays, biocides with food-contact applications, or uses with humans or livestock, may be covered by other specific legislative schemes. These borderline issues are beyond the scope of this overview. Japan is an important economic area for export of biocides, and because the chemical legislation is significantly different from notification schemes in Europe and the USA, we will describe the most important regulations in some detail. Chemical control of new chemicals in Japan is complicated because different authorities administer the applicable laws. An experienced local agent may be better able to achieve a supply of chemicals in Japan owing to a greater understanding of the philosophy and practice of the various schemes and authorities, and a greater knowledge of the available exemptions and derogations from notification. The manner and courtesy with which they are approached may also influence the outcome of any interaction within Japanese authorities. Having a pre-consultation with each Japanese regulatory authority can facilitate the notification process, especially if foreign study reports are to be submitted. There are some differences in testing methods and interpretation of the test results, especially in biodegradability and bioaccumulation, although the Japanese test methods are, in principle, based on OECD guidelines.
5.2.1
Chemical Substances Control Law
The Japanese Law Concerning the Examination and Regulation of Manufacture etc., of Chemical Substances came into force on 16 April 1974, and was the first new chemicals notification scheme in the world. The legislation is commonly referred to as the Chemical Substances Control Law (CSCL). Until 2000, the CSCL was jointly adminis-
5.2 Japan
tered by the Ministry of International Trade and Industry (MITI), who dealt with the environmental aspects, and the Ministry of Health and Welfare (MHW). The various Japanese ministries have since had changed responsibilities and names. From 8 January 2001, the new Ministry of the Environment (MoE) has also been involved in assessing notifications. Also MITI has been re-named the Ministry of Economy, Trade and Industry (METI). The MHW has amalgamated with the Ministry of Labor (MoL) to form the Ministry of Health, Labor, and Welfare. To keep the distinction between the CSCL and the parallel workplace scheme (see later), the abbreviation MHW will be applied to the section of this Ministry dealing with the CSCL. The main objective of the CSCL is to protect humans from exposure to hazardous substances, including biocides, via the environment, and in particular via the food chain. The CSCL therefore emphasizes assessment of detrimental health effects caused by persistent, accumulating, and chronically toxic substances. Such chemicals are subject to very stringent regulatory actions. The law also identifies substances that are nonbiodegradable but nonbioaccumulative, which were previously evaluated as safe without a full evaluation of their chronic toxic effects. The CSCL notification scheme is, in principle, a stepwise process (see Figure 5.1), beginning with a biodegradation study, and there is a possibility of having to consult with METI part way through. Also, with CSCL notifications, regulatory decisions regarding the test material description are often relevant. Thus, it can take over two years for notification to be able to import or manufacture a new substance in Japan. In order to save time, the notifier may risk testing the parent substance (and not the environmental degradants) and conduct the biodegradation, bioaccumulation, and screening toxicity studies concurrently.
The Inventory of Existing Substances Notifiable new substances are those chemicals not included in MITI/MHW’s List of Existing Chemical Substances, MITI/MHW’s list of notified new safe chemical substances or MITI/MHW’s list of designated chemical substances. These various inventories are commonly referred to as the MITI List (presumably the term METI List will soon catch on). Although there is a separate inventory for the workplace notification scheme (see Section 5.3), the MITI List is normally searched first because an almost up-to-date English version is available as the Handbook of Existing and New Chemical Substances (the Handbook) [1]. Any substance included in the inventory is not notifiable, and is loosely referred to as an existing substance. Nevertheless, there is an administrative distinction between truly existing substances in commerce in Japan when the scheme came into force (as listed in the white pages of the Handbook) and the notified substances (as listed in the green pages). 5.2.1.1
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5 Regulatory Control of Biocides in Other Countries
Fig. 5.1. Flow scheme for Japanese Chemical Substance Control Law Notification.
Each part of the Handbook is split into sections, based on type of chemical, and there is an index by Chemical Abstract Services (CAS) number. However, there is a practical difficulty in determining that a substance not present by CAS number is genuinely not listed in the inventory. This is because there are many entries, especially for existing substances, which have a very broad descriptions. This means that computer searches
5.2 Japan
using various systems (e.g. CAS and Ariel) can result in false negative results. A chemist can search the handbook by structural class, but for many complex substances it is difficult to give definitive advice whether or not a substance is present on the inventory. Japanese industry take a pragmatic and flexible interpretation of the generic inventory entries. Notified biocidal substances are listed on the inventory after a variable period, which may be several years, during which any competitors have to re-notify. A potential new notifier has no means to establish whether their substance has already been notified but not yet listed, or to find out the identity of a first notifier in order to attempt to share the original data, so that sometimes the same new substance is tested twice. The Handbook is always out of date, but notified substances are gazetted periodically. Hence the only way to be sure a substance has not been notified and placed on the “MITI List” is to check the Japanese-language CD-ROM version of the inventory or the official gazette. Exemptions from Notification The notification requirements of the CSCL do not apply to the following biocide applications, because they are subject to separate Japanese control procedures: direct food additives, food packaging (i.e. indirect food additives), detergents for cleaning food-contact materials, agricultural pesticides, and cosmetics (but see below). Note that other provisions of the CSCL still apply to these products exempt from notification. An example of the Japanese approach to dealing with situations of ambiguous legal basis is with ingredients of cosmetic products. It is clear from the CSCL that a new substance (e.g. a cosmetic preservative) is not notifiable when supplied in Japan only in the final cosmetic product. According to the strict interpretation of the Law, however, a new substance for exclusive use to formulate cosmetic products is notifiable if imported or supplied neat. Nevertheless, until about 1998, it was virtually unknown for import of such cosmetic ingredients to be rejected by Japanese customs on the grounds that a MITI number is needed. This may be because an influential Japanese publication [2] clearly states that cosmetic ingredients are exempt from notification. Note that, independent of any requirements under the CSCL, notification under the Industrial Safety and Health Law (see later) is required if the biocide is used in the workplace in formulating cosmetic products. Furthermore, there is a parallel cosmetic approval scheme to ensure safety of cosmetic ingredients. There is a low-volume exemption (LVE) scheme for new substances manufactured or imported at below one tonne per annum. This upper limit applies to all suppliers combined, and hence, if there is more than one exemption in operation for the same substance, the permitted quantities would have to be shared out. Applications must be made annually. Technical and administrative information and certain non-GLP phy5.2.1.2
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sico-chemical data have to be provided. Note that the Japanese manufacturer or importer must make the LVE application, whereas a non-Japanese exporter can make a standard notification. Standard Notification As mentioned, the CSCL notification scheme is designed to evaluate the potential human hazard from exposure to new chemicals through the environment, and the effects of degradants may need to be considered. Impurities contained at above 1 % in a new chemical substance are regarded as components of a mixture. In principle, each such impurity should be tested separately for notification. One benefit of this approach is that the technical-grade substance is considered to be a mixture of notified/existing substances, and consequently its composition can be varied freely if needed. One option is to use purified substances as the test material. Alternatively, the doses used for the three toxicity screening tests can be corrected to 100 %, for a purity below 99 %. Poorly defined reaction mixtures consisting of isomers and congeners can be tested and notified as the mixture. New substances must be notified three months before manufacture or import. For CSCL notification, the Japanese test methods are based on those of the OECD, although some are more stringent, and the standard EU studies have to be enlarged. Many of the studies have to be reported in a prescribed format with the data interpreted in a specific way. There is mutual acceptance of GLP between the EU Member States and Japan. Consequently, the Japanese regulatory authorities will accept foreign studies. In principle, existing GLP-compliant studies conducted to OECD/EU methods for non-Japanese notifiers are acceptable, but the results have to be suitable for interpretation by the Japanese authorities, which in practice may mean only a positive test result is accepted. The first stage in the testing program is to evaluate the biodegradation potential of the substance. To pass the MITI ready biodegradability test, and hence be classified as a safe chemical substance under the CSCL scheme, virtually complete mineralization is necessary (i.e. the only degradants are carbon dioxide and water). The ready biodegradation test is technically demanding, as a mass balance and characterization of degradants is required, and is often best conducted at an experienced Japanese laboratory. If the substance undergoes partial mineralization in the MITI (I) ready biodegradation test, METI/MoE may require a MITI (II) inherent biodegradation study to be conducted on the parent substance, before deciding what to test further. The authorities require that only safe degradation products be produced, so stable degradants may have to be further tested for bioaccumulation and toxicity. Unless complete mineralization is achieved in the ready biodegradation test, the next stage will be to evaluate the bioaccumulation potential of either the parent substance or its environmental degradants. Before conducting Pow (n-octanol-water parti5.2.1.3
5.2 Japan
tion coefficient) or fish bioaccumulation studies, it is worthwhile considering the alternative of assessing the bioaccumulation potential by analogy to chemically similar compounds which have already been tested, either notified new substances or selected existing substances, evaluated and published by METI. If the tested analogue has log Pow <3 or BCF <100, the new substance does not need to be tested and is considered not to be bioaccumulative. Even if the chemical structures are more dissimilar, METI may agree to a shortened version of the bioaccumulation study. Also, for notification of several closely related new substances, a bioaccumulation study may be needed on just one, and this used as a basis for analogy for the others. For some chemicals analogy may be available, but for most the bioaccumulation potential is assessed by measuring the n-octanol/water partition coefficient (Pow) using the OECD flask-shake method. The Pow is not a suitable indication of bioaccumulation potential for biocide substances that are organometallic, surface-active, or which associate in water. An adjustment of the Pow may be required for substances that dissociate, such as acids and bases. Hence, the pKa and a preliminary hydrolysis test are also required as part of the evaluation. If log Pow <3, the substance can be considered unlikely to bioaccumulate, and further bioaccumulation testing is not needed. For those substances still of concern, a fish bioaccumulation study may be required, perhaps with radiolabeled test material. Two concentrations are used, based on the results of a 48 hour Killifish acute toxicity study. There are no published criteria, but if the bioconcentration factor (BCF) 100, the substance is defined as not bioaccumulative, and if 100
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those required for the EU. The mutagenicity tests are evaluated, along with the repeatdose study, according to unpublished informal criteria to decide if the substance is “designated”. A notification consists of a notice of intended manufacture or import of the new substance in Japanese (the so-called Blue Card or New Chemical Substance Card), which provides the technical data and a summary of the studies, and multiple copies of the study reports. Notifications are reviewed in batches approximately monthly. METI, MoE and MHW separately review the submission on various occasions over a period of about two months. Any questions must be answered within about a week to avoid postponement of the review to the next month’s meeting. The notifier or his representative attend hearings at METI, MoE and MHW to explain the study results. The notifier can obtain an unofficial result of the assessment at the end of the review period, but the official letter of judgement which permits import or manufacture of the new substance is sent only after the mandatory three-month waiting period. High-molecular-weight polymers are subject to a reduced notification process. Class I and II Specified and Designated Substances Class I Specified substances are nonbiodegradable, bioaccumulative and chronically toxic to human health. They correspond to the Persistent Organic Pollutants (POPs), which have become of concern worldwide. The intention of the CSCL is to identify such substances and control them. There are only around a dozen Class I Specified substances. These cannot be imported, manufactured or used without permission from METI. Class II Specified substances are nonbiodegradable and chronically toxic to human health but not bioaccumulative. There are around two dozen such substances. The manufacturer or importer has to notify METI of the planned supply amounts and also to provide guidance and advice to the users on recommendations to avoid environmental pollution. Designated substances are nonbiodegradable and not bioaccumulative but suspected to be hazardous to human health on prolonged exposure. There are almost 200 such substances. Suppliers have to report the quantities imported or manufactured to METI, and also inform the users of the properties of the substance. METI undertake an exposure assessment by estimating the total amount in the environment to reach a decision on whether there is a potential for adverse health effects on humans. If so, the suppliers in principle can be requested to provide long-term toxicity tests to decide if the substance will be re-classified as safe or as Class II Specified. In practice this further testing is rarely required. 5.2.1.4
5.2 Japan
5.2.2
The Ministry of Health, Labor, and Welfare Industrial Safety and Health Law
The Industrial Safety and Health Law (ISHL) applies to chemicals used in the workplace, and hence those in domestic use are not covered. It applies to substances manufactured or used in the workplace (either neat or as a component of a mixture). The ISHL supplements the CSCL, is independent, and must be complied with separately. The Ministry of Labor (MoL) administers the ISHL. Since 2000, MoL have been part of the Ministry of Health, Labor and Welfare (MHW), but to facilitate the distinction between the ISHL and the CSCL, the abbreviation MoL will be used. The ISHL scheme came into operation on 30 June 1979. Substances already in use in Japan when the ISHL came into operation, and those notified to MoL since and added to the published list, are not notifiable. Hence notifiable “new” substances are those not included in the MoL’s List of Existing Chemical Substances, MITI/ MHW’s List of Existing Chemical Substances, MITI/MHW’s new chemical substances listed before 29 June 1979 or a new substance subsequently published as notified to MoL. Note that this separate “MoL inventory” is not available in English, and in practice the MITI List is normally consulted first, since this is a good indication that the substance has also been notified under the ISHL scheme and will probably be on the MoL List. There are no exemptions from notification for cosmetic ingredients (e.g. preservatives), and all site-limited intermediates are covered by the scheme since they are present in the workplace. There is a LVE scheme to exempt substances from notification. A workplace user can request an exemption for use of up to 100 kg per annum per factory (i.e. the same company can have several exemptions, one for each site). The application can be made at any time, but must be 30 days before use, and it has to be renewed annually. Only technical and administrative information and non-GLP physico-chemical data have to be provided. The main concern for MoL notification is to evaluate potential on mutagenicity and carcinogenicity. To judge these hazards the MoL require first an Ames test. If the Ames test is negative, or positive under 1000 revertants mg–1, notification normally proceeds without further requests (see Figure 5.2). However, if the results are near or above 1000 revertants mg–1, an in vitro chromosome aberration test is needed. If this second test is negative, there is a good chance that no further testing will be needed. If the second in vitro mutagenicity test is positive, however, MoL will require special actions. For example manufacturers may be asked to inform their employees of the possible risk, and importers or distributors will be asked to use adequate labeling. Also, the MoL may require further tests. If these are also positive, there will be stringent regulation of production and distribution.
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Fig. 5.2. Japanese Industrial Safety and Health Law Notification flow scheme
Once notified, the new substance is allocated a MoL registration number (which is different from the MITI registration number) and it can be imported, manufactured, or handled. A committee of experts reporting to the MoL decides the appropriate protection measures for the workforce based on the substance’s potential for mutagenicity and carcinogenicity effects. There are reduced requirements for polymers, although in practice an applicant may choose to simply perform the Ames test.
5.2 Japan
5.2.3
Hazard Communication
Japanese labeling requirements are not as comprehensive as in the EU and the USA. Specified and designated chemical substances under the CSCL scheme should be labeled appropriately, as should dangerous substances under the ISHL and other legislation. The voluntary MSDS system encouraged for all hazardous chemicals has been extended to become, in effect, obligatory for certain chemicals and businesses from 1 January 2001. The 1999 Japanese Law number 86 Concerning Reporting, etc. of Releases to the Environment of Specific Chemical Substances and Promoting Improvements in their Management makes provisions for introducing this MSDS system to promote the management of substances by industry. This is linked with the Pollutants Release and Transfer Register (PRTR), to be discussed later. The MSDS/PRTR Law covers Class I and II Designated Chemical Substances. These are different to the Class I and II Specified and Designated Substances under the CSCL. Class I Designated Substances in the MSDS/PRTR scheme are substances which may be hazardous to health and/or impair the life and growth of flora and fauna, or which may transform to degradants with these properties, or which may damage the ozone layer. Class II Designated Substances are also anticipated to be persistent and widely distributed in the environment. The MSDS scheme applies to both Class I and II Designated Substances and to products containing them. The chemical substances and businesses to be covered by this PRTR/MSDS system are given in the March 2000 Enforcement Ordinance number 86. The content of the MSDS is officially specified in the METI Ordinance number 401 Pertaining to MSDS of 22 December 2000. The MSDS format is consistent with the international format of ISO 11014. Most of the text has to be in Japanese.
5.2.4
Other Chemical Legislation
The CSCL and ISHL are of primary concern to non-Japanese manufacturers who export chemicals to Japan, but the Poisonous and Deleterious Materials Control Law may be pertinent to biocides: The purposes of this Law is to control acutely hazardous chemicals. The substances classified by this law are listed in publications of MHW. The criteria for classification are:
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* * * * * *
Acute Toxicity Poisonous substance Oral LD50 30 Dermal LD50 100 Inhalation LC50 200 Skin and mucous membrane irritation; Experience by accidents; Other information.
Deleterious substance 300 1000 2000;
For production, import, and sales of these substances, a special license and labeling are required. Labels must give the product name, poisonous ingredient and quantity, name of antidote (in special cases), and company name. Transport of these substances in quantities above one tonne must be accompanied by special instruction manuals for emergencies. The PRTR requires registration and publication of the volume of particular harmful substances released into the environment and the volume of such substances transferred as components of waste. The PRTR is intended to: * * * *
promote voluntary management of chemicals provide basic information for environmental preservation inform the public gauge effectiveness of environmental preservation policies.
The first reports based on the PRTR system will identify the volume of pollutants released by individual businesses in the one year period beginning April 2001. The reports will be submitted after April 2002. The March 2000 Ordinance listed the chemical substances and businesses to be covered by this system. The PRTR system will operate as follows. *
*
*
*
Businesses determine the volumes of release and transfer of Class I Designated Chemical Substances. METI, MoE, and industry jointly aggregate and publish the submitted data for each substance by type of business and by geographical region. As a supplement to the reports received on the volumes of chemical substances released, MoE and METI jointly publish the estimated volumes released by households, agriculture, and other sources. Businesses are to abide by the Chemical Management Guidelines and aim to improve and strengthen their management of chemical substances.
5.3 Korea
5.2.5
Summary
The philosophical basis of the Japanese notification schemes is fundamentally different to the rest of the world. There is also a drastic difference in culture between the Japanese and exporters from Europe and, perhaps especially, North America. These two factors mean that Japanese registration can be particularly difficult. Typically, the first stage in a project is to establish whether a substance is notifiable or not. Since there are two notification schemes, one firstly must establish if either or both apply. The MoL ISHL scheme covers substances, which are manufactured in Japan or used in the workplace. The METI/MoE/MHW (formerly MITI/MHW) CSCL scheme applies to substances manufactured in Japan or imported. There are various blanket exemptions to both schemes. The next stage is to check each of the inventories to identify if a substance has previously been notified or is an existing substance.
5.3
Korea 5.3.1
The Toxic Chemicals Control Law and Ministry of Environment
There is no specific registration system for most biocidal products in Korea. Most biocides, e.g. general disinfectants and wood preservatives are covered by the same legislation as ordinary chemicals. In Korea, some specific applications, for example, biocides for aquarium use are controlled under Animal Health Product Act. These borderline issues are beyond the scope of this overview, and specialist advice should be sought. The general chemical law will be described for this important economic area, as it is applicable to most biocides. The Toxic Chemicals Control Law (TCCL) [3] has been in force since 8 February 1991. The Ministry of Environment (MoE) is responsible for overall environmental preservation, but the administration of the notification scheme has been delegated to the National Institute of Environmental Research (NIER). The NIER conduct a toxicity assessment of the substance before allowing it to be imported or manufactured and decides if any preventative measures are necessary. Existing chemical substances can also be re-evaluated. “A Guide for Chemical Manufacturers/Importers (II) [4]” is available in English for the TCCL. The MoE scheme has been amended, to modify the data requirements for the simplified notification scheme and introduce a GLP system.
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The TCCL applies to all chemical substances, including biocides, except those regulated by other legislation, for example pharmaceuticals, cosmetics (including preservatives), plant protection products (such as biocides added to soil, seeds, etc., this type of biocides is regulated under the Agricultural Chemicals Management Law), direct and indirect food additives, and animal feed additives. However, naturally occurring substances and articles in solid finished form for use by consumers are excluded from the provisions of the TCCL. For manufactured or imported substances, there are also the following exemptions from the TCCL: (i) low volume exemption (LVE, below 100 kg per annum), (ii) small packages of chemical reagents, or (iii) research and development. The manufacturer or importer requesting an exemption must make an application to the MoE at least three days before first import or manufacture. Existing chemicals are also exempt from notification. Existing substances are those manufactured or imported before 2 February 1991 and listed on the Korean Existing Chemicals Inventory (KECI). Substances in commerce in Korea before this date, but which were not nominated for the KECI, can be supplied in Korea without notification on application for exemption to the Korean Chemical Management Association (KCMA). The KECI lists ca. 35000 substances, divided into six categories by chemical structure, with indexes of Korean-language chemical names and CAS numbers. A computer on-line and CD-ROM version of the inventory has been developed by CAS. Also, the KCMA has published a master inventory of ca. 36000 existing substances to consolidate the MoE and MoL inventories. Notification Requirements A new biocide chemical has to be notified to the MoE before it is first manufactured or 5.3.1.1
imported at 100 kg per annum or above. The review period is 45 to 60 days, which is extendable to three months. The form “Notification of Manufacture/Import of Chemical Substances” has to be completed in Korean, ideally with Korean-language attachments. An independent agent can act as notifier, and for foreign importers it is normal practice for a Korean representative to submit the notification. Technical and commercial information is included in the notification, including details of the proposed use and disposal. The results of tests for physico-chemical properties are required, such as melting and boiling point, density, vapor pressure, water solubility, Pow, explosivity, and flammability. The studies required for the toxicity examination are an acute toxicity study in the rat or mouse, using the most appropriate exposure route, Ames test, in vitro chromosome aberration test and ready biodegradability test. If either of the in vitro mutagenicity tests is positive, an in vivo study such as the mouse micronucleus test is needed to confirm the mutagenic potential. Data on abiotic degradation by hydrolysis or photolysis can be included as supporting information. The MoE can request additional studies necessary for the toxicity examination. Compliance with GLP is mandatory. OECD guidelines, Japanese MITI or US EPA methods are accep-
5.3 Korea
table, and an abstract in Korean using the recommended summary form has to be included for all foreign studies. There are simplified notification requirements for biocides that have been established as safe by prolonged use in developed countries. This criterion is met if the substance is in two foreign inventories published before 2 February 1991 with equivalent chemical legislation, i.e. EINECS, TSCA Inventory, the Canadian DSL and NDSL, and the appropriate versions of the Australian and Japanese inventories. If so, either a ready biodegradation test or an acute toxicity study plus an Ames test (or another mutagenicity study), plus the melting point, boiling point, solubility in water or organic solvents, vapor pressure and Pow are needed. Separate notification requirements apply for polymers. The NIER use the information in the notification for the toxicity examination of the new biocide to determine whether it is potentially harmful to human health or the environment, or whether it requires special handling precautions. If the substance has a high probability of causing harm, the MoE may restrict its use, require annual reporting of the amount supplied, or designate it as a Toxic Chemical or an Observational Chemical. The use of a substance is likely to be restricted if the acute oral LD50 is less than 30 mgkg-1, and the notification is not likely to be approved if it is less than 15 mgkg-1. A substance may be considered to be hazardous to the environment either if it is not readily biodegradable and persistent, or if it is toxic and bioaccumulative. The result of the NIER toxicity examination is reported to the notifier and also published in the Official Gazette on an ad hoc basis along with the chemical name and CAS number. Notified new substances do not have to be notified by other suppliers. However, they are not published in a separate inventory, but only in the Gazette, so a prospective new notifier may submit an enquiry to the MoE to establish whether the substance has previously been notified. Toxic Chemicals are substances designated by a Prime Minister’s Decree of the TCCL as being harmful to public health or the environment. They are included in the KECI, and are exempt from notification. Specific Toxic Chemicals may be banned or have their use restricted. As a result of the toxicity examination of notified New Chemicals and the re-evaluation of Existing Chemicals, additional substances will be designated as Toxic Chemicals or Observational Chemicals. There are currently 520 Toxic Chemicals (which includes at least 59 Banned or Restricted Toxic Chemicals) and eight Observational Chemicals, either listed as single chemical substances or in chemical classes (e.g. compounds and salts) in the KECI. Examples of restricted biocides include trialkyltin hydroxide and its salts (use for wood preservatives is banned), and arsenic pentoxide and mixtures containing 0.1 % or more of it are only permitted for additives for goods manufactured in factories. Importers of Toxic Chemicals have to register them annually using the form Application for Item Registration of Toxic Chemicals to be Imported. A fee of is payable, and the
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review period is 5 days. Administrative and commercial information is included in the registration, together with an environmental control plan, which includes analytical methods necessary for such control of certain product types (e.g. insecticides). The MSDS from the foreign manufacturer of imported substances can be used to confirm that the technical information submitted to the MoE is correct. There is a 100 kg per annum low-volume exception from annual reporting of Toxic Chemicals, but none for Observational Chemicals. Any organization engaged in the manufacture, import, sale, storage, transport, or use above a specified amount of Toxic Chemicals has to be registered as a Toxic Chemical Business. The MoE can order such a business to be relocated if there is considered to be a high risk to local residents from accidents involving Toxic Chemicals. Data submitted to the MoE for notification of a new chemical can be claimed as confidential business information (CBI) for three years. The KECI entry would then be a generic name without a CAS number. However, the chemical name can be claimed as confidential only if the substance is not listed in any foreign inventory. The protection of CBI can be extended in three year periods by submitting the appropriate form within 30 days of expiration of the current confidentiality protection. The manufacturer of a substance or a formulated product can, if desired, keep its composition secret from the Korean importer and obtain the necessary customs clearance. This is achieved by providing a Certificate of Composition (COC) giving the product name and listing the components by chemical name. The secrecy of a formulated product can be further ensured by choosing to submit the identity of the components of up to three formulations. The applicant submits the COC to the KCMA to obtain a Confirmation Certificate (CC), which is issued within three days. The CC enables the product to pass customs. It is normally valid for one year, and then is renewable. Chemical substances imported at below 100 kg per annum under a low-volume exemption also require a CC, but this is valid only for a single shipment to ensure the import limit is not exceeded. Note a CC is not needed if the total amount of product imported is below 100 kg. Under Korean custom clearance practice, not all chemical products being imported require product registration at the KCMA for custom clearance purposes. The Korean Customs System has adopted the so-called “Minimal Checking System of Importation Requirements for Chemical Products”, under which the chemical products are classified into two categories: one requiring prior verification of the satisfaction of importation requirements and one for which such verification is not required. In the case of chemical products which fall within the latter category, customs clearance procedures may be completed without any prior review at the KCMA.
5.3 Korea
5.3.2
Ministry of Labor Toxicity Examination
There is also a notification scheme in operation in Korea under the Industrial Safety and Health Law (ISHL) for all substances used in the workplace (i.e. there is no exemption for pharmaceutical substances etc). Consumer products are not covered by the ISHL. Under the interagency program, the NIER review the toxicity of notified new substances and send the report to the Ministry of Labor (MoL). The MoL accept the same studies as MoE. Existing chemicals are those in use in Korea before 30 June 1991, and these qualify for inclusion in the MoL Existing Chemicals List (see earlier). New chemicals are defined as those not on the inventory and, except for chemical elements, natural substances and radioactive chemicals, they are notifiable. The chemical name and degree of toxicity is published in the Official Gazette or a daily newspaper. Reported new chemicals are added to the MoL inventory. However, the applicant can request the notified chemical is listed only by Trade Name for three years, which can be extended by a further three years on request. The chemical name can only be claimed as confidential if the substance is not listed in any foreign inventory or any public document, such as a CAS entry. The MoL can exempt new chemicals from toxicity examination on the grounds that they are nonhazardous or there is no risk of worker exposure. New chemicals are also exempt if they are only for research and development, used by consumers without being processed by industry in Korea or if supplied at below 100 kg per annum. The MoL have introduced a material safety data sheet (MSDS) scheme, in the EC/US 16-heading format. The MSDS has to be in Korean. An MSDS must be provided when a hazardous chemical substance or mixture is sold or supplied, and Korean manufacturers and importers must ensure they are available during transport, storage and use of the chemical. Hazardous substances are defined as those classified according to the criteria of Annex 1 of the MoL Notice. The physico-chemical properties and health criteria correspond with those of the EU, except for the specific health effects of carcinogenicity, mutagenicity, and toxicity for reproduction. Substances are classified as dangerous for the environment broadly according to the EC criteria. Hazardous preparations are mixtures which contain any hazardous substance at 1 % (or 0.1 % for a carcinogenic substance, as designated by the American Conference of Governmental Industrial Hygienists). Korean-language labeling is obligatory, although English labeling according to the UN/IMDG code is adequate to allow import and transport to the first destination in Korea, but Korean labeling then applies for storage. The full chemical name can be kept secret in the MSDS and product label. In general the classification and labeling criteria are similar to the EU, although in particular with differences for environmental classification.
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Like other developing nations, the environmental laws in Korea are developing rapidly to move more into line with international standards.
5.4
China 5.4.1
Biocide Products for Pest Control (BPPC)
The regulations for biocide products in China encompass all avicides, piscicides, repellents, and attractants used for pest control in agriculture, rodenticides, molluscicides, insecticides, and acaricides. The biocidal products must be registered with the Institute for the Control of Agrochemicals, Ministry of Agriculture (ICAMA), before importation. The registration consists of three stages (see Table 5.1). Tab. 5.1.
The three stages of registration Duration
ICAMA Examination Time
Field trial stage
1 year
3 months
Temporary registration stage
1 year
3 months
Formal registration stage
12 months
The biocidal product may not be imported or sold during the field trial stage. ICAMA may then determine that a trial period is required, and may grant a registration certificate valid for one year. The applicant can market the product in limited quantities and areas specified by ICAMA. Thereafter, the applicant must apply for a formal registration certificate. The certificate is valid for five years and allows the applicant to market the BPPC without restriction. Any change of formulation, content, composition, range of use, or method of use must be reported to ICAMA. The registration certificates may be extended. 5.4.2
Disinfectants and General Biocidal Products (DGBP)
DGBPs will be allowed to be imported, sold, and used in China only after getting Approval Certificates from the Ministry of Health. The foreign manufacturers of DGBP may apply for approval certificates themselves or through agents. The application and approval process comprises four stages: inspection stage, acceptance stage, evaluation stage, and approval stage. The applicant first applies for product inspection with organizations designated by the Ministry of Health to obtain an inspection report, and then an Approval Certificate.
5.4 China
There is no statutory time limit for the issuance of such certificates. The Ministry of Health holds a quarterly meeting to evaluate the applications received before the end of the second month of each quarter. The validity period of approval certificates varies from case by case, normally three years for disinfectants, and may be extended. The Ministry of Health also approves preservatives for food or feedstocks for nonagricultural use, and embalming and taxidermist fluids. Biocide products other than those mentioned above are regulated as industrial chemicals according to the Regulations for Environmental Management on the First Import of Chemicals and the Import and Export of Toxic Chemicals (EMFIC). EMFIC requires foreign exporters to register all chemicals before first introduction to the Chinese market, either neat or as a component of a mixture. Chemicals are reported to State Environmental Protection Agency (SEPA) using the form Application Form for Registration of Environmental Management on the First Import of Chemicals completed preferably in Chinese, although there are English instructions for completion, and SEPA may accept the form in English. The review period is up to 180 days. Pesticides are also covered by these Regulations, but are registered with the Ministry of Agriculture, who exchange registration data with SEPA. The administrative, technical, and commercial information required corresponds to that for notification of a new substance in the EU under the Seventh Amendment (Council Directive 92/32/EEC). The suggested physico-chemical, toxicology, and ecotoxicology studies, including their annual and cumulative tonnage trigger values, are the same as in the EU scheme for reduced and full notification with subsequent Level 1 and 2 testing. Study reports can be in English. The study methods are specified by SEPA, based on OECD Guidelines. Additionally the notification status in other countries is required, together with the proposed labeling, and, if requested by SEPA, a sample of at least 250 g. In practice, a summary of the available studies from an existing SDS is usually adequate, but whatever extra data considered necessary for adequate assessment of the chemical can be requested up to the maximum suggested EU requirements. If the submission is acceptable, SEPA issue a pink Registration Certificate valid for five years. This is renewable on application six months before it expires. If the full mandatory data-set is not available, SEPA can issue a white-colored temporary Registration Certificate valid for one year (extended to two years in justified cases) to enable the missing data to be generated. This registration scheme does not apply to Chinese manufacturers, and hence in effect introduces a nontariff trade barrier in contravention of the World Trade Organization agreement. However, once the proposed Law for the Control of Environmental Pollution on Chemical Substances is promulgated, which covers notification of new substances, existing chemicals, and classification and labeling, domestic and foreign suppliers will in principle be on an equal footing.
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Currently all chemicals should in principle be registered, even those first imported into the PRC before 1 May 1994 when these Regulations came into force. However, an inventory of existing chemicals is being developed, with a view to exempting existing substances from registration. The first edition of the Inventory of Existing Chemical Substances in China (IECSC) of 1995 lists ca. 20000 substances. Chemical substances in registered products will also be included in the inventory. The inventory will be supplemented annually. If there is more than one exporter of a chemical, each would have to apply for a registration, and there are no arrangements for data-sharing or joint registrations. SEPA and the other Chinese authorities involved are required to maintain secrecy, and applicants can make confidential business information (CBI) claims providing they can be justified. However, certain data items are excluded from CBI claims, and these broadly correspond to those excluded under the EC scheme. Classification, packaging, labeling, and transport of imported and exported chemicals have to be in accordance with the United Nations or national requirements for transport of dangerous commodities. Suppliers of chemicals are responsible for labeling and must provide a safety data sheet (SDS).
5.5
Philippines
There is no specific legislation for biocides, and they are thus regulated as ordinary industrial chemicals according to the 1990 Toxic Substances and Hazardous Wastes Control Act (TSHWCA), which covers import, manufacture, processing, handling, storage, transport, sale, distribution, use, and disposal of chemical substances and mixtures. However, chemicals controlled by other Philippine legislation, such as radiochemicals, pesticides, agricultural and veterinary products, pharmaceuticals, and food additives, are not covered by TSHWCA. The Act is administered by the Department of Environment and Natural Resources (DENR), using DENR Administrative Order No.29 which outlines the implementing rules and regulations. A version of the Philippine Inventory of Chemicals and Chemical Substances (PICCS) of ca. 24000 existing chemical substances was published in April 1996, and supplements are available from the Environmental Management Bureau website [5]. The PICCS will be updated every five years. The notification scheme began operating fully only in 1999, and any new chemical (i.e. not on PICCS) is notifiable between 90 days and 180 days before it is imported, manufactured, used, stored, transported, or processed. Notifications take some time for review, so DENR and industry have reached a voluntary agreement to operate an Interim Status Permit (ISP) Scheme, to allow safe use of a new substance while the notification is being evaluated. The ISP is valid for one year, and can be renewed 90 days before expiry.
5.5 Philippines
Standard forms are used for notification, and the submission must be in English. The data requirements include identification, use, supply level, occupational exposure limits, anticipated supply level, use, physico-chemical properties, toxicological properties (including an evaluation of the carcinogenic, mutagenic, and teratogenic potential), and ecotoxicology studies. Abbreviated Information Requirements apply for new chemicals already used in an industrialized country without restrictions imposed on them, and no further testing is needed. GLP-compliant studies are required, conducted to OECD guidelines, or other standard methods and reported in English. Technical dossiers are considered to be public documents, but the notifier can claim certain information as confidential, providing this request is justified. Notarized copies of the notification documents are required. An appointed agent in the Philippines, the importer, or the manufacturer can make the submission. Within 90 days (extendable to 180 days) of receipt of a notification, the DENR Review Committee conduct an assessment to confirm the information provided is adequate and make recommendations for control measures, published as DENR Assessment Reports. Available foreign risk assessments may be used as a basis for this DENR review. DENR can add the new chemical to the PICCS (after a five year waiting period), request further data essential for adequate risk assessment, or issue a Chemical Control Order (CCO) to control those substances that pose an unreasonable risk. CCOs are published in the Official Gazette or other national newspaper. Furthermore, DENR may designate a particular use as a significant new use, and require a separate notification for that use. The applicant must submit a notice of Commencing Import or Manufacture and may request a listing in the nonpublic section of the PICCS. A new chemical is listed on the PICCS five after years of being first notified. In the meantime, repeat notifications are required by subsequent suppliers, and DENR can refer to the original data only with permission from the first notifier. DENR should be consulted for the detailed requirements for exemption from full notification for substances manufactured or imported at below one tonne per annum. Notified new chemicals may qualify for the Priority Chemicals List (PCL) if they are persistent, potentially bioaccumulative, toxic, teratogenic, or carcinogenic. Manufacturers, distributors, users and importers of chemicals on the PCL must obtain a DENR ID number for hazardous wastes disposal and report to DENR on quantities and use.
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5.6
Australia
5.6.1
NICNAS
The majority of biocidal substances are covered by the chemicals notification process under the National Industrial Chemicals Notification and Assessment Scheme (NICNAS). NICNAS is administered within the Chemicals Assessment Division (CAD) of the National Occupational Health and Safety Commission (NOHSC). A comprehensive guide, the Handbook for Notifiers, is available [6]. NICNAS aims to protect people and the environment from the harmful effects of industrial chemicals. New industrial chemicals have to be notified before manufacture or import. The NOHSC perform assessments for the primary toxicology and for occupational health and safety. The Department of Arts, Sport, the Environment, Tourism, and Territories undertakes the environmental hazard assessment, and the Department of Community Services and Health carries out the public health assessment. NICNAS applies to manufacturers and importers of new and selected existing industrial chemicals. The Australian Inventory of Chemical Substances (AICS) lists existing industrial chemicals, which do not require notification. AICS consists of a confidential section and a nonconfidential section. Both sections of AICS give the chemical name, molecular formula, and CAS number, but do not list the notifier. A potential notifier can request the NOHSC to search the confidential section of AICS, providing he can establish a bona fide intent to manufacture or import the substance. Notified new substances are added to AICS after five years, although they can be kept to the confidential section of AICS for periods of five years thereafter, for which a fee is payable for each period. Most commercial biocides, if not on the AICS, will be subject to notification, except for agricultural chemicals, food additives, animal feed additives, and veterinary and pharmaceutical products, which are controlled under separate legislation. Examples of biocides covered by other schemes are given later. Also note that NICNAS does not apply to preparations, but to the components of preparations. New chemicals supplied at below 10 kg pa that do not pose an unreasonable risk are exempt from notification, although suppliers are requested to inform the NOHSC. Note that this exemption for cosmetic ingredients must be approved before supply, and the exemption does not apply to cosmetic preservatives or other ingredients prohibited or restricted in the EU. Also if the ingredient will be present in the formulated cosmetic product at 1 % or more, the supplier must have information to indicate the product is safe. The information required for a full notification essentially corresponds to the OECD minimum pre-marketing set of data (MPD), and is detailed in Parts A, B, and C of the
5.6 Australia
Schedule to the Act. The latest notification fee is A$ 11700, although there is a 15 % rebate if an acceptable draft assessment report is provided. The fee is paid in two portions under the “Submit Once-Review Once” new procedure. The first A$ 500 is paid on submission, and the remainder of the fee is due within seven days of confirmation from the NOHSC that the notification documents are complete. The review period is 90 days, but there is now an Early Introduction Permit option to allow a nonhazardous new chemical to be supplied while the notification is being reviewed. If successful, the applicant is granted an assessment certificate. The studies should be conducted to OECD Guidelines, but equivalent methods are accepted. Tests must be performed in compliance with GLP. Further information may be required when the substance is supplied at 10, 100, 1000, or 10000 tonnes annually, or before the 90 day assessment period begins if this is essential for adequate evaluation of the hazard of the substance. NICNAS provides for confidentiality and flexibility of data requirements. For example, it may be agreed that certain matters required in a notification are irrelevant, unnecessary, or economically prohibitive for the assessment of the chemical. The NOHSC is working towards approval of foreign notification schemes to simplify a subsequent NICNAS notification, and there is a pilot program with the UK and Germany. However, no foreign schemes have yet been approved. The notifier of a chemical listed in a recognized foreign inventory can in principle use the data flexibility provisions of NICNAS on the grounds that certain items of hazard information are readily available. Also, applicants for a standard notification are allowed to submit English-language (or authorized translations) of post-1994 assessment reports from UK or German notifications (Option 1) or from an OECD country (Option 2), together with full background documentation, which will result in fees reduction of up to 40%. Limited notification is available for biocides supplied at less than one tonne per annum (small volume), site-limited chemicals up to ten tonnes per annum and substances used only for research and development for supply at 50 kg to one tonne per annum. The review period is again 90 days, but can be reduced by requesting an Early Introduction Permit for nonhazardous substances. The information required for a limited notification is Parts A and B of the Schedule: identity, physico-chemical properties, amount, use, and potential hazards, including a material safety data sheet (MSDS) and labeling. Application for a permit can be made under the Low Volume Chemicals Category for chemicals that will be introduced in quantities of 100 kg or less per year. This is not a limit per applicant but an Australia-wide limit. The data package consists of identity, information on use, occupational safety, environmental impact, public health, a safety data sheet and a label. The NOHSC will evaluate the application within 20 days, and the permit is valid for three years and is renewable.
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For each notification, the NOHSC prepare an assessment report, a public report (i.e. a nonconfidential version of the assessment report), and the summary report (for subsequent publication in the Chemical Gazette). The assessment certificate is given to the applicant within seven days of publication of the assessment report. Road and rail transport of chemicals in Australia is covered by the Australian Dangerous Goods Code (ADG Code), which corresponds with the United Nations transportation recommendations. The criteria used for classification and labeling in Australia closely parallel those of the EC, except for corrosives and physico-chemical hazards which are in accordance with the ADG Code. However, there is as yet no classification of “dangerous for the environment”. There are National Codes of Practice for classification and labeling of workplace hazardous substances and the preparation of Material Safety Data Sheets [7]. 5.6.2
Biocides Not Covered by NICNAS
The other major legislation covering biocides is the Agricultural and Veterinary Chemicals Act of 1994. Agricultural chemical products by definition includes any substance or organism used to: * * * *
destroy, stupefy, repel, inhibit feeding of, or prevent pests on plants or other things destroy a plant or modify its physiology modify the effect of another agricultural chemical product attract a pest for the purpose of destroying it.
Although this encompasses mainly plant protection products, it has also been deemed to include dairy disinfectants for on-farm use, insect repellents for use on humans, swimming pool disinfectants, and algaecides. Some pest traps and barriers using chemical attractants also require registration. The National Registration Authority (NRA) assesses and registers agricultural and veterinary chemical products and approves the active ingredients in the products. Guidelines for applications are published on the web-site [8], but the most up to date advice is found in the Ag Manual which, is obtained either from AusInfo shops (formerly Australian Government Publishing Service) or directly from the NRA. The NRA distinguishes between a pure active ingredient, a technical grade active constituent (TGAC), and a manufacturing concentrate. The TGAC is defined as the commercial grade of the active constituent as it comes from the manufacturing plant. It may contain impurities but not deliberately added nonactive (inert) ingredients. A manufacturing concentrate on the other hand does contain deliberately added nonactive ingredients, such as solvents or stabilizers. For approvals data must be submitted on the TGAC or the manufacturing concentrate.
5.6 Australia
A TGAC approval is required for each manufacturing source and each technical specification of the TGAC. Approvals for additional manufacturing sources and specifications can be obtained after the initial approval has been granted. The extra information required for a new manufacturing source usually consists of a declaration from the manufacturer regarding composition, and manufacturing processes, and a comparison of batch analyses from the new and old plants. For a new TGAC specification, further test data may be requested. Unlike submissions for the EU BPD, an approval for a new TGAC, including the application for poison schedule classification, can be obtained before an application for registration of a new formulated product containing the TGAC is made, although a single application for both the TGAC and the product is preferred. Some TGACs may be exempt from the requirements for approval. The NRA will exempt on a case-by-case basis substances such as commodity chemicals, those that have a simple chemical structure or those that are complex biological products that are difficult to purify or characterize. Each application for a new active constituent or product must contain a submission overview. The overview gives a “birds-eye view” of the submission and therefore contains general information as well as a summary of all the data provided in the submission. The overview should be no more than 100 pages (preferably 15 to 30 pages). Summaries of studies should be kept to half a page and tables should be used to summarize results. In addition, a draft copy of the product label should be included, with an additional two copies attached to the application form itself. The data package consists of chemical information, toxicological data, and environmental data. The chemical information includes a chemical description of the TGAC, an outline of the manufacturing processes and procedures, specification/formulation details for both the TGAC and product, plus analytical methods, and batch and storage stability analysis data. The chemical data is a pre-requisite for the toxicological assessment. Each application should cover acute, short-term, sub-chronic, and long-term toxicity studies, investigations of reproductive and developmental toxicity, genotoxicity, carcinogenicity, and any available human data. A toxicological database, comprising a full bibliography of all studies provided in the application should also be provided. Published materials alone usually do not contain sufficient detail to allow independent scientific assessment (e.g. individual animal data should be provided). In certain cases, such as for commodity chemicals, scientific argument based on accepted scientific principles or data published in peer reviewed journals may be acceptable. It is possible to submit dossiers prepared under the EU or US schemes, provided they address the Australian Regulatory requirements and are appropriately indexed. The National Occupational Health and Safety Commission (NOHSC) evaluate the toxicological part of the submission. The NOHSC perform a risk assessment using
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data on health hazards of the substance, the potential worker exposure during manufacture and use, and any subsequent exposure. This evaluates the impact on the health and safety of workers who are handling or using the substance, or are exposed to the residues. Applicants are encouraged to complete their own risk assessment which will then be evaluated by NOHSC. Human data is used in preference to animal test data when both are available. Environment Australia is the environment program of the Commonwealth Department of Environment. It undertakes environmental hazard assessments for new agricultural chemical products (or variations to products) on behalf of the Australian and New Zealand Environment and Conservation Council (ANZECC). Environment Australia assesses the hazard to the environment by using information in the application, and also from other sources, such as literature searches and reports from the US Environmental Protection Agency (EPA). From the outcome of the assessment, Environment Australia has the power to request further environmental data, or to recommend specific use restrictions or other label instructions and warnings. It is possible to submit environmental dossiers submitted to the EU or US authorities, but they must be reworked to the Australian format and hazard calculations must be revised to meet specific Australian conditions. Data relevant to the likely environmental exposure of the chemical should be submitted. The applicant needs to determine the relevant areas and provide appropriate data or justify its omission.
5.6.3
Conclusion
Most biocides in Australia will be classed as ordinary industrial chemicals and require notification under NICNAS. Certain product types will be subject to the more stringent requirements of the Agricultural and Veterinary Chemicals Act.
5.7
New Zealand 5.7.1
Toxic Substances Act and the HSNO Act
The full implementation of the HSNO Act 1996 was originally scheduled for 1 April 1999, but came fully into force on 2 July 2001, and allowed the chemicals scheme to begin operating. The HSNO Regulations were implemented from 1 July 1998 for biologicals, i.e. new organisms, and are still under development for chemicals. Final Proposals “Methodology for the Consideration of Applications for Hazardous Substances
5.7 New Zealand
and New Organisms” were made available for public comment, and some of the Supporting Documents for the Methodology (SDM) are also available on the ERMA Website [9]. The existing measures continue in force until the HSNO Act is applied to chemicals. In particular the Toxic Substances Act (TSA) remains operational. Products covered by TSA registrations benefit from the transitional period of the HSNO (three years, extendible to five years), so suppliers of new products are advised to notify under the existing TSA scheme to qualify for transitional status. Biocide substances covered by the TSA include: disinfectants, sanitizers, preservatives, and microbiocides for waste disposal and strip mine sites The 1979 Toxic Substances Act (TSA) and the 1983 Toxic Substances Regulations require new toxic substances to be notified to the Ministry of Health (MoH) before manufacture or import. The information required is only the name, composition and uses, although more can be requested. The MoH maintains a registry of ca. 150000 notified toxic substances (NOTS) by product name and component substances. The definition of toxic in the Act is broad and in practice virtually all substances and preparations are notifiable. The Resource Management Act consolidates over 50 existing statutes governing air, land, and water resources. Included are laws on coastal issues, town and country planning, mining, pollution, water, and soil management. One of the key aspects of this Act was the provision for the establishment of an Environmental Risk Management Authority (ERMA) for the management and control of hazardous substances and new organisms. Hazardous substances are all materials (solid, liquid or gas) which are toxic, corrosive, explosive, radioactive, flammable, oxidizing, or otherwise have the potential to damage human, plant or animal health, or have an adverse effect on the environment. Dangerous goods, explosives, scheduled toxic substances, registered pesticides, licensed animal remedies, and notified toxic substances are currently being prepared for transfer into the framework of the HSNO Act by ERMA New Zealand’s Transfer of Substances Group. This Group has the demanding tasks of identifying substances approved under previous legislation, assessing their hazardous properties and assigning controls, and transferring the NOTS over to the new HSNO regime. On commencement of the hazardous substances part of the Act, all substances that are lawfully used at that time will remain legal, and the controls on them will remain unchanged, even though the legislation they were originally approved under will have been repealed. These provisions will remain in place during the transitional period until the substances are actually transferred, by Regulation, to the main part of the HSNO Act. These substances are being identified through consultation and are currently being assessed against each of the six HSNO hazardous properties: explosiveness, flammability, oxidizing capacity, corrosiveness, toxicity, and ecotoxicity. Regis-
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tered pesticides and licensed animal remedies are expected to be transferred to the HSNO Act in early 2002. Single-component scheduled toxic substances are also undergoing hazard assessment, with a view to transfer in late 2001. Any importer or manufacturer would be advised to notify under the TSA before the substance is transferred to the HSNO Act to ensure its continued supply. The supplier will also be asked for information necessary for Transfer. In effect the new HSNO scheme is a product registration scheme for chemicals, whether substances or formulated preparations. There will be a registry of evaluated products, and any product not listed must be registered. There will be no inventory of existing substances. Nonhazardous chemicals, laboratory research, and development chemicals, chemicals imported only for re-export, and articles are all exempt from reporting. Note that products regulated under separate New Zealand legislation must also be registered under the HSNO Scheme. It is unclear how the hazardous properties of formulated preparations will be assessed. The scheme will be administered by the Ministry for the Environment (MfE) and ERMA. Approval by ERMA will take about 80 days, and fees are payable, depending on the amount of work undertaken by ERMA. The evaluation is complex, and involves extensive consultation of all stakeholders. Risks relative to seven statutory categories have to be considered, and for any risks that cannot be controlled, a detailed cost-benefit evaluation is necessary. The 1992 Health and Safety in Employment Act administered by the MoH, requires that safety data sheets are made available in a specified 4 or 12 section format, although the standard ISO 16-section format is acceptable in practice.
5.7.2
Arrangements for Biocides Classified as Pesticides
Although the Pesticides Act 1979 and the Toxic Substances Act 1979 is being superseded as the HSNO Act comes into force, the Pesticides Board and the Toxic Substances Board shall continue to exist and act during the transition period. Any pesticide, which was a registered pesticide under Part III of the Pesticides Act 1979, may still be imported, sold under the same terms and conditions as would have applied if the Pesticides Act 1979 had not been repealed. If the registration of any pesticide under the Pesticides Act 1979 was subjected to restricted use then the provisions of section 24 (1) of the Act shall continue to apply to the use of that pesticide. The following regulations apply to pesticides: * * *
The Pesticides Regulations 1983 The Pesticides (Antifouling Paints) Order 1989 The Pesticides (Bacterial and Fungal Preparations) Order 1984
5.8 Canada * *
*
The Pesticides (Organotin Antifouling Paints) Regulations 1993 The Pesticides (Organochlorine) Notice 1984 shall apply, with the necessary modifications, to the pesticides described in that notice The Pesticides (Vertebrate Pest Control) Regulations 1983 shall apply, with the necessary modifications, to any controlled pesticide. Controlled pesticides include: sodium fluoroacetate, methyl naphthyl fluoroacetamide, arsenic trioxide, phosphorus, strychnine, and sodium, potassium and calcium cyanide, 3-chlorop-toluidine hydrochloride, alphachloralose (as an avicide), and 3,4-aminopyridine.
Product types covered by the pesticide regulations include wood preservatives and structural treatments, products for use in vertebrate and invertebrate pest control (rodenticides, avicides, and piscides), repellents, insecticides, molluscicides, and acaricides for direct use on clothes. As with other jurisdictions, biocides legislation borders many other assessment schemes. Some examples are: * *
Medicines Act 1981 (insecticides/acaracides for direct use on humans) Animal Remedies Act 1967 (insecticides/acaracides for direct use on pets).
Biocides covered by all Acts except Toxic Substances have formal data requirements on a tiered assessment process like plant protection products. Efficacy is required for all biocides that go through the approval process. Data is used to determine Good Agricultural Practice i.e. effective control without excessive use. For biocides requiring approval, there are extra labels, over those required for biocides controlled as industrial chemicals, for environmental and consumer safety. Environmental assessments are tiered, and when basic data indicate significant environmental exposure additional data relating to route of exposure is required. This can involve field trials.
5.8
Canada
Canada regulates biocides in a similar way to the USA (Chapter 4). Biocides in Canada are regulated by several agencies depending on the particular use category. The UseSite Categories of the Pest Management Regulatory Agency (PMRA) contain many biocidal uses (16 out of 33), including aquaculture, empty food storage areas, industrial process fluids, wood, and swimming pools. The categories do not correspond directly with the 23 product types given in the EU BPD. A comparison of the OECD and Canadian categories is given in Table 5.2.
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5 Regulatory Control of Biocides in Other Countries Tab. 5.2.
Cross reference to OECD product/use typesa
OECD Product Type
PMRA USC No
Canadian Reference/Agency
Public health disinfectants and sanitizers
Bureau of Pharmaceutical Assessment, Health Canada
Personal health care disinfectants
Bureau of Pharmaceutical Assessment, Health Canada
Nonpublic health (private), Disinfectants/sanitizers/bacteriostats
Bureau of Pharmaceutical Assessment, Health Canada
Veterinary area and domestic disinfection
Bureau of Veterinary Drugs, Health Canada
Food/feed area disinfectants
Bureau of Veterinary Drugs, Health Canada
Drinking water disinfectants
Environmental Health Directorate, Health Canada
In-can preservatives
18
Material/PMRA, Health Canada
Industrial microbiocides/slimicides
17
Industrial Process Fluids/PMRA, Health Canada
Material preservatives
18
Material/PMRA, Health Canada
Film preservatives
18
Material/PMRA, Health Canada
Underwater paints/treatments and antifoulants
1 2 22
Aquaculture/PMRA, Health Canada Aquatic Nonfood sites/PMRA, Health Canada Underwater structures and materials/PMRA, Health Canada
Wood preservatives
23
Wood/PMRA, Health Canada
Structural pesticides
21
Structures and surrounding soil/PMRA Health Canada
Sewage disposal areas
17
Industrial process fluids/PMRA, Health Canada
Refuse/solid waste sites
16
Industrial and domestic vegetation control for nonfood sites, Health Canada
Control of microbes in strip mine acid
16
Industrial and domestic vegetation control for nonfood sites, Health Canada
Swimming pools
29
Swimming pools/PMRA, Health Canada
Hot baths
29
Swimming pools/PMRA, Health Canada
Spas
29
Swimming pools/PMRA, Health Canada
Ornamental ponds
29
Swimming pools/PMRA, Health Canada
Rodenticides
3
Empty food storage areas/PMRA, Health Canada Structural/PMRA, Health Canada Various outdoor sites/PMRA, Health Canada
20 32
a Italics denote OECD product type does not relate directly to PMRA USC category. USC given is closest to OECD product type/use category.
5.8 Canada Tab. 5.2.
Cross reference to OECD product/use typesa (Cont.)
OECD Product Type
PMRA USC No
Canadian Reference/Agency
Avicides
32
Various outdoor sites/PMRA, Health Canada
Piscicides
2
Aquatic Nonfood sites/PMRA, Health Canada
Repellents (vertebrate)
31
Various indoor and outdoor sites/PMRA, Health Canada
Insecticides: Insecticides (indoor) Insecticides (outdoor residence) Insecticides (outdoor expanses)
20 26 25
Structural/PMRA, Health Canada Human skin/PMRA, Health Canada Human habitat and recreational areas/PMRA, Health Canada Ornamental outdoor/PMRA, Health Canada Residential outdoor/PMRA, Health Canada
27 33 Molluscides
2 22
Aquatic Nonfood sites/PMRA, Health Canada Underwater structures and materials/PMRA, Health Canada
Other vertebrates
32
Various outdoor sites/PMRA, Health Canada
a Italics denote OECD product type does not relate directly to PMRA USC category. USC given is closest to OECD product type/use category.
5.8.1
Food and Drugs Act
Most disinfectants (including laundry additives and air sanitizers) require approval of both the active ingredient and the formulation under the Food and Drugs Act (FDA). Drinking water disinfectants are covered by the Drinking Water Materials Safety Act administered by Health Protection Branch, Health Canada, and whose data requirements specified in NSF Standard 60). From 14th September 2001 the Canadian Environmental Protection Act (CEPA) notification Scheme will apply to FDA regulated products. The Scheme is discussed in Section 5.8.3. This is an interim arrangement until the proposed Environmental Assessment Regulations (EAR) are agreed which will cover FDA products. Biocidal formulations regulated under FDA need a pre-market application. The active ingredient as such is neither approved nor registered, but its evaluation is considered as part of the formulation. Each formulation is evaluated individually, and supporting data may be required to address the end-use formulation. Provisions exist for cross-referencing information from a formulation already approved. Full registration lasts up to five years, but temporary approval is sometimes granted for up to one year. Approvals can be refused if either safety or product performance cannot be demonstrated or supported by scientific evidence.
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5.8.2
Pest Control Products Act
For preservatives, microbiocides, anti-fouling products, wood preservatives, structural treatments, and products for use in vertebrate and invertebrate pest control, both the active ingredient and biocidal product require approval under Pest Control Products Act (PCPA) administered by the PMRA. General sanitizers (but not those associated with disinfectant claims) are covered by PCPA, but they are reviewed and approved by the board covering biocides for the FDA. For biocides covered by the PCPA, all formulations must contain a registered active ingredient. The registration of an active ingredient is source specific, so that each manufacturer requires a different registration, but applicants can share or read-across the data. The PMRA prefer that an application to register a new active ingredient is accompanied by an application for the formulation, and they can give the specific data required to assess safety and efficacy only if they know the end use. Full registration is for up to five years, and temporary for up to one year. The Occupational Exposure Assessment Section (OEAS) of PMRA requires data for individuals handling formulations, and in some cases to assess incidences of secondary exposure, e.g. in swimming pools. Two guidance documents for environmental assessment are available under PCPA [10].
5.8.3
Canadian Environmental Protection Act
The Canadian Environmental Protection Act (CEPA) is a safety net that covers all substances that are not be subject to assessment under another federal legislation. Embalming fluids are regulated neither as pesticides by PMRA nor as drugs under FDA, and are possibly regulated as workplace substances or commercial chemicals or under CEPA (see later). CEPA covers only a few biocides in use in Canada. The primary focus of CEPA is the aquatic environment, and regard for exposure to the general public. The revised Canadian Environmental Protection Act (CEPA) came into effect on 31 March 2000. CEPA requires new chemical substances to be notified before manufacture or import. Only single ingredients require notification, as formulations are not within the scope of CEPA. Guidance is available [11]. New chemical substances are all those not on the Domestic Substances List (DSL), which is a list of substances in commerce in Canada at 100 kg per annum and above from 1 January 1984 to 31 December 1986. If a new substance is on the Nondomestic Substances List (NDSL), the information required for the notification is considerably less than for a standard notification. The NDSL, which is the 1985 US Toxic Substances Control Act (TSCA) Inventory (as amended) minus the substances on the DSL, attempts to take account
5.9 Switzerland
of established substances which did not happen to be sold in Canada during the period for inclusion in the DSL. The DSL and NDSL contain confidential sections, which can be searched by Environment Canada if a bona fide intent to manufacture or import is established by submitting specified data. The information required for notification of new substances depends on the amount of substance to be imported, and is listed in Schedules to the Regulations. Notified substances are listed in the DSL. After listing they can be manufactured or imported by other suppliers for unrestricted use. Hence substances notified with a reduced data set, because of limited use or exposure or with data waivers, are not listed on the DSL. Also, substances suspected of being “toxic” can only be listed on the DSL after they are regulated under CEPA to ensure their safe use. The Workplace Hazardous Materials Information System (WHMIS), which was established in 1988, aims to protect workers using chemicals by improved communication of hazards. This involves labeling and Material Safety Data Sheets, in English and French, and employee information and training programs.
5.9
Switzerland
In Switzerland, biocides are regulated as chemicals. In time, the control of biocides in Switzerland will fall into line with that of the EU. Currently, there are two important laws controlling chemical substances in Switzerland. The first concerns human health and is administered by the Federal Office of Public Health (Bundesamt fu¨r Gesundheitswesen, BAG). The 1983 Order relating to Toxic Substances (OTS) gives requirements for classification, labeling, listing, and sale of “toxic” substances and preparations for public and commercial use. These substances are listed in the Toxic Substances Lists 1 to 3 (Giftliste), and are updated annually. Chemical substances are classified in terms of toxicity (including CMR effects), and other available data such as human exposure. Substances are placed in one of five classes (Giftklasse) ranging from Category 1 (most hazardous) to Category 5 (least hazardous). The Swiss manufacturer or importer must register all chemical substances that require classification, and preparations containing them, with the BAG. The registration application must include composition, appearance, intended uses, any test results required for classification and product literature. Standard reporting forms are available. It takes about six months for BAG to evaluate the classification of a new substance. The applicant is informed of the classification by BAG, and the decision is first published in the official Amtsblatt, then entered into the Giftliste 1. Products
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containing new substances can normally be registered only when the new substance is listed in Giftliste1, although BAG may make a provisional classification in certain circumstances. An EU-format SDS now has to be provided to all industrial users of dangerous substances. “Toxic” substances can only be marketed by authorized persons who hold the appropriate permit. The second important law is the 1983 Federal Law on Environmental Protection (USG), which deals mainly with the effect of chemicals on the environment and on humans via the environment. The Law is implemented by the Swiss Agency for the Environment, Forests, and Landscape (BUWAL or the SAEFL) through various Ordinances. The 1986 Ordinance on Environmentally Hazardous Substances (OEHS) requires that a supplier can market a substance or formulated product only if he has assessed its impact when handled in accordance with the instructions for use. Environmental classification and labeling in Switzerland has been fully harmonized with the EU. New substances must be notified to BUWAL before they can be supplied or imported in any quantity. Existing substances are defined as ones in EINECS, included in the 1985 Toxic Substances List 1 or marketed in Switzerland between 1975 and 1984 in a total quantity of at least 0.5 tonnes. The authorities can request notification of an existing substance. The categories of substances exempt from notification include pesticides and wood preservatives. The information required for a notification includes the chemical identity, amount manufactured or imported, use, physico-chemical properties, ecotoxicity studies, available mutagenicity studies, and animal toxicity, and recommendations for disposal and labeling. The data requirements for the notification of new substances are based on the OECD recommendations relating to the minimum set of pre-marketing data and are very similar to those in the EC. There are no official reduced data requirements for notification of substances to be supplied only in low amounts, although BUWAL will negotiate on a case-by-case basis for certain of the standard tests to be omitted. There is no official review period, and the new substance can be imported or manufactured by the notifier as soon as BUWAL has received the notification. However, BUWAL can request further information necessary for full environmental assessment of the substance, or take regulatory action at any time after notification. The OEHS requires new fertilizers and soil additives to be registered with the appropriate Swiss authority, and there are declaratory requirements for detergents and washing agents. Also, wood preservatives and plant treatment products can only be supplied when a marketing permit is granted. These current laws will be superseded in the medium term. The Swiss Federal Assembly has agreed the new Federal Chemicals Law on the Protection from Hazardous Substances and Preparations (Chemikaliengetz, ChemG) of 15 December 2000. It is expected to enter into force in 2005, after the implementing Ordinances are de-
5.10 South Africa
veloped. The 1969 Federal Law on Trade in Toxic Substances will be repealed and the 1983 Federal Law on Environmental Protection will be amended. The new ChemG covers packaging, labeling, notification of new substances, and provisions for enforcement. The new law also applies to plant protection products and biocidal products. Harmonization with the EU is anticipated. Hence the existing scheme for plant protection product registration will have to be amended, and a new scheme to cover biocidal products will be developed.
5.10
South Africa
There is no special chemical control scheme for biocides, and they are regulated as industrial chemicals under the Hazardous Substances Act (1973) [12, 13]. The Act is implemented through several regulations. The Act protects human health by the control over their manufacture, use and disposal. Chemicals are classified into two Groups. Group I hazardous chemicals are controlled by a set of regulations which covers their licensing, sale, and disposal. These substances are further subdivided into Category A and Category B chemicals. There are 17 Category A substances, some of which may be relevant to biocidal products, including arsenic and its salts, cyanide substances, and strychnine. Category B consists of 46 substances. These Group I substances cannot be sold without a license. The license is issued by the regional authority identified in the Annexes to the Group I Hazardous Substances Regulations, and is valid until the end of the year of issuance. The South African Bureau of Standards has issued guidance on the classification and labeling of dangerous substances (SABS 0265:1999), which closely resembles European standards, but this is not yet statutory. The risk and safety phrases may be accompanied by pictograms for ease of understanding, although this requirement is not mandatory. Group I, Category A substances labels must include the following information: * * * * *
Chemical name of the product and the hazardous substance it contains The name and address of the supplier The words Act 15 of 1973; Group I Skull and crossbones symbol with the word “Poison” in English and Afrikaans The words Keep Out of the Reach of Children in English and Afrikaans.
Safety data sheets should be in the ISO standard, given in SABS 11014-1. In addition to the Hazardous Substances Act, South Africa operates the Occupational Health and Safety Act, covering worker safety. The Regulations for Hazardous
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Chemical Substances (1995) (No. R. 1179) cover all substances hazardous to health, such as those that are harmful or irritant, and require employees to provide adequate training, medical surveillance, and protective equipment to its employees. Transport regulations are detailed in SABS 0228:1995 and SABS 0229:1996. The South African Bureau of Standards has tried to integrate the South African system of chemical control with that of Europe. SABS 0265:1999 sets out these possible changes, but they are not yet a legal requirement.
5.11
South America
Mexico is working with the EPA and Canada under the North American Free Trade Agreement (NAFTA) to harmonize regulatory practices. The NAFTA Working Group has already developed a harmonized antimicrobial products registration scheme, which covers disinfectants, sanitizers, anti-fouling products, algicides, and slimicides. This scheme has been presented to the OECD Biocides Steering Committee. Nonagricultural pesticides are treated either as a pesticide or chemical. Brazil alone has a pesticide assessment scheme based on risk assessment. The other Latin American countries have fewer resources but follow essentially the same procedures. The focus for these countries is on human health protection. There is increasing pressure to facilitate the registration of generic pesticide products, but there is little infrastructure to stop low quality products being sold.
5.12
India
There are no special requirements for biocides, and their regulation follows that of industrial chemicals. There is a requirement for an MSDS on the substance to be imported, no further information is requested.
5.13
Slovenia
Biocides are covered by Chemicals Act (ZKem) [14], Chapter IV, Placement of Biocides on the Market, which is a notification scheme governed by the Ministry of Health that approximates the EU Directives/regulations on dangerous substances. The Act does not cover preparations that are classed as medicinal products for human or veterinary use, foodstuffs or products which come in to direct contact with foodstuffs and cos-
5.14 Conclusion
metics. A biocide is a chemical, fungi, or micro-organism that has a specific negative effect on harmful organisms. This does not include phytopharmaceutical agents. All other provisions of the Act apply to biocides unless specifically stated otherwise. Active substances may only be put on the market if they fulfill the requirements of the present Act and regulations and if they are included in one of the common lists of the EU or in Annex I, IA, or IB. Before a biocide may be placed on the Slovenian market, the National Chemicals Bureau (referred to as the Bureau) must issue a license for its sale and list the biocide in a register maintained by Bureau. The Bureau issue licenses on the basis of full, shortened, or special procedures. The Bureau determines which procedure is appropriate. The active substance is entered on list I or IA, or on IB if it does not contain a dangerous substance. A shortened registration procedure applies to formulated products containing actives on list I, IA, or IB. A special procedure, where the data requirements are specified by the Ministry of Health on a case-by-case basis, is available for preparations with the same composition (within permitted variance) as a preparation already licensed. In this case, applicant would require a letter-of-access to use the data from the original registrant. The license can be issued for maximum period of ten years. The application for a license should contain information on the notifier, physico-chemical properties, toxicity, ecotoxicity, instructions for use, status of the biocide in the other countries, and classification. There is a 60 day waiting period after submission. The Bureau must either accept the submission, or request more data in this period. The Bureau completes risk assessment for active and preparation, and the license is issued if the biocide can be used safely. Extensions to licenses can be requested. These must be submitted 90 days prior to expiry, and conditions under which the license was issued must remain the same.
5.14
Conclusion
Most of the countries discussed are members of the OECD. The OECD published in 1999 a useful overview of biocide legislation in their member countries [15], and continue to promote increased international co-operation in biocides regulation. Although the Organization is composed of so-called developed countries, developing nations are involved to ensure that OECD policies do not have a negative impact upon nonmember states. Therefore, there is a tendency for nonmember states to abide by OECD decisions. Many countries have approval systems (requiring authorization) rather than notifications (requiring the applicant to supply fixed data requirements) for regulating bio-
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cides. Some countries only regulate certain use types such as wood preservatives, disinfectants, and rodenticides, either through special schemes, or through legislation aimed at other chemical categories such as pesticides or cosmetics. The EU BPD has led towards harmonization within the EU, but there has been a knock-on effect in other countries, such as Switzerland and Central Europe (Macedonia, Slovenia, Poland, Hungary, and the Czech Republic), which have taken steps to harmonize their existing chemicals regulations to the BPD. Some of these central European countries are preparing for future expansion of the EU, while Switzerland aims to reduce trade barriers with the EU. The OECD has aided this effect through the initiation of a biocides program, which takes many of the BPD requirements and integrates them with the US biocides regulations. The OECD program will bring the requirements for biocides in line with those for pesticides and pharmaceuticals, so closing the last big gap in chemical regulation.
References
References
[1] Japan Chemical Daily, Handbook of Existing and New Chemical Substances, Japan Chemical Daily, Tokyo, latest edition. [2] International Trend of Chemical Regulation – A Report Survey into European, American and Asian Countries, edited by the Industrial Hygiene Committee of the Petrochemical Industry Association. [3] TCCL. The scheme was updated by Public Notice Numbers 1994-7, 1994-8, and 199557, which are now in force [4] A Guide for Chemical Manufacturers/ Importers (II) [5] Environmental Management Bureau website: http:\
[email protected]\ [6] Handbook for Notifiers, National Industrial Chemicals Notification and Assessment Scheme, ISBN 0-642-39896-8, www.worksafe.gov.au. [7] National Code of Practice for the Preparation of Material Safety Sata Sheets, www.worksafe.gov.au. [8] Guidelines for Agricultural Chemicals Submissions, December 2000 web publication. www.nra.gov.au
[9] www.ermanz.gov.nz [10] Guidelines for Determining Environmental Chemistry and Fate of Pesticides (T-1-255, Oct 1987) and Suggested Guidelines for Environmental Toxicology Studies. [11] Guidelines for the Notification and Testing of New Substances: Chemicals and Polymers are also now available, together with a website www.ec.gc.ca/substances. [12] A Ortiz, Ariel Research Corporation, in ChemCon 2000, Salzburg International Conference on Chemical Control Regulations, ed. R Feierl. [13] http://www.fnb.co.za/legislation/. [14] Chemicals Act (ZKem), Official Gazette of the Republic of Slovenia (No. 321-09/ 97-2/3). [15] Report on the Survey of OECD Member Countries’ Approaches to the Regulation of Biocides, OECD Environmental Health and Safety Publications, Series on Pesticides No. 9, OECD, 1999.
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Human Health, Safety, and Risk Assessment Roland Solecki
6.1
What Is Risk Assessment?
Biocides are necessary for the control of organisms that are harmful to human or animal health and for the control of organisms that cause damage to natural or manufactured products. However, biocidal products can pose risks to humans in a variety of ways due to their intrinsic properties and associated use patterns. Risk assessment is the determination of potential adverse health effects from exposure to a chemical agent or a mixture of chemicals, including both quantitative and qualitative expressions of risk. A potential health risk of a biocidal product can arise from the active substance and/or further substances of concern added as vehicles, solvents, or additives. Risk in the context of human health is the probability of injury, disease, impairment or death from exposure to chemicals whereas hazard is a potential source of harm. The common methodology for risk assessment can be defined as the combined processes of effects assessment, exposure assessment, and risk characterization, which is the scientific source of the regulatory decision-making process (Figure 6.1). The information gathering forms the basis for the risk assessment process. The core data set and any additionally required information should be sufficient to assess all relevant toxic effects and exposure scenarios. The effects assessment includes hazard identification and assessment of dose-response relationships for all toxicological data submitted for an evaluation of harmful effects posed by active substances and biocidal products, respectively. This process should ascertain all relevant target organs, adverse effects, mode of toxic action, cumulative, and reversible effects as well as the dose-effects relations after the different routes of exposure including the estimation of threshold exposure levels. The hazard will be identified prior to the active substance for direct use in the following assessment of products with that active substance, since there are only limited toxicological data for the biocidal product required. The purpose of hazard identification is to asThe Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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Fig. 6.1.
Common methodology for risk assessment of biocides
certain adverse effects, which are defined as biochemical changes, functional impairments, or pathological lesions that affect the performance of the whole organism or reduce an organism’s ability to respond to additional challenges [1]. This hazard identification procedure should determine whether an agent could cause an increase in the incidence of a particular adverse health effect and whether such an effect is likely to occur in humans. For this purpose, the types and severity of adverse effects, the target organs and tissues, as well as the treatment period must be taken into account. Besides this qualitative assessment, the quantitative relationship should be determined between exposure of investigated individuals and the proportion of subjects demonstrating specific biological changes. This dose-response relationship can be expressed as an observed incidence of toxicologically induced lesions, percent response in groups of individuals, or as the probability of occurrence within a test population. A highest exposure level at which there are no statistically or biologically significant increases in the frequency or severity of any adverse effects between the exposed population and its appropriate control is defined as No-Observed-Adverse-Effect Level (NOAEL). If a
6.1 What Is Risk Assessment?
NOAEL has not been derived, then the outcome of a study might be the determination of the Lowest-Observed-Adverse-Effect Level (LOAEL) at the lowest dosage tested. The first adverse effect that occurs to the most sensitive species is defined as the critical effect [2]. The final step in the effects assessment process is to determine the critical study that contributes most significantly to the critical effect. The exposure assessment is an identification of humans exposed, a description of the composition and size of the population, as well as an evaluation of the type, route, level, frequency, and duration of exposure. It is based on estimated or measured data of biocidal products and closely related to the intended uses of these products. The exposure assessment should cover the proposed normal use of the biocidal product together with realistic worst-case scenarios including reasonably foreseeable misuse. The type of exposure may be primary (i.e. directly related to the application, the person exposed usually knows it) or secondary (i.e. not directly related to the application, the person exposed does frequently not know it). The assessment of primary and secondary exposure for humans is based on the use patterns, application methods and whether the biocide is expected to be applied by professionals or nonprofessionals. In-door applications of biocides have usually a higher impact on human health than outdoor uses for both primary and secondary exposure assessment. The nonfood uses are mostly accompanied with a lower health impact, whereas the potential for direct or indirect food contact is of mostly greater importance for the assessment of secondary exposure. For an aggregate exposure assessment, the impact of cumulative effects from several uses of biocidal products containing the same active substances should take into account [3]. The risk characterization is an estimation of incidence and severity of adverse effects likely to occur in a human population due to an actual or a predicted exposure to any active substances or biocidal products including relevant metabolites and impurities. It is an evaluation of effects data mainly from the active substance and comparison with exposure data of the biocidal product. The comparison of exposure with potential health effects may be done separately for relevant subpopulations, routes of exposure and for critical effects of the agent that contribute to the hazard classification of the product. Benchmark values or Reference Doses (RfD) can be ascertained as a threshold estimation of a daily or interrupted route-specific exposure to the human population that is likely to be without an appreciable risk of deleterious effects during a specified lifetime period. They can be derived from a NOAEL, or LOAEL of the critical study, with adequate safety margins, which shall be obtained in the assessment of the critical effect(s). Such RfD or threshold values can be compared with the predicted or monitored exposure during the intended use of the product for relevant populations to determine the risk as the final step of the risk assessment. The ratio between predicted and acceptable exposure then forms the basis for the decision-making process.
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6.2
Hazard Identification and Assessment
The hazard identification and assessment of the dose response relationship are the two main closely related steps in the effects assessment process to identify quantitative and qualitative aspects of the potential risk of biocides. The hazard identification is an evaluation of the weight of evidence for adverse effects relevant to humans and an ascertainment of any qualitative information that contribute to the assessment of the toxicological profile of a substance. The classification of harmful health effects is based on an assessment of all available data on toxicity and mode of action. The dose-response assessment is an identification of the dosage below a threshold level at which no significant adverse effects are observed. It is based on a characterization of the relationship between the administered dose and the incidence of an adverse health effect.
6.2.1
Information Gathering
The testing of biocidal products and active substances is required by regulations, which are differing between countries. A common core data set forms the basis of the requirements for human health risk assessment. This common core data set is regarded to be a minimum set required for all substances and product types. An additional data set is conditionally required depending on the characteristics of the active substances, the product type as well as the expected exposure of humans, according to its intended main use or application method. The toxicity studies may vary in purpose, design, and conduct ranging from wellstandardized and widely accepted test methods and protocols to basic research oriented investigations employing specialized study designs. Both well standardized and research oriented toxicological studies have been utilized in a broad range of risk assessment paradigms from many investigators, national and international agencies. Although effects assessment for biocides should utilize all relevant and available data acceptable toxicity tests should be in accordance with legally prescribed guidelines. The existence of a great variety of regulations and guidelines, nationally and internationally, has been the motivation for the Organization for Economic Co-operation and Development (OECD) to develop internationally harmonized test guidelines, which have to be applied in all OECD countries after their endorsement. These harmonized guidelines provide the basis to compare studies carried out at different places and to submit the same studies for effects evaluation in different countries, thus providing economic and animal welfare advantages [4]. In addition, all toxicity tests for biocides and other chemicals have to be performed in accordance with Good Laboratory Practice (GLP), which covers an assembly of factors
6.2 Hazard Identification and Assessment
including housing, animal welfare, standardization of laboratory test methods, and record keeping as well as qualification of the test personnel. As a further basic principle for data gathering, the amount of animal testing shall be minimized. This means that all unnecessary testing of biocides should be avoided. In certain cases, a study might be technically not possible to perform and the data should not be generated because of the intrinsic properties of a substance (e.g. very volatile, oxidizing or otherwise reactive substances). In some other cases, it is not scientifically justified to perform an animal study due to the intrinsic properties of the chemical (e.g. the irritative properties of corrosive chemicals shall not be studied in animals). Occasionally, other existing data can be used instead of the required data. Existing data on similar substances may be read across to fulfil the data requirement for another, especially in the case of frame formulations. Some of the core data requirements may be waived on a case-by-case basis due to prerequisites fulfilled on limited exposure and plain toxicity profile. The decision for waiving of core data requirements may be possible on a careful consideration of both the level, frequency, and duration of exposure to the biocidal product and the toxicity profile of an individual active substance [5]. Based on these considerations an expert judgement is necessary to assess whether a common core data is not needed. The acceptable justifications for nonsubmission of data required for effects assessment may be different on a case-by-case basis and depends on the anticipated use. Biocidal products used only in closed industrial systems, apart from the possible contamination of the human environment, have a potential for occupational exposure of a usually low magnitude, which should be considered for adequate testing for that specific aspect. On the other hand, when biocides are expected to reach the food chain or drinking water as contaminants, more comprehensive testing including long-term toxicity is necessary. The human health effects assessment for biocides is generally based on data from biocidal active substances and biocidal products, respectively. The full core data set including studies on metabolism, toxicokinetics, acute oral toxicity, repeated-dose toxicity, genotoxicity, carcinogenicity, reproductive toxicity, and further specific effects is restricted to active substances to avoid unnecessary testing for the great number of biocidal products. For the effects assessment of products, only data on acute toxicity, irritation, and sensitization are required. For comparable or nearly identical biocidal products or frame formulations, transference of data might be possible. An effects assessment for solvents, additives, and other substances in the preparation will be in principle based on the safety data sheets for these components.
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6.2.2
Hazard Identification
The hazard identification is an evaluation of toxicological and metabolism data, which should critically evaluate each study or other available information in detail. Within this standard package there is a wide range of study types investigating numerous end points after different treatment periods. Information for use in the hazard identification is primarily derived from toxicological studies involving animal models. The causal relationships between exposure to a biocide and induced toxic effects can be readily established using such animal studies. However, a major principle of regulatory toxicology requires that these animal data should be relevant to the human setting. The choice of animal species in the respective guidelines has been generally based on a number of factors including husbandry requirements, purchase and maintenance costs, size, lifespan, characterized genetic and developmental history, and knowledge of historical records [6]. Rats are the most commonly used laboratory animals for toxicity testing of biocides. Rodents such as mice, hamsters, and guinea pigs are much less frequently employed and restricted to special endpoints. Some studies are also conducted using dogs and rabbits as a second nonrodent species. Increasing concern about the ethics of animal experimentation has served to catalyze efforts leading to the possible replacement or reduction in the use of animals, and the refinement of test methods to minimize the stress and suffering to animals. Isolated cells, tissues and organs can be prepared and maintained in culture by methods that preserve their in vivo properties and characteristics. In vitro testing contributes to the hazard assessment of biocides particularly for the genotoxicity endpoint, permitting a decision concerning the need for further in vivo testing. Some effort was also reached to develop and recommend alternative in vitro methods for further endpoints (e.g. irritation, corrosivity, sensitization, tumor promotion, and specific mechanistic aspects of organ toxicity). However, the relevance of in vitro data to humans sometimes remains difficult to assess [7]. Although most data required for human health risk assessment will be obtained from animal studies, the evaluation of human data is important since it can supplement findings in animal studies. Such data may include information following accidental or occupational exposure, medical surveillance data on manufacturing plant personnel, epidemiological studies on the general population, and human volunteer studies. The reliability of human data may however be more questionable than data obtained in animal studies. Acute Toxic Effects Acute toxicity is defined as the occurrence of adverse effects within a short time after administration of a single dose of a test substance, or to divided dosages given within 6.2.2.1
6.2 Hazard Identification and Assessment
24 hours. Acute toxicity studies are aimed at identifying dose levels producing death or serious signs of toxicity for the main purpose of classification and labeling. The investigation of clinical signs and pathological effects in these studies can provide first preliminary information on the toxic nature of a substance. However, the currently performed acute toxicity tests are usually not appropriate to determine the NOAEL for critical effects. A comparative hazard assessment of acute adverse effects following exposure on different exposure routes might be possible since biocidal products and active substances shall be administered via three or at least two routes, respectively. The choice of the routes will depend upon the nature of the substance and the likely route of human exposure.
6.2.2.2 Irritation, Corrosivity, and Sensitization
The irritation, corrosivity, and sensitization endpoints should be examined for both biocidal products and their active substances. Testing for skin irritation is performed to evaluate the irritating potential of a substance as a reversible dermal response from acute or repeated exposure. The severity of skin irritation is measured in terms of erythema and oedema and their persistence. The primary eye irritation test is intended to predict the potential for a single splash of a chemical in the eye to cause reversible or permanent damage. The effects assessment for skin and eye irritation involves a hierarchical screening process to avoid testing of severe irritants or corrosives in animals. Thus, a test substance shall not be studied for skin and eye irritation if the active substance is a strong acid or base. For potential corrosive substances or severe skin irritants, the eye irritation test shall not be required. The sensitization tests investigate the potential human hazard to cause skin sensitization reactions likely to arise from repeated dermal exposure potential of a biocide. Once an individual has been sensitized, a symptom may follow any subsequent skin exposures to the allergen. Hypersensitivity shall be determined by a repeated application of a biocidal product or an active substance, given after a sensitizing treatment. While the guinea pig Maximization test is considered to be the preferred adjuvant technique particularly for active substances, there may be good reasons for choosing the Buehler test or the Local Lymph Node Assay (LLNA), especially for biocidal products.
6.2.2.3 Toxicokinetics and Metabolism
Toxicokinetic studies can provide important basic information about oral absorption, distribution, accumulation, metabolism, and excretion of a substance. The tests provide basic data about the rate and extent of oral absorption, the tissue distribution, the routes and rate of excretion, and the main metabolic pathways including relevant me-
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tabolites, particularly in urine and feces. These data are of great value for the estimation of internal exposure levels, identification of target organs, metabolites of toxicological concern, the potential for bioaccumulation, and excretory mechanisms. The relative toxicity of the parent compound and metabolites can be considered together with the speed and effectiveness with which the body clears the substances. A single application with two different doses, and a repeated dose toxicokinetic study is required for the active substances usually in rats by the oral route. Additionally an appropriate dermal absorption assessment is needed for the active substances, which may provide information on the possible route specific toxic behavior or potential for dermal toxicity. Information on dermal absorption for biocidal products should contribute to the estimation of effects of solvents and additives to the dermal absorption of active substances. 6.2.2.4 Repeated Dose Toxicity
Repeated dose toxicity testing provides information on adverse effects as a result of subacute, subchronic or chronic exposure. The effects observed are mostly a mixture of both adverse and adaptive effects since transient effects produced by one or two doses may be corrected by feedback mechanisms and thus not identified by the end of the study. Subacute studies on active substances are mostly performed to identify a dose range, which could be used in the follow-up studies. When such a study is properly planned, the results provide a fair basis for a first toxicological evaluation, which may be appropriate for a short-term risk assessment. Because of the extensive histopathological, clinical chemistry, and hematology examinations performed in subchronic toxicity tests, they provide the most information on the major toxic effects of a test substance and indicate the main target organs affected. Two different species shall be investigated. Usually rat is the preferred rodent species. The dog is often a useful nonrodent animal model for the investigation of specific effects on particular organ systems (e.g. cardiovascular system, gastro-intestinal tract). Subchronic toxicity study in the second animal species might be waived if the subchronic studies in the first species are without any indication of substancerelated adverse effects at the highest suitable dose level, or if the mechanism of the toxicity is known and it is justified that the toxicological effect is not specific to the first species and mechanistic studies can show scientific evidence that the toxicological profile does not differ between the animal species. In a chronic toxicity test, the long-term toxicity profile of a substance can be characterized. The test is required for one rodent and one other mammalian species. Biocidal active substances that are expected to give rise to continuous human exposure or exposures for relative long periods of life should preferably be tested in chronic toxicity tests. The long-term-toxicity of an active substance may not be required where a full
6.2 Hazard Identification and Assessment
justification demonstrates that the subchronic studies in rodents and nonrodents are without indication of substance-related adverse effects at the highest suitable dose level. 6.2.2.5 Genotoxicity
The testing of genotoxicity is a hierarchical screening program to identify substances, which might cause permanent transmissible changes on a single gene, gene segments, or chromosomes. These tests provide pre-screening information on the genotoxic carcinogenic potential of a substance and the possibility of detecting genotoxicity in vitro and/or in vivo. Three in vitro tests (i.e. for gene mutations in bacteria, for clastogenicity in mammalian cells, and for gene mutation in mammalian cells) are always required. When all of the three in vitro tests are negative, there is adequate evidence that the substance has no genotoxic properties. If at least one of the three in vitro tests is positive, then appropriate in vivo genotoxicity testing will be necessary. Such in vivo methods are considered to be more relevant for risk assessment because they demonstrate the potential for genetic toxicity in the presence of toxicokinetic and metabolic processes as well as chromosome repair mechanisms. These additional in vivo tests should be selected on a case-by case basis taking into consideration genetic end-points, mechanistic and cell-specific aspects, toxicokinetic and toxicodynamic properties. 6.2.2.6 Carcinogenicity
The carcinogenicity study, in which rats and mice of both sexes should be used, identifies the carcinogenicity potential of biocidal active substances in laboratory animals in order to facilitate the extrapolation of potential risks to humans. In the cancer bioassay both genotoxic as well as nongenotoxic carcinogens can be detected. The studies must be sufficient to establish the species and organ specificity of tumors with their dose-response relationship. For nongenotoxic carcinogens, these studies should identify the threshold dose for the carcinogenic potential. Additional mechanistic studies shall study possible tumor promoting properties. The carcinogenicity of an active substance may not be required where a full justification demonstrates that these tests are not necessary. Waiving of carcinogenicity studies may be possible if no genotoxic potential for humans is identified in tests of genotoxicity and if possible mechanisms of toxicological effects observed in repeated dose toxicity studies are without any indications of nongenotoxic carcinogenicity, and there are no structural alerts for carcinogenicity.
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6.2.2.7 Reproductive Toxicity
The always required test battery for reproductive toxicity consists of a two-generation reproduction toxicity study in rats and studies for teratogenicity in two species, usually rats and rabbits. The observed adverse effects in two-generation studies on parental toxicity and reproductive performance are related to a repeated feed intake. No other studies can provide comparable information for the effects assessment on male and female fertility, specific sensitivity of neonates and offspring, endocrine effects on reproductive functions, specific sensitivity during the first part of pregnancy and lactation, or transgenerational exposure. Furthermore, these tests may give additional information on any enhancement of general toxic effects in pregnant animals. Teratology studies generally use gavage dosing for approximately 10 to 15 days during gestation. The main aim is to investigate developmental effects on the fetus and maternal-toxic effects on the dam. The major manifestations of developmental toxicity include death of the developing organism, structural anomalies such as malformations or variations, altered growth, and functional deficiency. Any effects on the fetus can be considered as being caused by a single or few doses, but this is usually not justified by standard guideline studies. The parameters investigated for nonreproductive end points in the dams are often very limited and may be influenced by a modified susceptibility in pregnant animals. Teratogenicity studies in the second species might be waived, if no developmental effects are observed in the first species and if no developmental or reproductive effects in the two-generation reproduction toxicity study are observed at the highest suitable dose level. 6.2.2.8 Special Effects
Additional mechanistic studies should be performed to study special effects of a substance or to clarify mechanisms of target effects. Such studies may be necessary when there are indications that active substances may have immunotoxic or hormone related effects or when the mechanisms for nongenotoxic carcinogenicity, developmental toxicity, or species-specific effects need to be investigated. The significance of such specific investigations to man will need to be assessed on a case-by-case basis as there is no standardized design applied for such studies. Therefore, it is difficult to use the NOAEL from such studies for the derivation of any RfD. However, such mechanistic studies are of high importance to modify the selection of safety margins. Various biocides have specific neurotoxic properties, which can include changes in morphological, physiological, behavioral, or biochemical parameters. If there are any indications that the active substance may have neurotoxic properties then specific neurotoxicity studies are required. Indications of neurotoxicity can be acquired from the systemic toxicity studies as adverse effects in the central and peripheral
6.2 Hazard Identification and Assessment
nervous systems. Expert judgement is required to decide whether a specific study is needed to investigate acute, subchronic and/or developmental neurotoxicity. However, an investigation of neurotoxic effects is already possible using repeated dose toxicity tests with incorporation of specific neurotoxicity measures, like sensory activity, grip strength, and motor activity assessment. Additionally, delayed neurotoxicity studies on hens can identify critical neurotoxic effects for specific substance groups (e.g. organophosphates and carbamates). Toxicity testing of degradation products, by-products and reaction products is required only on a case-by-case basis where human exposure is significant. These data may be relevant only for such types of biocides where reaction products or metabolites can be formed that normally not occur in mammalian test systems (e.g. for special residues or harmful substances produced in a reaction with water or on the surface of treated materials). Toxic effects for livestock and pets should only be estimated for biocides that will be used in spaces in which animals are housed, kept or transported or for which exposure to relevant amounts of residues via drinking water or feeding stuffs is possible. 6.2.2.9 Medical and Other Human Data
Medical data in anonymous form are always required for biocides. Information following accidental or occupational exposure, medical surveillance data on manufacturing plant personnel, practical data, and information relevant to the recognition of the symptoms of poisoning, or on the effectiveness of first aid measures can provide valuable data to confirm animal studies and to identify unexpected adverse effects, which are specific to humans. The data may consist of published articles or unpublished medical surveys. It is usually not possible to require these data for new biocides. Epidemiology studies should be considered wherever possible. The quality of these investigations often varies between anecdotal information to full studies conducted to Good Clinical/Laboratory Practice guidelines. They do not usually play a significant role in the effects assessment of biocides. Human volunteer studies can provide uniquely valuable information that serves to reduce substantially the uncertainty of risk assessment. In such studies low doses of biocides are administered over short periods directly to fully informed human volunteers. This may be possible especially for compounds with a well-understood and reversible mechanism of toxicity, which can be monitored by noninvasive techniques or blood sampling and nonradioactive analytics. Such data may be important in biocidal risk assessment and can remove the uncertainty of interspecies extrapolation. However, it is not is not acceptable to expose humans to biocides only for the sake of lowering the assessment factor. The incorporation of such human data in the determination of threshold values may either increase or decrease the value as determined in the
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absence of such data. Ethical considerations should be evaluated careful when designing human studies. The performance of such human studies is only acceptable, if they fulfil the respective national and international ethic conventions.
6.2.3
Dose-Response Assessment
Many of the adverse effects on health caused by biocidal substances are not expressed until the active component reaches a threshold concentration in the relevant tissue or receptor. The purpose of dose-response assessment is therefore to determine any predicted threshold doses, the shape of the dose-response curve and the relationship between administered dosage and severity of an adverse effect, where possible. Because of differences in mechanisms of action and in toxicokinetics, these parameters may vary considerably for different routes of exposure and in different species. The observed threshold dose in a toxicity test will also be influenced by the sensitivity of the measured parameters and endpoints. The incorporation of quantitative data on toxicokinetics and toxicodynamics into dose/concentration-response analyses for effects assessment approaches can lead to the estimation of a presumed safe (i.e. subthreshold) value. It also lends to a presentation of dose-response in a probabilistic context, where data are sufficient to confidently characterize the distributions of interest [8]. For most toxic effects, such as hepatotoxicity, neurotoxicity, reproduction toxicity, irritation and corrosivity, a threshold can be expected. The threshold for the same adverse effect might be different following acute, subacute, subchronic, and chronic exposure in the same test system based on adaptive mechanisms, time related sensitivities, age associated lesions or progressing cytotoxicity. For sensitization, a threshold can be assumed for induction of sensitization, but not for a response in an already sensitized individual. For indirect interactions with the DNA such as the spindle poison activity resulting in the induction of aneuploidy in mitotic and meiotic cells, it is mainly accepted that a threshold concentration may be exist. For mutagenicity and genotoxic carcinogenicity, a threshold exposure level cannot be supposed, even if a dose-response relationship may be shown under experimental conditions. It may be sufficient for such endpoints to evaluate whether the biocide has the inherent capacity to cause such an effect. Thus, a qualitative assessment of the likelihood that an adverse effect will occur can be carried out.
6.3 Exposure Assessment
6.3
Exposure Assessment
Exposure to biocides can occur in markedly different ways in both occupational and domestic settings. Many biocidal products are intended solely for use in the professional or industrial sectors. Other biocidal products are widely available to nonprofessional users as products for private use. The pathways of such consumer exposure also include the potential for biocide residues in manufactured goods, food and drinking water that was preserved against any pests. Such consumer exposures may occur over a long time period or be incidental [9]. It should be expected that exposures to biocides do not occur as single or independent events, rather as a series of sequential or simultaneous events that are linked in time and place. Consequently, the approach of an exposure assessment should focus on the potential exposure from more than one source to a single biocide by multiple routes to individuals in a population. In this way, all temporal (i.e. exposures via all pathways occur in time), spatial (i.e. exposures via all pathways occur in place/location) and demographic (i.e. exposures via all pathways occur in age/gender/ethnicity and other demographic characteristics) relationships for an individual should be considered [3]. Based on these characteristics for one person, a distribution of total exposure to the individuals in a population of interest can be created.
6.3.1
Characteristics of Human Exposure
There is an obvious need for good exposure data. Requirements for data to assess exposures for biocides should be based upon consideration of use patterns, application methods, whether the biocide is expected to be applied by professionals or nonprofessionals, whether its use is indoor or outdoor, whether it has the potential for food/feed contact or not, whether any adverse effects of the biocide are likely to be acute or chronic, and whether sensitive subpopulations might be exposed. Furthermore, human exposure can be characterized by being primary or secondary, by the level, frequency, and duration or by the route of exposure [10]. Primary exposure occurs to a person using biocidal products, and others involved in mixing and loading, application or post-application activities directly related to the application such as cleaning of equipment, maintenance of industrial plants and handling of freshly treated items. Secondary exposure occurs post-application not directly related to the application and includes exposure via environment to bystanders and consumers, who may be have little or no control over this exposure [5]. Examples of populations that can be affected by secondary exposure include the immediate family of a professional user, the consumer, the maintenance engineer, or the work-
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place colleague, who could be unwittingly exposed to biocidal products. The exposure could be also categorized based on thresholds with regard to the relevant level, frequency and duration of exposure. The magnitude and the time are important characteristics, which must be taken into account for the description and assessment of exposure. The magnitude of human exposure is actually determined by the external concentration of a substance in the formulation or in the treated material and the internal dose level, which reached the target in the living organism. The estimation of external exposure is the assessment on how much of a substance contacts the human body that reflects the potential dose of a substance that can be absorbed. For calculation of the internal exposure, toxicokinetic data are required to estimate the disposition of the substance in the body including absorption, distribution, and elimination parameters. Therefore, the external concentrations of the active ingredient together with the toxicokinetic properties are key elements in the exposure assessment. The duration and frequency of the contact with a biocidal product or their residues determines the magnitude of exposure and are closely linked to the specified risk groups. A professional user may be exposed during a considerable part of his life, whereas nonprofessional products could be used only occasionally. Operators, bystanders and other exposed peoples can come into contact with biocidal products by inhalation, dermal contact or by ingestion. Many biocidal active substances have relatively low volatility (i.e. <1 x 10–2 Pa at 20 8C) so that exposure through inhalation will only be likely if a preparation is applied in a manner which generates aerosols, particles, powders or droplets in an inhalable size range (i.e. <50 micrometers). Physical and chemical properties have also a decisive influence on the dermal penetration of molecules. For substances with a high lipid solubility or low molecular weight exposure through skin contact is likely. The nature of carriers and the dilution factor of the substance are also decisive (e.g. nonpolar carriers increase dermal penetration). For substances which molecular weights >500 and log Pow (n-octanol/water partition coefficient) <–1 or >+4, a likely low dermal absorption percentage can be expected. Exposure via ingestion depends on the oral absorption rate, which is estimated in toxicokinetic studies. The amount is difficult to assess but may need to be addressed, if the product routinely comes into contact with unprotected hands of operators or its application is resulting in food residues. 6.3.2
Occupational Exposure
Occupational exposure may include for the same individuals the primary exposure during application of biocidal products and/or secondary post-application exposures on the working place [11]. Exposure during application and post-application for work-
6.3 Exposure Assessment
ers and bystanders can be divided into a number of use scenarios of occupational settings with regard to frequency, magnitude and user groups. Disinfectants in a closed circulation system are removed and refilled once every week or month, whereas spraying of insecticides may occur daily during a prolonged period of the year. If industrial processes are highly automated, there is a very minor chance of exposure to the biocidal product, whereas already partly automated processes can lead to relevant spread of contamination. The magnitude of exposure is far higher where manual processes predominate the working sector. If industrial processes are mainly manual in the handling of biocidal products, they create much more opportunities for contact with applied biocides. The occupational use of biocides involves usually only a restricted part of the whole population not including special subpopulations such as toddlers, children, and the elderly. Exposure of industrial workers include automated applications of extremely diluted products in completely closed industrial systems as well as hand application of highly concentrated products with the use of personal protective equipment (PPE). Decanting, mixing the biocidal product, contact with working solutions, and contact with treated materials may also introduce such a potential for exposure to biocides. If workers, as bystanders, come into contact with biocidal products from treated materials and preparations, they can be unaware of the nature of the biocidal product used, when handling and processing of newly treated material. People who work in food preparation and in clinical environments may be exposed to recently disinfected surfaces where they can contact dislodgeable residues. There are also risks of exposure from operations such as secondary manufacturing, package or quality control work as well as maintenance and cleaning operations. Exposure of nonindustrial professional users is characterized by close contact with the biocidal product, for instance as a pest control operator or commercial painter using anti-fouling products. Products tend to be applied by hand held sprayer, dispersion of powders, dipping, application by brush, or by other manual methods. The working conditions are variable and are affected by many external factors such as changing weather conditions and restricted work areas. Professionals are expected to have legal duties to control exposure. They have access to engineering control measures and knowledge of how and when to use PPE. However, in all cases the work environment and human factors play an important part in determining the ultimate exposure. Storage and handling of products, use of suitable and adequate PPE, ergonomics of the workspace, methods of work, and safe disposal are important factors, which affect exposure. Other factors are training of professional users, understandable information on risks of adverse effects on workers, and supervision in the workplace. Generally, professional users of biocidal products should have correct knowledge in the handling of biocides. They are expected to take realistic precautions using PPE and to ensure high occupational hygiene standards, if necessary.
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Suitable engineering controls and post-registration monitoring should guarantee the correct use of PPE, whenever practical.
6.3.3
Consumer Exposure
Consumer exposure involves a large diversity of products, a great variation in the use of biocidal products and a broad spectrum of consumer behavior including the whole population such as children, elderly, and disabled people. Thus, different toxicity endpoints relevant for specific subpopulations must be anticipated. The exposure scenarios could be constant rather than transient with widely differing time scales. Products could be used occasionally once every few years or used every day for months so that the impact of time needs special consideration in the exposure assessment. This requires an exposure assessment that involves different exposure durations, different toxicity endpoints, and different exposed populations [9]. Biocidal products for nonprofessional use are usually available through the retail trade, especially for the application in home or garden. The range of products varies greatly from ready-prepared baits to liquids that will be sprayed or brushed. The related exposure of nonprofessional users may lead to absorption of large quantities of biocidal products with less control over the magnitude. Indirect exposure of populations via the environment may occur through drinking water, the food chain, the global atmosphere, and residential exposure including reentering treated zones in which exposed groups may be have little knowledge and mostly no control over this exposure. It must be assumed that those people are exposed through their environment without any protection against biocidal active substances. People and their pets are also bystanders following the application of publichygiene pest-control products in the home or in public places or the in-door use of film and wood preservatives. Exposure of private users of treated products includes handling of goods, preparations, or articles, which have been treated with biocidal products to protect them against harmful organisms. Because of the commonly low level of residues the secondary exposures to treated products may be of less immediate concern. However, it will always be necessary to assess the significance of the predicted level of exposure. Nonprofessional users are assumed to have no training in the safe handling of biocidal products and may not accurately understand and follow label instructions, and so assessment of their potential exposure needs to take reasonably foreseeable misuse scenarios into account. They will not usually use PPE so that dermal and inhalation exposure may be considerably greater than for professional users of the same product. Therefore, the exposure assessment should take into consideration the foreseeable exposure from normal product use and the foreseeable misuse such as accidental
6.4 Risk Characterization
ingestion of liquid biocidal product or freshly treated materials. Risks to children following these types of application need careful assessment.
6.4
Risk Characterization
The risk characterization process brings together the assessments of hazard, doseresponse, and exposure to make an estimation of incidence and severity of adverse effects likely to occur in a human population of interest. This integrative analysis should carefully identify which endpoints in a particular risk assessment are most appropriate and which elements most affect the exposure and risk conclusion. The most appropriate endpoint will be compared with the exposure estimate for the most relevant applications. Default assumptions (e.g. absorption rates) must be used at several stages because the necessary database will never be complete. Therefore, the risk characterization should also describe the quality of available data and the degree of confidence to be placed in the risk estimates [6]. It is an appraisal in the light of current scientific and technical knowledge that supports the risk manager in making public health decisions. For this reason, the basic criteria for a risk characterization should be transparency, clarity, consistency, and rationality.
6.4.1
Threshold Exposure Levels
The effects assessment reveals a list of NOAEL and LOAEL for the different types of studies available for the active substances. The first step of the risk characterization process is the selection of the most relevant study with their NOAEL/LOAEL for each type of toxicological endpoint (i.e. subacute, subchronic, chronic, carcinogenicity, reproductive toxicity, and if relevant neurotoxicity). The choice of the most relevant endpoint for the risk characterization will mainly depend on the toxicological profile of an active substance, but may also be influenced by the intended exposure scenarios of the biocidal products with that active substance. Thus, the duration of the study from which the NOAEL for the critical effects is chosen should be appropriate to the main use pattern of the products. For long-term exposure (e.g. from food residues or high impact indoor use), NOAEL should be derived from chronic toxicity/carcinogenicity studies. For single exposures, NOAEL from acute studies would be most appropriate (e.g. acute neurotoxicity studies). However, the data available for the majority of short-term risk characterizations do not contain specific studies, which address the end-points and treatment periods relevant to determine an acute NOAEL accurately.
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A NOAEL from studies with the relevant route of administration should be used where possible. However, most of the studies available will have used the oral route. Since in a lot of dermal studies no systemic adverse effects are observed at the limit dose level of 1000 mg/kg body weight (e.g. based on a very low dermal absorption rate), the value of this route of administration for choosing relevant NOAEL is mainly inadequate. It is recognized that the NOAEL is related primarily to the experimental design. As a consequence, its relationship may be inappropriate to the biological response depending on the quality of the experimental design. A further problem with the current risk characterization approach is that NOAEL used for derivation of reference-dose values are commonly obtained from a single study. While there are often several studies that could be used for a particular critical effect, risk managers will choose one study because it appears to have advantages over the others. As a result of these stumbling blocks, there has been an increasing tendency to move away from the traditional choosing a NOAEL as a point of departure for establishing regulatory benchmarks towards probabilistic risk assessment. The possibility of developing a probabilistic approach to risk characterization has been discussed in several publications [11, 12]. 6.4.2
Safety Margins
Safety margins accounting for uncertainties in the extrapolation from toxicity data to the exposed human population have to be applied for the translation of critical NOAEL into regulatory benchmarks. The term Assessment Factor (AF) is meant as a general term to cover all factors designated in the literature as safety factor, uncertainty factor, or adjustment factor. A number of different AF can be applied to determine regulatory benchmarks. At present risk characterization for noncancer toxic endpoints makes mostly use of standard default AF. These are based on a tenfold factor for interspecies variability and a tenfold factor for intra-individual variability when considering risks to the general population. Indeed, an overall AF of 100 has been applied for a majority of regulatory benchmarks. In order for either toxicokinetic or mechanistic data to contribute quantitatively to risk assessment, the procedure of applying tenfold factors for inter-species differences and human variability was recently refined. It was demonstrated that physiologically based pharmacokinetic modeling may be of value in determining the appropriate factor to use, and that the appropriate use of quantitative toxicokinetic and toxicodynamic data to address interspecies and interindividual differences in dose/concentration-response assessment can improve the scientific basis for the justification of AF [8]. Where the critical NOAEL is based on animal data, a factor of ten is normally applicable. If the critical NOAEL is based on reliable human data, a factor of one may be
6.4 Risk Characterization
suitable. In special cases, where there are data that permit a more reliable comparison of animal versus human sensitivity for the critical toxicological effect of the substance, consideration should be given to refine the standard interspecies factor of ten. Analyzed data on inter-species differences indicated that the tenfold standard interspecies factor could be subdivided with a factor of four (100.6) for toxicokinetics and 2.5 (100.4) for toxicodynamics. The current precautionary approach of applying a tenfold factor for interindividual intraspecies differences should be a first default procedure, unless a convincing scientific case can be made for applying a lower factor. This factor of ten might be divided evenly into two sub-factors each of 100.5 (3.16) for toxicokinetics and toxicodynamics, respectively. Other modifying factors for the selection of the overall AF might be the confidence of the database, the type and severity of the critical effect, uncertainties in the route-toroute extrapolation, and correction of a route specific absorption. When in exceptional cases the most appropriate study does not provide a NOAEL, the lowest dose may be used as a LOAEL, but this situation must be reflected in choosing and justifying the AF. A higher safety margin between the exposure and the overall NOAEL established might be necessary if only a limited set of toxicological studies are available or there are severe effects such as malformations at a very low dose level. Finally, a careful and detailed discussion and weighing of all available data is an important element for the final choice of the overall AF. The basis for the proposed overall AF needs to be clearly stated based on distinct AF for interspecies differences, intraspecies differences and other modifying factors. 6.4.3
Benchmark Concepts
At present, there exist a plethora of potential benchmarks that can be derived from several toxicological studies. They may be performed on different species, different time durations, and for different routes of exposure. Different benchmarks are also possible for specific subpopulations, particularly at different life stages. Since the type of exposure to biocides may be primary or secondary, the development of a flexible concept for different benchmark values referring to groups, which are primary and secondary exposed, is necessary for the feasible exposure scenarios. Thus, the establishment of benchmark values for applicators/operators (i.e. mostly primary exposure), and for consumers (i.e. mostly secondary exposure) should be considered, if necessary. Depending on the characteristics of human exposure, the target tissues, critical effects, and the NOAEL may differ considerably, so that more than one benchmark may be established to allow for flexibility considering the anticipated exposure situations. The selection of most relevant issues should be performed on a case-by-case basis. Although the establishment of regulatory benchmarks is heavily based on expert
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judgement, its derivation needs to be reported as transparently as possible. Any agreed benchmark might need to be reassessed in the light of new data. The benchmarks used in the risk characterization of active substances should be firstly health-based limits or Reference Dose values, since only a limited number of exposure scenarios are available. These RfD will be based on the overall NOAEL of the most relevant endpoint in the most sensitive relevant animal species of the full toxicological package required for biocidal active substances. As a default procedure, three time-related RfD for long-term, intermediate-term, and short-term exposures would be suitable for the oral, dermal, and inhalative route, respectively. However, the multiple sources of potential variability in the derivation of ay RfD can lead to confusion and regulatory inconsistencies. As such, there is a real need for pragmatic simplification and harmonization. From a pragmatic standpoint, there needs to be consolidation of information that will lead to fewer RfD. Lifetime exposures are of importance for the majority of biocidal active substances, which are expected for food contact including drinking water. Such long-term exposures might be also relevant for substances, which are bioaccumulating, continuously applied, or persistent following in-door use. In such cases, a long-term RfD should be derived comparable to the concept of acceptable daily intake (ADI) estimation [13]. Intermediate-term dermal and inhalation exposures are most frequently important in both occupational and residential scenarios. NOAEL from the same medium-term and intermediate term studies used as the basis for consumer RfD might be sufficient for assessing acceptable margins of exposure for occupational applications. For such cases the current concept for the derivation of an internal Acceptable Operator Exposure Level (AOEL) may be applicable [14]. Short-term exposures are sometimes important for single applications by nonprofessional users. In such cases, RfD derived from subchronic or long-term studies are mostly not an appropriate toxicological benchmark for assessing the risk posed by short-term exposure to acutely toxic substances. As a matter of standard practice in the risk assessment of residues in food and drinking water, the case for setting an acute reference dose (ARfD) should be considered [15]. The ARfD of a chemical can be defined as “an estimate of a substance, that can be absorbed over a short period of time (e.g. during one day) without appreciable health risk to exposed peoples on the basis of all known facts at the time of evaluation” [16]. However, the toxicological studies for an estimation of acute NOAEL are very limited in the core data set. In most cases, short-term RfD must be calculated from subacute and intermediateterm NOAEL. Therefore, short-term and intermediate-term RfD might be based on the same critical effects of the same study. The derivation of a minimal number of RfD should be sufficient for the majority of active substances that can be used to estimate acceptable margins of exposure for the different biocidal products based on their specific use scenarios.
6.5 Regulatory Decision-making
A more flexible approach may mainly be used for authorization/registration of biocidal products. This may be realized by an application of Margins of Safety (MOS). For each biocidal product, a MOS can be calculated based on a comparison of the specific exposure data for the product with the most relevant toxicity endpoint derived from the most relevant study. Uncertainties in the exposure estimates and possibilities for exposure reduction (i.e. PPE) may ultimately be taken into account for a final conclusion on the magnitude of the MOS. These estimated MOS for each biocidal product can be compared with the AF. Based on the calculated MOS, the risk manager needs to conclude whether the involved exposure to the substance is of concern or not. If the MOS is greater than the AF, no health risks are anticipated. If the MOS is lower than the AF, the exposure is considered unacceptable.
6.5
Regulatory Decision-making
The decision-making process as the most important part of the risk management must take into account the full risk assessment process including a well-founded comparison of the risks and benefits. The appropriate managerial response to a potential health hazard must be selected for active substances and biocidal products separately. However, the final decision-making cannot be done separately for human health aspects. It is a combination of conclusions for humans, animals, the environment, efficacy, and unacceptable effects on target organisms such as resistance. Based on these conclusions and all results of the risk assessment together with political, social, economic, and engineering implications several management options can be developed. Consequently, the appropriate managerial response in the decisionmaking process depends on the legal ground rules for the risk assessment of biocides including data requirement as well as the political background of the various countries. Therefore, the decision-making process is described for the EU Biocidal Products Directive scheme [1, 17], as a specific example that is currently under discussion, but not yet finalized. However, the general principles apply to regulatory schemes in other OECD countries.
6.5.1
Decisions for Active Substances
The final decisions for active substances may be that biocidal products with that substance can be authorized, registered, or otherwise placed on the market. In these cases, the active may be included in a positive list of allowed, notified, or assessed biocidal active substances. It may be necessary that the decision-making process must be post-
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poned, if not all relevant data are submitted. If it appears that further information is necessary for a full evaluation, the risk management authority shall ask that the applicant submit such information in a specified time period. If all required information is available and acceptable, the decision-making process should compare the results of the full human risk assessment process with the criteria agreed for the inclusion in the positive list. Active substances, which give no rise to concern, can be included in such a positive list. The reason for concern would be mostly the nature of the critical effects (e.g. sensitization, corrosivity, carcinogenicity, mutagenicity, and reproductive toxicity), which cause concern for human health with regard to the use and exposure patterns. The several directives or other regulations specify certain criteria for the placing of active substances in a positive list, which are more or less different in different parts of the world. If the risk is considered to be unacceptable to human health and no safe use can be demonstrated, withdrawal from the market should be considered. Before such a decision can be made, the need for products containing the active substance should be considered. There may be cases, where there is no alternative means of adequate biocidal pest control or health-care reasons, if the active substance were to be withdrawn from the market. This may be of importance especially for pest control agents, if there are only a limited number of active substances to protect human health safely against specific pest organisms possibly based on a high degree of resistance to other actives. If the benefit may take precedence over the risk, it may be necessary to allow a specific minor use of such an active substance, but definitely for a limited period during which alternative means of control should be actively developed. Especially for such active substances, which have shown some concern, a comparative assessment might be necessary [1]. If new active substances are included on the positive list for the same purpose and their use causes significantly less risk to humans at equivalent efficacy, then the entry on to the positive list of such substances may be refused. However, only risks and benefits with regard to human health risk assessment should be compared with each other. A comparison of human health risk with environmental risk will be unfeasible and meaningless. If the comparative assessment leads to a decision to replace a listed active substance, completely or for a specific use area, by a less risky alternative, the substance shall remove from the market in an appropriate time period. 6.5.2
Decisions for Products
The final conclusion will be either that the biocidal product can be authorized/registered or cannot be placed on the market for the use as applied for. In some cases, it will be necessary that more data are required before a decision on authorization or regis-
6.5 Regulatory Decision-making
tration can be made. After submission of additionally required data, the risk assessments shall be re-evaluated and possibly revised in the light of new information on the hazard of the product and/or exposure. The human health risk assessment for biocidal products shall consider all possible effects on the relevant exposed human populations (e.g. professional users, nonprofessional users, and humans exposed via environment) when making a decision on an authorization or registration. If the human health risk assessment has shown in the light of current scientific and technical knowledge, that a biocidal product has no unacceptable effects itself or as a result of its residues, on human or animal health, directly or indirectly (e.g. through drinking water, food or feed, indoor air, or consequences in the place of work) or on surface water and groundwater, the final regulatory decision-making might be that the biocidal product can be authorized or registered for the use as applied for [17]. An unacceptable concern is triggered if the estimated or measured dose exceeds an appropriate RfD or the combination of the highest level at which no toxicological effect is observed and the acceptable MOS. In such cases, it may be necessary to combine an authorization with specific conditions or restrictions. These may include a restriction of use categories (e.g. to professional use only); restriction of specific application methods with high human exposure (e.g. brushing but not spraying); restriction in the field of use (e.g. no indoor use); modifications of formulation (e.g. ready-for-use rather than concentrate); modification of packaging, labeling, and measures for the protection of applicants (e.g. reduced pack size); and/or reduction of the application rate. An authorization can also be combined with special risk management measures to protect human health (e.g. breathing-masks, overalls, gloves, and other PPE) in order to reduce exposure for operators. It may be that these risk reduction measures can remove the risk or reduce it to an acceptable level. A refinement of the exposure assessment can additionally revise a specific risk characterization (e.g. estimates from exposure models may be replaced by specific exposure measurements). In such cases, more data might be necessary before a decision on authorization or registration can be made. However, before deciding that further data should be required, careful thought must be given as to how useful the additional data will be for a realistic refinement of the risk characterization. Any risk management authority shall not authorize a biocidal product if the human health risk assessment confirms that the product presents an unacceptable risk to humans in a foreseeable application. If the relationship between the exposure and the effect cannot be reduced to an acceptable level then no authorization can be given for the biocidal product. Additionally, there may be specific health criteria, which specify conditions under which no registration/authorization for specific use conditions will be possible. Thus in the European Union, no biocidal product classified as toxic, very toxic, or as a category 1 or 2 carcinogen, or as a category 1 or 2 mutagen, or
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classified as toxic for reproduction category 1 or 2, shall be authorized for use by the general public [17]. The decision-making process for biocidal products shall also consider the health risks of a nonuse of such biocidal products, which are necessary to control organisms that are harmful to humans. If a biocidal product cannot be authorized on the basis of an adequate risk measures and realistic exposure estimates, the risk management authority must consider the possible acceptability of the risk in comparison with the benefits of a special application. Such benefits for human health may be to prevent the outbreak and spread of communicable diseases between humans, from animals to humans, and between animals or to prevent microbial spoilage of food and foodstuffs and otherwise protect consumers from contaminated products. The public health benefits of using a particular disinfectant to treat drinking water may far outweigh the risks arising from the disinfectant and also the alternative of using a disinfectant that is less efficacious. Thus, there may be exceptional cases where a high level of human health protection from the use of a biocidal product outweighs the human health risk from its use. The risk management authority must therefore perform a risk-benefit analysis on a case-by-case basis including a transparent risk communication with regard to the advantages and disadvantages to the exposed populations.
6.6
Conclusions
Biocides are necessary for the control of organisms that are harmful to human or animal health and for the control of organisms that cause damage to natural or manufactured products. However, biocidal products can also pose risks to humans in a variety of ways due to their intrinsic properties and associated use patterns. A potential health risk of a biocidal product can arise from exposure to the active substance and further substances added to the biocidal product as formulants. Risk assessment is the determination of potential adverse health effects from exposure to biocides. The information gathering forms the basis for the risk assessment process. The methodology for human health risk assessment can be defined as the combined processes of effects assessment, exposure assessment, and risk characterization, which is the scientific source for a regulatory decision-making process. The effects assessment includes hazard identification and assessment of doseresponse relationships for all toxicological data submitted for an evaluation of harmful effects posed by active substances and biocidal products, respectively. The exposure assessment is an identification of humans exposed, a description of the composition and size of the population, as well as an evaluation of the type, route, level, frequency, and duration of exposure.
References
The risk characterization is an estimation of incidence and severity of adverse effects likely to occur in a human population based on an evaluation of effects data mainly from the active substance and comparison with exposure data of the biocidal product. The ratio between predicted and acceptable exposure then forms the basis for the decision-making process. The decision-making process as the most important part of the risk management must take into account all results of the risk assessment process including a well-founded comparison of the human health risks and public health benefits of a special biocide application. Based on these risk/benefit conclusions and all results of the risk assessment together with political, social, economic, and engineering implications several management options can be developed. The decision-making process should be transparent with regard to the scientific background and the political influences and the risk manager should provide a justification for the conclusion reached to make sure that, when biocidal products are properly used for the purpose intended, they have, in the light of current scientific and technical knowledge, no unacceptable effect on human or animal health.
References
References
[1] Draft for Technical Notes for Guidance in Support of Directive 98/8/EC. Principles and Practical Procedures for the Inclusion of Active Substances in Annexes I, IA, and IB (in preparation), ECB, 2001. [2] Integrated Risk Information System, Glossary for Risk Assessment Terms, EPA, 2000, Available online at http://www.epa.gov/iris. [3] Guidance for Performing Aggregate Exposure and Risk Assessments, EPA 1999, Available online at http://www.epa.gov/ fedrgstr/EPA-PEST/1999/ [4] Principles for Assessment of Risk to Human Health from Exposure to Chemicals. EHC, 210., WHO, Geneva., IPCS, 1999. [5] Technical Guidance Document in Support of the Directive 98/8/EC, Guidance on Data Requirements for Active Substances and Biocidal Products, ECB, 2000, Available online at http://ecb.ei.jrc.it/biocides/. [6] Principles for Assessment of Risks to Human Health from Exposure to Chemical, EHC 210 , WHO, Geneva, IPCS, 1999. [7] Assessing Human Health Risks of Chemicals: Derivation of Guidance Values for Health-Based Exposure Limits, EHC 170. WHO, Geneva. IPCS, 1994.
[8] Guidance Document for the Use of Data in Development of Chemical-Specific Adjustment Factors for Interspecies Difference and Human Variability IPCS 2001. Available online at http:// www.ipcsharmonize.org/CSAFsummary.htm. [9] Assessment of Human Exposures to Biocides, Report to CEC DG XI from the Biocides Steering Group, ECB, 1998. Available online at http://ecb.ei.jrc.it/ biocides/. [10] Occupational and Consumer Exposure Assessments, Paris, OECD, OECD Environment Monographs No 70 OECD, 1993. [11] P.S. Price, R.E. Keenan, J.C. Swartout, C.A. Gillis, H. Carlson-Lynch, M.L. Dourson, An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty, Risk Anal. 1997, 17, 427 – 437. [12] T. Vermeiere, H. Stevenson, M.N. Pieters, M. Rennen, W. Slob, B.C. Hakkert, Assessment Factors for Human Health Risk Assessment: A Discussion Paper, Crit. Rev. Toxicol. 1999, 29, 439 – 490.
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6 Human Health, Safety, and Risk Assessment [13] Draft Guidance for Setting of an Acceptable Operator Exposure Level (AOEL). Doc. 7541/VI/95 rev 5., dd. 03/01/2001 (in preparation), EU, 2001. [14] Guidelines for Predicting Dietary Intakes of Pesticide Residues, WHO, Geneva, WHO, 1989. [15] Pesticide Residues in Food-1997, Report of the JMPR, FAO Plant Production and Protection Paper 145, FAO Rome, FAO/ WHO, 1997.
[16] Pesticide Residues in Food-2000, Report of the JMPR, FAO Plant Production and Protection Paper, FAO Geneva, FAO/ WHO, 2000. [17] Draft for Technical Notes for Guidance in Support of Annex VI of Directive 98/EC. Common Principles and Practical Procedures for the Authorization and Registration of Products. (in preparation), ECB, 2001.
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Environmental Safety and Risk Assessment Robert Diderich
7.1
What Is Risk Assessment? 7.1.1
Introduction
Over the last 15 years, environmental risk assessment has found its way into regulatory decision-making regarding the marketing of chemical substances. Specifically for biocides, a survey conducted by the Pesticide Program of the Organization for Economic Co-operation and Development (OECD) in 1997-98 [1] shows that most OECD member countries have notification or approval systems in place for at least some biocidal use categories. For example, in the European Union, 23 use categories have been defined in the biocidal products directive (EU-BPD [2]) for which approval is necessary before a biocidal product can be put on the market. In the USA, a large number of biocidal use categories are regulated under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) or the Federal Food, Drug, and Cosmetics Act (FFDCA). Regulatory procedures between countries appear to be similar. While risk assessment is performed for human health in all regulatory schemes for biocides, environmental risk assessment is less systematically performed. In the following sections and chapters, a brief overview of the environmental risk assessment procedure is outlined. The methodology as it is currently being developed for decision-making under the EU-BPD is described to illustrate general principles. The main aspects of environmental risk assessment will be addressed, estimation of releases of biocidal substances into the environment, transport mechanisms, and degradation behavior within different environmental compartments as well as adverse effects upon aquatic and terrestrial organisms. The decision scheme based on the risk assessment as well as on other considerations is briefly described.
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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7.1.2
Definitions and Process
The EU biocidal products directive [2] requires that a biocidal product can only be authorized if it “has no unacceptable effect itself, or as a result of its residues, on the environment”. This means that under the prescribed use of the product, the amount of the product which is released to the environment must not have any adverse effects upon the ecosystems which constitute the environment. The process, by which the potential adverse effects upon the environment due to the use of a chemical substance are estimated is called risk assessment. In more technical terms, the environmental risk assessment of chemical substances can be defined as the process comprising the following steps: hazard identification, effects assessment, exposure assessment, and risk characterization [3, 4]. According to Annex VI of the EU BPD, the definitions listed in Table 7.1 apply to each step of the risk assessment process. Ecological hazards include lethal effects, such as fish or bird kills and sub-lethal effects on growth and reproduction of various populations. For the effects assessment, data are obtained from laboratory studies with plants or animals or from experimental field studies with plants or animals. Exposure assessment can be assessed by measuring exposure concentrations once chemical substances are used and emitted. For new chemical substances, or proposed new uses of existing substances, exposure assessments are predictions. In order to be complete, the risk assessment is to be carried out for all three environmental compartments, which are the aquatic compartment (including the sediment), the terrestrial compartment, and air. In practice however, many risk assessment schemes are limited to a number of protection goals, for example [4]:
Tab. 7.1. Definitions of the different steps comprised in an environmental risk assessment Hazard identification is the identification of the adverse effects, which a biocidal product has an inherent capacity to cause Dose (concentration)-response (effect) assessment is the estimate of the relationship between the dose, or level of exposure, of an active substance or substance of concern in a biocidal product and the incidence and severity of an effect Exposure assessment is the determination of the emissions, pathways, and rates of movement of an active substance or a substance of concern
in a biocidal product and its transformation or degradation in order to estimate the concentration/doses to which human populations, animals, or environmental compartments are or may be exposed Risk characterization is the estimation of the incidence and severity of the adverse effects likely to occur in a human population, animals, or environmental compartments due to actual or predicted exposure to any active substance or substance of concern in a biocidal product. This may include „risk estimation“, which means the quantification of that likelihood
7.2 Exposure Assessment * * * * *
the aquatic ecosystem (including the sediment as well as marine ecosystems); the terrestrial ecosystem; top predators; micro-organisms in sewage treatment systems; the atmosphere.
The general principles of environmental risk assessment apply to biocidal substances as for any other chemical substance. In the European Union, the decision was therefore taken to adapt the already existing guidance documents on the risk assessment of industrial substances [4] so that they can be used as a reference for the risk assessment of biocidal active substances. Further guidance on the supplementary risk assessment of the marketed biocidal product is currently being developed [5].
7.1.3
Risk Assessment and Data Requirements
Data requirements for any authorization scheme for biocides should be aimed at establishing the hazard profile and the potential exposure allowing a meaningful risk assessment of the active substance and the corresponding products. As a prerequisite it is necessary to know beforehand the exposure implication of the use of a given product. This will allow one to identify the primary target compartments for which an in-depth risk assessment needs to be performed, and hence for which higher tier test results might be necessary. The following description of the risk assessment process is applicable to single active substances or other substances of concern contained in the biocidal product. Further considerations for the assessment of biocidal products (the preparation, which is placed on the market) are given in Section 7.4.
7.2
Exposure Assessment
As for the assessment of any other chemical substance, the exposure assessment consists of the following three steps: * * *
release estimation; estimation of the environmental behavior; estimation of environmental concentrations.
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Fig. 7.1. Release pathways and receiving environmental compartments from local releases of an industrial site, from [4]
Before launching the exposure assessment, the release pathways and the receiving environmental compartments need to be defined. In Figure 7.1, a classical example for a local industrial setting is presented. According to the scheme in Figure 7.1, based on the local releases of a substance to air and waste water, its partitioning and degradation behavior in a sewage treatment plant (STP), air, soil, and surface water, the local concentrations (in the immediate vicinity of the industrial site) can be estimated in surface water, sediment, air, soil, and groundwater. Soil (agricultural soil or prairie) is supposed to receive input from atmospheric deposition and sewage sludge applied as fertilizer. Exactly the same settings can be used for substances used on a private or domestic basis, by replacing the industrial site with a town releasing its waste water to a single STP. Also urban or industrial soils can be considered on a case by case basis. For treated material in use, the same settings can also be used if the material or articles give rise to diffuse releases to waste water. Specific settings need to be defined for treated material used outdoors, from which a substance can be released locally to soil or surface water. For example, for treated wood, representative uses, for example wooden fences (Figure 7.2) or jetties in a lake can be defined.
7.2 Exposure Assessment
Fig. 7.2. Size of compartment receiving the leachate from a wooden fence treated with wood preservatives in a local exposure assessment
7.2.1
Release Estimation
The first step of the exposure assessment of an active biocidal substance consists of identifying all the possible releases to the environment resulting from the use of the biocidal product. This is done systematically for all life-cycle stages of the active substance (cradle-to-grave approach). The relevant life-cycle stages are illustrated in Figure 7.3. After chemical synthesis of the active substance and formulation of the biocidal product, the product can be used in an industrial or private setting as a processing aid or for the treatment of articles. Furthermore releases to the environment are possible during the service life of the treated articles as well as during elimination or recycling of the biocidal product or the treated articles having become waste. Regulatory schemes often focus on the application and subsequent life-cycle steps of the product or active substance. According to the EU-BPD, potential risks arising from chemical synthesis of the active ingredient and formulation of the biocidal product can be assessed if it is considered necessary. From the viewpoint of risk assessment it makes indeed no sense to exclude any life-cycle stages from the assessment, as the releases from all uses and life-cycle stages contribute to the overall environmental burden. Once all potential releases to the environment of the active substance have been identified, the releases to air, soil, and waste water need to be quantified. The quantity of a substance released to an environmental compartment depends on its physicalchemical properties, but mainly on the application method or the technological process involved in the use of the substance. For given application methods or technological processes, so-called “emission scenarios” can be developed. An emission scenario can be defined as a set of conditions about sources and use patterns that quantify the emissions (or releases) of a chemical [6, 7]. These generic scenarios are meant to be representative for a certain operation and therefore applicable to every site (industrial or other) where this operation is performed. Since the operation conditions (for example water consumption) vary from site to site, they can be chosen to estimate an emission that:
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Fig. 7.3. Schematic representation of the life cycle of a substance (adapted from [4])
* *
* *
likely exceeds actual emissions (a “bounding” or “worst-case” estimate); is representative of the “high end” of actual releases (a “reasonable worst-case” estimate, the 90th percentile is often used); is representative of “typical” exposures, or; cover the complete set of actual release values resulting from those conditions.
A “reasonable worst-case” approach is usually used. Many international activities aim at elaborating comprehensive and representative emission scenario documents. A catalogue of scenarios published in literature or used by authorities in national authorization schemes has been published in [8]. At OECD-level, a program has been launched, based on national documents, to develop emission scenarios, which are as representative as possible regarding use patterns and technologies used in OECD countries, and which can be used for internationally valid risk assessments. In the European Union, emission scenarios for industrial chemical substances as well as for biocidal substances are continuously developed for inclusion into the Tech-
7.2 Exposure Assessment
Fig. 7.4. Schematic representation of different cooling water systems (adapted from [10])
nical Guidance Document for risk assessment of new and existing industrial chemicals as well as active biocidal substances (TGD) [4]. Ultimately, emission scenarios need to be available for all 23 product types defined in the EU-BPD. For illustrative purposes, a simplified example of an emission scenario for biocides aimed at the treatment of cooling waters is presented below. For once-through systems (see Figure 7.4), which are continuously treated with a biocidal product, the release to surface water can be estimated as shown in Table 7.2 and the following calculation (Equation 1). Tab. 7.2. Input and output parameters for a release scenario for biocidal substances used in once-through cooling systems Variable/parameter [unit]
Symbol
Unit
Application rate of active substance
Qactive
Kg m–3
Flow of the cooling water
Qcooling water
m3 d–1
Fraction of substance degraded during the treatment
Fdeg
–
Elocalwater
Kg d–1
Default
Input:
Output: Local emission with the spent cooling water
0
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Model calculation: Elocalwater=Qcooling water*Qactive*(1–Fdeg)
(1)
While the application rate is substance specific, the flow rate of the cooling water is site-specific. In order to choose a representative default value for this parameter, statistical data regarding the use of cooling water in industry would need to be available. A slightly more complex scenario can be elaborated for re-circulation systems with cooling towers [9].
7.2.2
Environmental Behavior
After entering the environment, chemicals are transported and may be degraded or transformed into other chemicals. There are no methodological differences in assessing the environmental behavior of a biocidal active substance compared with any other chemical substance. The partitioning of a substance within and between compartments as well as its degradation or transformation in each compartment need to be quantified for an exposure assessment. Transport within or between Compartments Substances can be transported within an environmental compartment (intra-media transport) or from one environmental medium to another (inter-media transport). Transport takes place through the mechanisms of advection (travel from one place to another as a result of the flow of the medium in which it occurs) and dispersion (substances move down concentration gradients until the concentration gradients disappear. In systems that consist of more than one phase (for example soil or sediment), chemicals tend to migrate from one phase to another if the phases are not in equilibrium. At equilibrium, the ratio between the concentrations in two phases is constant if the concentrations are sufficiently low. This ratio is called the “equilibrium partitioning coefficient” between the two phases. If the concentration in one phase is known, the concentration in the other phase at equilibrium can be estimated with the corresponding equilibrium partitioning coefficient. A brief summary of the most important partition coefficients used in environmental risk assessment is presented in Table 7.3. Detailed estimation methods of the partition coefficients listed in Table 7.3 can be found for example in [4] and [11]. Some simple estimation methods are described below for some equilibrium partitioning coefficients. 7.2.2.1
7.2 Exposure Assessment Tab. 7.3. Main equilibrium partitioning coefficients for modeling the environmental transport of a substance Partition coefficient
Examples of use in an exposure assessment
air/water
* * *
solids/water
* * *
air/solids
* * *
volatilization rate from surface water stripping rate from sewage treatment plants wet atmospheric deposition adsorption onto soil, sediment, suspended matter, and sewage sludge leaching rate from soil to groundwater burial rate in sediment adsorption onto aerosols in the atmosphere volatilization rate from dry soil dry atmospheric deposition
air/biota
*
accumulation in plants via air
water/biota
*
accumulation in aquatic biota (fish, crustaceans,...) accumulation in roots of plants accumulation in terrestrial invertebrates
* *
Air-Water The air-water partition coefficient or the Henry’s law constant can be estimated from the respective water solubility and vapor pressure (Equations 2 and 3).
HENRY ¼
VP MOLW SOL
ð2Þ
Kairwater ¼
HENRY R TEMP
ð3Þ
with: VP MOLW SOL R TEMP HENRY Kair-water
vapor pressure [Pa] molecular weight [g mol–1] solubility [mg L–1] gas constant [Pa m3 mol–1 K–1] temperature at the air-water interface [K] Henry’s law constant [Pa m3 mol–1] air-water partitioning coefficient [-]
Other estimation methods for example based on group or bond contributions can also be used [12, 13]. Solids-Water The partitioning between solids and water is often based on the organic carbon/water partitioning coefficient Koc. Internationally harmonized laboratory methods are avail-
able for measuring the Koc in soil and sediment [14]. The laboratory methods consist
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of batch techniques where amounts of soil or sediment are added to an aqueous solution containing the substance. After agitation and separation of the phases, the concentration of the substance is measured in one or two phases. Very specific partitioning behavior can also be determined in simulation tests. For example, the leaching from soil to groundwater can be determined in lysimeter studies. Using the Koc for estimating the solids-water partitioning coefficient is most appropriate for neutral, hydrophobic organic substances. Nevertheless, this approach has been applied to a wide variety of substances as it works reasonably well. For substances interacting specifically with the sorbate, for example, with the mineral fraction of the solids, a more specific correlation between sorbate and sorbent might need to be derived. Based on the Koc, the solids/water partition coefficient can be estimated for different compartments (Equation 4). Kpcomp ¼ foccomp *Koc
ð4Þ
With: Kpcomp solids-water equilibrium partitioning coefficient [L kg–1] comp E {soil, sediment, suspended matter, sewage sludge} foccomp organic carbon content of the medium [-] Koc organic carbon/water equilibrium partitioning coefficient [L kg–1] The organic carbon–water partitioning coefficient Koc can also be estimated with (Q)SARs. Most developed (Q)SARs establish a relationship between the Koc and the n-octanol–water partitioning coefficient Kow. The experimental determination of the Kow is indeed required in most biocidal product authorization schemes. An overview of estimation methods can be found in [4] and [11]. For example, regression models to estimate Log Koc from Log Kow, valid for a wide variety of substances are presented below (Equations 5 and 6). Wide variety of substances [15] Log Koc=0.679 Log Kow+0.663 Nonhydrophobic substances [16] Log Koc=0.52 Log Kow + 1.02
(5) (6)
Other relationships have been derived for specific classes of chemical substances, for example, alcohols, amides, anilines [11]. Furthermore, for ionizable substances, a correlation has been developed to directly estimate the soil-water partitioning coefficient Kpsoil using Log Kow, pKa, soil pH, and the organic carbon content of the soil focsoil [17]. Water-Biota The biota-water partitioning coefficient or bioconcentration factor (BCF, ratio of the
substance concentration in an organism to the concentration in water) will allow the estimation of the concentration of a substance in aquatic organisms and hence the
7.2 Exposure Assessment
exposure to potential predators as for example fish-eating birds as well as humans. Several laboratory methods are available to experimentally determine the BCF in fish or crustaceans [18, 19]. Furthermore many estimation methods based on (Q)SARs are also available [4, 11]. Equilibrium partitioning models assume that chemicals reach an equilibrium between the organisms and water and ignore dietary uptake. These estimation methods establish a relationship between the lipophilicity of a substance (expressed as its Kow) and its accumulation in the fat of aquatic organisms. For substances with a Log Kow <6, similar linear regression models between Log Kow and Log BCF have been proposed by many authors [20 – 22]. The model recommended in [4] and developed by [20] on BCF data for fathead minnows (Pimephales promelas) is presented below in Equation 7. log BCF=0.85 log Kow–0.7
(7)
For substances with a very high hydrophobicity (log Kow >6), experimental BCF results indicate that linear regression models do not apply. This could on one hand be explained by experimental shortcomings, for example insufficiently long test duration as steady-state is achieved very slowly with very hydrophobic substances, which are eliminated very slowly from organisms. On the other hand, higher molecular weight and size of very hydrophobic substances could cause slow membrane permeation kinetics and thereby low BCFs. Bilinear, parabolic or polynomial regression models have been proposed by several authors [23 – 26]. Two models are recommended in [4] for substances with log Kow >6. They have been developed by [23] and are presented below in Equations 8 and 9. log BCF = 6.9 x 10–3 (log Kow)4 – 1.85 x 10–1 (log Kow)3 + 1.55 (log Kow)2 – 4.18 log Kow + 4.79
(8)
or log BCF = –0.20 (log Kow)2 + 2.74 log Kow – 4.72
(9)
7.2.2.2 Transformation and Degradation Processes
The following degradation and transformation processes, which can occur in the environment, are most relevant for an exposure assessment: * * *
biodegradation; hydrolysis; direct or indirect photodegradation.
Laboratory tests aimed at estimating the degradation velocity of an active substance by these processes are required in most authorization schemes. A substance is first degraded or transformed into primary degradation products or metabolites (primary
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degradation), which themselves can be further degraded. Some transient transformation products will appear for a very short duration only while others will be degraded much slower than the parent compound. The EU-BPD requests that all relevant transformation products are identified in laboratory tests on hydrolysis, photodegradation as well as biodegradation simulation tests. Ideally all degradation products would need to be assessed for their impact upon the environment. In practice however, only the most stable breakdown products are assessed. For exposure assessment purposes, it is necessary to determine the degradation velocity of active substances released to the different environmental compartments. Among the most relevant transformation rates to ascertain are the biodegradation rate in sewage treatment plants (STPs), surface water, sediment, and soil. A tiered approach can be proposed. For example, a testing strategy for biodegradability elaborated for the implementation of the EU-BPD is presented in Figure 7.5.
Fig. 7.5. Testing strategy for establishing the biodegradation behavior of active substances in different environmental compartments according to [27]
7.2 Exposure Assessment Tab. 7.4. Half-lives of readily degradable substances in different compartments assuming first order kinetics, as proposed by [4] Compartment
Half-life (DT50), function of the adsorption coefficient Kpsoil
Sewage treatment plant
–
Surface water
–
Soil and aerobic sediment
Kpsoil100 L kg
1.4 hours 15 days –1
30 days
100
300 days
1000
3000 days
In a first step, substances can be tested in screening assays on “ready biodegradation”. These are very stringent tests with a high substance/inoculum ratio and the test substance as sole carbon source. They provide limited opportunity for biodegradation and acclimatization to occur. Harmonized international test guidelines have been published by the OECD (OECD guidelines 301 A–F [28]). A “readily degradable” substance will rapidly mineralize in the environment and the probability of the formation of stable metabolites in the environment is very low. Half-lives in the different environmental compartments have been proposed in [4] for “readily biodegradable” substances as shown in Table 7.4. For soil and sediment, the degradation rates are dependent on the partitioning behavior as the bioavailability of the substance will be reduced due to adsorption onto solids. Comparable half-lives have been proposed by [29]. For biocides, especially disinfectants, toxicity towards the inoculum can prevent biodegradation in assays on ready biodegradation due to the high test substance concentration. Lowering the test concentration is not acceptable, as the stringency of the test would be altered. Test systems simulating environmental conditions (see below) would need to be used instead. For substances proving to be not “readily biodegradable”, screening tests on “inherent biodegradation” can be performed. These test systems (for example OECD guidelines 302 A–C [28]) operate under optimized conditions with higher inoculum concentrations and/or longer test durations. For substances which do not degrade in these systems (no ultimate or primary degradation), it can be assumed that they are not degraded in the environment either. No further testing is needed. Observed degradation in these test systems is very difficult to extrapolate towards environmental compartments. Furthermore they do not foresee identification or quantification of intermediate transformation products. Therefore, for substances, which are not “readily biodegradable”, but which degrade to some extent in test systems on inherent biodegradability, it is necessary to perform biodegradation tests which simulate environmental conditions at test concentrations close to those which can be expected in the environment. Depending on the release
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pathways, the following simulation test methods could be recommended if a preliminary risk assessment indicates a high risk potential: *
*
*
Sewage treatment plant: OECD Guideline 303A “Simulation test–aerobic sewage treatment” [30]. The method can be adapted to allow for a complete mass balance as well as the identification of all relevant degradation products. Surface water: ISO/DIS Guideline “Evaluation of the aerobic biodegradability of organic compounds at low concentrations” [31, 32]. Soil: OECD Guideline 307 “Aerobic and anaerobic transformation in soil” [33].
Depending on the partitioning properties of the substance, its degradation behavior in indirectly exposed compartments could also be determined. For example, for a lipophilic substance released to surface water, partitioning to sediment will occur and its degradation behavior in sediment can be determined for example according to the OECD water sediment test [32].
7.2.3
Environmental Concentrations
In the last step of the exposure assessment, the concentrations in the receiving compartments are estimated.
Surface Water and Sediment Release estimation (see Section 7.2.1) is usually aimed at determining the releases to waste water. Before reaching the surface water, the effluent will probably be treated in a biological sewage treatment plant (STP), either on-site or off-site in a municipal waste water collection system. As shown in Section 7.2.2.2, simulation tests will allow one to estimate the elimination of a substance in a full size STP. For some substances, measurements in full size STPs will even have been performed, which will allow a realistic estimation of the behavior of a substance in any biological STP. In the absence of any information, mathematical models can be used. These kind of models have been proposed for example by [35] or [36]. Based on simple properties of the substance (octanol/ water partition coefficient, Henry’s law constant, degradation rate constant), the elimination by degradation, stripping and adsorption on to sewage sludge can be estimated. For a generic risk assessment, a default waste water flow rate needs to be set. In [4], a value of 2000 m3 d–1 is proposed, which corresponds to a STP treating the waste water of a small town of approximately 10 000 inhabitants. The remaining fraction of the concentration of the substance will be released with the effluent into the receiving surface water (river, lake, estuary, marine coastal area). 7.2.3.1
7.2 Exposure Assessment
Fig. 7.6. Transport and degradation processes, which influence the local concentration in surface water, according to [4]
On a local scale, in the immediate vicinity of the point of release, the processes, which have the biggest influence on the resulting local water concentration, are dilution and adsorption onto suspended matter (see Figure 7.6). Volatilization and degradation will have little influence, especially in rivers, where the effluent is rapidly transported downstream. With these assumptions, a local dissolved concentration in the receiving surface water can be estimated according to Equation 10. PEClocalwater ¼
Clocaleff ð1 þ Kpsusp SUSPwater 106 Þ DILUTION
With: Clocaleff Kpsusp SUSPwater DILUTION PEClocalwater
concentration of the chemical in the STP-effluent [mg L–1] solids-water partitioning coefficient of suspended matter [L kg–1] concentration of suspended matter in the river [mg L–1] dilution factor [-] local concentration in surface water [mg L–1]
ð10Þ
The corresponding concentration in sediment can be estimated according to Equation 11. PEClocalsed ¼ With: PEClocalaqua RHOsed
Ksed-water PEClocalwater 1000 RHOsed concentration in surface water [mg L–1] bulk density of wet sediment [kg m–3]
ð11Þ
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Ksed-water PEClocalsed
sediment-water equilibrium partitioning coefficient [m3 m–3] predicted environmental concentration in sediment [mg kg–1]
The partition coefficient and properties for suspended matter can also be used in Equation 11 for an estimation of the concentration in freshly deposited sediment. 7.2.3.2 The Atmosphere
The atmospheric concentration in the vicinity of a point source can be estimated with rather simple mathematical models, assuming a Gaussian diffusion of the effluent plume along the wind direction, as shown in Figure 7.7. The concentration in the plume at a certain distance from the source can be used to estimate the risks to humans or animals living in the vicinity of industrial sites. The atmospheric deposition to soil can also be determined by estimating the aerosol–air partition coefficient and the gaseous and aerosol deposition velocities. Estimation methods are described in [37-39]. 7.2.3.3 Soil
As shown in Section 7.2 (Figure 7.1), routinely assessed inputs into soil are: * *
atmospheric deposition; application of sewage sludge as fertilizer.
Other situations have to be assessed for biocides, for example: * * * *
leachate from fences treated with wood preservatives; termiticides applied onto soil around houses; leachate from facades treated with masonry preservatives; soil disinfectants used for human or animal hygiene purposes.
Fig. 7.7. Gaussian distribution of a plume from a point source, according to [38]
7.2 Exposure Assessment
Removal processes from the upper soil surface can be volatilization, degradation, and leaching to groundwater (Figure 7.7). A simple model for the estimation of the concentration in the upper soil layer has been proposed by [39]. For continuous releases to soil (for example, through atmospheric deposition or input of leachate from treated wood), the equilibrium concentration in soil can be estimated according to Equation 12. PEClocalwater ¼ With: PEClocalsoil DEPtotalann DEPTHsoil RHOsoil k
DEPtotalann DEPTHsoil RHOsoil k
ð12Þ
predicted environmental concentration in soil [mg kg–1] annual average total deposition flux [mg m–2 d–1] mixing depth of soil [m] bulk density of wet soil [kg m–3] first order rate constant for removal from top soil [d–1]
For discontinuous emissions (for example the repeated spreading of sewage sludge onto agricultural land), the build-up over the years have to be taken into account. A corresponding calculation method is proposed in [4] (see Figure 7.8). The concentration of a substance in groundwater can be assimilated, in a very preliminary approach, to the concentration in interstitial water in the upper soil layer, as shown in Equation 13. PEClocalsoil, porew ¼
PEClocalsoil RHOsoil Ksoil, water 1000
Fig. 7.8. Possible fate processes in the soil compartment, according to [4]
ð13Þ
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With: PEClocalsoil RHOsoil Ksoil-water PEClocalsoil,porew
predicted environmental concentration in soil [mg kg–1] bulk density of wet soil [kg m–3] soil-water equilibrium partitioning coefficient [m3 m–3] predicted environmental concentration in porewater [mg L–1].
More sophisticated models have been developed in the context of the risk assessment of pesticides. Many national models are available, for example, [40], [41], or [42]. These models can be used for refinement of the soil exposure assessment (concentration in the upper soil layer as well as in groundwater).
7.3
Effects Assessment
In practice, the effects assessment for the environment consists of establishing a Predicted No Effect Concentration (PNEC) for each relevant environmental compartment. According to [4], “a PNEC is regarded as a concentration below which an unacceptable effect will most likely not occur”. The two methods most frequently described to establish PNECs for chemical substances are described below. 7.3.1
Uncertainty Factors for Establishing PNECs
For a given compartment, the PNEC can be extrapolated from results of laboratory assays performed on single species from that compartment. This approach assumes that * *
the sensitivity of the ecosystem depends on the most sensitive species; the protection of the structure of the ecosystem insures the protection of the functioning of the ecosystem.
The test results for the most sensitive species towards a given substance are used to calculate a PNEC. If this species is protected, it can be considered that the function and the structure of the whole ecosystem are protected. The extrapolation from the effects upon one species towards an ecosystem can be achieved with uncertainty factors. These factors need to take into consideration: *
*
the variation within a given laboratory and between different laboratories performing the assays; intra-species variations due to the physiological state of the individuals of a same species;
7.3 Effects Assessment *
*
*
inter-species variations, that is the differences of sensitivities towards a substance of different species belonging to the ecosystem; the extrapolation of the acute or short-term toxicity towards long-term or chronic toxicity. Sub-lethal effects can appear after a long exposure duration and endanger a population, without it being detected over the short term; the extrapolation of laboratory results towards the field.
The uncertainty factors are applied to cover all the variations and uncertainties listed above. The size of the factor depends on the quantity and quality of information available for the ecosystem. If test results on the ecotoxicity of a substance towards many species belonging to different taxonomic groups and trophic levels are available, the uncertainty factor will be lower compared to a substance for which only few test results are available. The Aquatic Ecosystem In Table 7.5, the scheme for establishing a PNEC for the aquatic ecosystem as proposed for the EU-BPD is presented. The PNEC is calculated by dividing the L(E)C50 or NOEC from the most sensitive species towards the substance with the appropriate uncertainty factor. Other schemes, with similar uncertainty factors, have been proposed by [43] and [44]. The long-term toxicity results are used for deriving a PNEC only if they are found for the most sensitive species identified from the acute toxicity results. Otherwise it might be more appropriate to use the acute toxicity results with a factor of 1000. On the other hand, the scheme can be used with a certain amount of flexibility. For example, if many test results with many different species are available, lower uncertainty factors can be chosen. 7.3.1.1
Tab. 7.5.
Uncertainty factors for establishing a PNEC for the aquatic compartment
Available information
Uncertainty factor
At least one short-term L(E)C50 from each of three trophic levels (fish, invertebrates, and algae)
1000
One long-term NOEC (either fish or invertebrates)
100
Two long-term NOECs from species representing two trophic levels (fish and/or invertebrates and/or algae)
50
Long-term NOECs from at least three species (normally fish, invertebrates, and algae) representing three trophic levels
10
Field data or data from model ecosystem
Reviewed on a case by case basis
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The Sediment A similar assessment scheme with uncertainty factors can be imagined for the benthic ecosystem. As benthic organisms can be exposed via interstitial water as well as through the ingestion of sediment, the pathways through which the test organisms are exposed are very relevant. In addition to choosing test organisms of different benthic taxa and life-stages, it is necessary to choose species representing different habitats and feeding strategies, which are exposed to sediment-bound substances by different exposure pathways. Furthermore, long-term tests with sublethal endpoints like reproduction, growth, emergence, sediment avoidance, and burrowing activities are regarded as most relevant. In the absence of experimental data for benthic organisms, a provisional PNEC for the benthic ecosystem can be estimated by the equilibrium partitioning method. This method uses the PNEC derived for the aquatic ecosystem and the sediment/water partitioning coefficient [45, 46]. It assumes that: 7.3.1.2
*
*
Benthic organisms and water column organisms are equally sensitive to the substance. The concentration of the substance in sediment, interstitial water, and benthic organisms are at a thermodynamic equilibrium.
Based on these assumptions, a PNEC for the benthic ecosystem can be estimated according to Equation 14. PNECsed ¼ With: PNECaqua RHOsed Ksed-water PNECsed
Ksed-water PNECaqua RHOsed
ð14Þ
Predicted No Effect Concentration in water [mg m–3] bulk density of wet sediment [kg m–3] sediment/water equilibrium partitioning coefficient [m3 m–3] Predicted No Effect Concentration in sediment [mg kg–1]
The Terrestrial Ecosystem An uncertainty factor approach can also be derived for the soil compartment. Table 7.6 presents the scheme for establishing a PNEC for the soil ecosystem as proposed for the EU-BPD. The data requirements within the EU-BPD [27] ensure that at least the acute toxicity data are available to derive a PNEC for soil whenever there is a high potential for exposure of the soil compartment. In the absence of any test result with soil organisms, the equilibrium partitioning method as described above for sediment can be used for a screening assessment (Equation 15). 7.3.1.3
7.3 Effects Assessment Tab. 7.6.
Uncertainty factors for establishing a PNEC for the soil compartment
Available information
Uncertainty factor
L(E)C50 from short-term toxicity tests (e.g. plants, earthworms, or micro-organisms)
1000
NOEC from one long-term toxicity test (e.g. earthworms)
100
NOECs for additional long-term toxicity tests of two trophic levels
50
NOECs for additional long-term toxicity tests for three species of three trophic levels
10
Field data or data from model ecosystem
PNECsoil ¼ With: PNECaqua RHOsoil Ksoil-water PNECsoil
Reviewed on a case by case basis
Ksoil-water PNECaqua RHOsoil
ð15Þ
Predicted No Effect Concentration in water [mg m–3] bulk density of wet soil [kg m–3] soil/water equilibrium partitioning coefficient [m3 m–3] Predicted No Effect Concentration in soil [mg kg–1]
The equilibrium partitioning method is not recommended for biocides with a specific mode of action. Testing on soil organisms could be required if there is direct exposure to soil. 7.3.2
The Statistical Extrapolation Method
A statistical method to extrapolate a PNEC from ecotoxicity results has been proposed [47-49]. This method addresses situations where a large number of NOECs are available for a substance. Indeed, the uncertainty factor system invariably proposes to use a fixed factor independently of the number of available NOECs, be it 3 or 30, while the uncertainty in extrapolating a PNEC decreases with the number of species tested. The statistical method supposes that the NOECs observed with different species follow a log-logistic or log-normal distribution. The PNEC can then be chosen as the concentration for which the probability to find a NOEC lower than the PNEC is for example 0.05 (see also Figure 7.9). To use this method, it is necessary that a series of NOECs from different species is available. If several NOECs are available for the same species, the geometric mean of these values can be used for example, to avoid an overrepresentation of that species in the distribution. The minimum number of NOECs which needs to be available to apply the statistical extrapolation method is subject to an ongoing debate. A minimum number of 4 NOECs has been proposed [50], but preferably many more should be available.
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Fig. 7.9. The logistic density function and estimation of the concentration at which the NOEC of no more than p% of the species within an ecosystem is exceeded. According to [51] with permission
7.4
Regulatory Decision-making 7.4.1
Risk Characterization
Having estimated all PNECs for all exposed compartments and all PECs for all relevant uses and life-stages, the risk characterization ratios PEC/PNEC are calculated. If all risk characterization ratios (RCRs) are lower than 1, it can be considered that the risk for the environment is acceptable. The active substance can be considered for authorization for biocidal uses which have been assessed. If one or more RCRs are higher than 1, the underlying data of the assessment needs to be re-evaluated for its influence upon the RCR. If there is a high probability that further test results or further information could improve the reliability of the risk assessment and lower the RCRs, further information can be requested. The following additional data requests could be imagined for example: *
*
long-term toxicity tests with aquatic organisms allowing one to lower the uncertainty in deriving a PNEC for the aquatic ecosystem; screening toxicity tests with soil organisms allowing one to derive a more realistic PNEC for the soil ecosystem compared to the PNEC estimated by the equilibrium partitioning method;
7.4 Regulatory Decision-making *
*
measuring the concentration of the substance in effluents of representative sites using the substance; an experimentally determined BCF in fish allowing a more realistic exposure assessment for predators compared to an exposure assessment based on a BCF estimated by (Q)SARs;
As indicated in Section 7.2.1, most estimation methods used in risk assessment are chosen to represent a “realistic worst case” situation. By combining several estimation steps, the result could become overly conservative and therefore leading to high RCRs. By replacing some of the estimations by experimentally determined results, the risk assessment will become more realistic and the RCRs will usually be lowered. If the probability of lowering the RCRs below 1 with additional information is low, it can be concluded that the substance represents an unacceptable risk to the environment and that it should not be considered for authorization for biocidal uses. However, not all uses might represent a risk, at least not after risk mitigation measures. An active substance could be authorized for a use in contained systems giving rise to low releases to the environment, while more open uses would induce unacceptable risks. The risk characterization process is summarized in Figure 7.10.
7.4.2
Risk Assessment of Biocidal Products
The EU-BPD requests that the risks from products are assessed. For products consisting of an active substance with a simple diluent, the assessment of the active substance is sufficient to cover the risks from the product. A different approach is needed for products containing two or more active substances. An interaction between the active
Fig. 7.10. process
Schematic representation of the risk characterization
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substances could indeed result in synergistic effects which would remain unaccounted for if the active substances were assessed separately. The same situation arises if the product contains a diluent or another component enhancing the bioavailability of the active substance. It could then be argued that it is necessary to test the effects of products towards ecosystems whenever it is apparent that there is an interaction between the components of the product. However, upon release into the environment, the individual components will usually have very different transport and transformation behavior. The integrity of the initial composition of the product will not be maintained. Thereby the interaction between the constituents will be disrupted as well. Even before reaching the environment, the composition of the product will be changed. For example, after application of a wood preservative product, some ingredients will interact with the wood. If the treated wood is used in contact with water, the leaching rate out of the wood will be specific to each of the components. The relative concentration of each component in the leachate from the wood will be very different from its relative concentration in the initially applied product. In other situations, a more direct contact of a biocidal product with an environmental compartment is possible. For example, a masonry preservative applied by spraying of aerosols can give rise to spray drift and deposition onto soil. In the same way, the use of a cooling water preservative in a once-through system can cause direct release of all product components in their respective initial composition to surface water. Two distinct approaches towards assessing products can therefore be proposed. For products whose composition changes radically before reaching an environmental compartment, all relevant components of the product need to be assessed separately, which means that PEC/PNEC ratios need to be estimated for each component. For complex mixtures, a risk assessment scheme has been proposed for petroleum substances [4]. For aromatic and aliphatic hydrocarbons, it can usually be assumed that they act by the same mode of action upon aquatic organisms, namely by nonpolar narcosis and that the contribution of each component to the risk of the product is therefore additive. A PEC/PNEC ratio for the product in a compartment can be estimated according to Equation 16.
PEC PNEC
product
¼
X PEC PNEC components
ð16Þ
A recently published literature review [52] has shown that this “concentration addition” model is also valid for mixtures of pesticidal active substances. Based on test results on different aquatic organisms from 202 mixtures of two or more pesticidal active substances, the “concentration addition” model predicts correct effect concentrations (within a factor of two) compared to the experimental results for more than
7.4 Regulatory Decision-making
90 % of the mixtures. Even for combinations of compounds with presumably dissimilar modes of action, correct results were predicted for more than 90 % of the mixtures. It can therefore also be suggested that the “concentration addition” model is used tentatively for biocidal products. For products for which a direct exposure to a given compartment is possible, test results with whole products can be taken into account. A PEC and a PNEC can be derived for the whole product as for a single substance and a corresponding risk characterization can be performed for the product (Equation 17).
PEC PNEC
product
¼
X PECproduct
PNECproduct
ð17Þ
The approach is usually not possible throughout a risk assessment for all compartments. For example, for a product being released by aerosol to agricultural soil, the risk characterization for soil might be performed based on test results with the product, but the indirect exposure of humans via vegetables grown on this soil can only be performed component by component. 7.4.3
Other Criteria
As shown in Section 7.4.1, the outcome of the risk characterization for the active substance is the main endpoint for deciding on the approval of an active substance. In addition to a quantitative risk assessment, further decision criteria can be used for approval of active substances and biocidal products. 7.4.3.1
Persistence, Bioaccumulation, and Toxicity
For substances being highly persistent, bioaccumulative and toxic, the uncertainty of the risk assessment increases significantly. For example, for substances with a logKow higher than 5 or a BCF higher than 5000, a high potential for biomagnification has to be assumed [53]. Food web biomagnification models have so far only been validated with organochlorine chemicals, mainly polychlorinated biphenyls [11]. The adverse effect upon predators can therefore only be assessed with a high degree of uncertainty. While international conventions already address substances being simultaneously highly persistent, bioaccumulative and toxic, national or regional approval schemes for biocidal substances may implement more severe decision schemes. The EU-BPD sets specific criteria for nonapproval of active substances based on their persistence and potential for bioaccumulation.
191
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For example, a biocidal product containing an active substance, which persists in soil for more than a year in field tests or, which forms nonextractable residues during laboratory tests in amounts exceeding 70 % of the initial dose after 100 days with a mineralization rate of less than 5 % in 100 days cannot be approved, unless it is scientifically demonstrated under field conditions that there is no unacceptable accumulation in soil. Further conditions on persistence in other compartments as well as on bioaccumulation in aquatic and terrestrial organisms are included in the EU–BPD and further explained in a corresponding guidance document [54]. Although risk assessment methodologies are constantly improved, these additional decision criteria ensure that substances, for which the risk assessment might be subject to a high level of uncertainty, are excluded from the use in biocidal products. 7.4.3.2 Comparative Assessment
To minimize even more the impact of biocidal substances upon man or the environment, it could be decided to further restrict the number of active substances authorized for use in biocidal products. The EU-BPD, for instance, states that the authorization of an active substance may be refused “if there is another active substance [...] for the same product type which, in the light of scientific or technical knowledge, presents significantly less risk to health or to the environment”. The chemical diversity of the authorized active substances has to be adequate in order to minimize the occurrence of resistance in the target organism. The aim of such a disposition would be to encourage the development of active substances, which have a very specific activity towards the target organisms but has low or no effect upon nontarget organisms including humans.
7.4.4
Conclusion
The continuing activities in regulatory fora like the OECD or the European Union aiming at the further development and harmonization of risk assessment methodologies for chemical substances in general and of biocides in particular, indicate the importance that most countries attribute to risk assessment for regulatory decision-making. An in-depth science based risk assessment will indeed be the most realistic estimation of the real impact of a chemical substance upon the environment. On the other hand, risk assessment is a resource consuming process. The in-depth risk assessment for a given active substance or product can take months up to several years, and thereby postponing any regulatory decision. Furthermore the inherent uncertainties within a risk assessment can hinder the decision-making. Less time-consuming alternatives to risk assessment procedures are therefore continuously investigated as
References
well. As shown above in Section 7.4.3, decision-making schemes based on key environmental properties like persistence, bioaccumulation and toxicity are being adopted in many countries. It can reasonably be assumed that risk assessment procedures will continue to be developed and improved and play an important role in regulatory decision-making, while less time-consuming alternatives could be developed in parallel in the near future.
References
References
[1] Organization for Economic Co-operation and Development, Report of the Survey of OECD Member Countries’ Approaches to the Regulation of Biocides, OECD Environmental Health and Safety Publications. Series on Pesticides, No. 9, Paris, France, 1999. [2] Directive 98/8/EC of the European Parliament and Council of 16 February 1998 concerning the placing of biocidal products on the market, Off. J. Eur. Communities, L123, 1 – 63. [3] C.J. van Leeuwen, J.L.M. Hermens, Risk Assessment of Chemicals, An Introduction, Kluwer Academic Publishers, The Netherlands, 1995. [4] European Commission, Technical Guidance Document in Support of Commission Directive 93/67/EEC on Risk Assessment for New Notified Substances and Commission Regulation (EC) No 1488/94 on Risk Assessment for Existing Substances, Office for Official Publications of the European Communities, Luxembourg, 1996. [5] European Commission, Technical Guidance Document in Support of Annex VI of Directive 98/8/EC of the European Parliament and the Council Concerning the Placing of Biocidal Products on the Market, Common Principles and Practical Procedures for the Authorisation and Registration of Products, Draft Proposal, December 2000. [6] Organization for Economic Co-operation and Development, Guidance Document on Emission Scenario Documents, OECD Series on Emission Scenario Documents, No. 1, Paris, France, 2000. [7] R. Diderich, J. Ahlers, Risk Assessment of Existing Chemicals, Environ. Sci. & Pollut. Res. 1995, 2 (2), 116.
[8] W. Baumann, K. Hesse, D. Pollkla¨sner, K. Ku¨mmerer, T. Ku¨mpel, Gathering and Review of Environmental Emission Scenarios for Biocides, Institute for Environmental Research (INFU), University of Dortmund, 2000. [9] RIVM, VROM, VWS, Uniform System for the Evaluation of Substances 3.0 (USES 3.0). National Institute of Public Health and the Environment (RIVM), Ministry of Housing, Spatial Planning and the Environment (VROM), Ministry of Health, Welfare, and Sport (VWS), The Netherlands. RIVM report 601450 004, 1999. [10] H.P. van Dokkum, M.C.T. Scholten, D.J. Bakker, Development of a Concept for the Environmental Risk Assessment of Biocidal Products for Authorization Purposes (BIOEXPO),. Umweltforschungsplan des Bundesministers fu¨r Umwelt, Naturschutz und Reaktorsicherheit, Forschungsbericht 106 01 065, 1998. [11] R.S. Boethling, D. Mackay, Handbook of Property Estimation Methods for Chemicals, Environmental and Health Sciences, Lewis publishers, 2000. [12] J. Hine, P.K. Mookerjee, The intrinsic hydrophilic character of organic compounds. Correlations in terms of structural contributions, J. Org. Chem. 1975, 40 (3), 292 – 298. [13] W.M. Meylan, P.H. Howard, Bond Contribution Method for Estimating Henry’s Law Constants,. Environ. Toxicol. Chem. 1991, 10, 1283 – 1293. [14] Organization for Economic Co-operation and Development, Adsorption–Desorption Using a Batch Equilibrium Method, OECD Guideline for Testing of Chemicals 106, Paris, France, 2000.
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7 Environmental Safety and Risk Assessment [15] Z. Gerstl, Estimation of Organic Chemical Sorption by Soils, Journal of Contaminant Hydrology. 1990, 6, 357 – 375. [16] A. Sabljic, H. Gusten, H. Verhaar, J. Hermans, QSAR Modelling of Soil Sorption, Improvements and Systematics of log Koc vs. log Kow Correlations, Chemosphere, 1995, 31 (11/12), 4489 – 4514. [17] S. Bintein, J. Devillers, QSAR for Organic Chemical Sorption in Soils and Sediments, Chemosphere, 1994, 28 (6), 1171 – 1188. [18] Organization for Economic Co-operation and Development, Bioaccumulation: Flowthrough Fish Test, OECD Guideline for Testing of Chemicals, 305, Paris, France, 1996. [19] US-EPA, Oyster BCF, Ecological Effects Test Guidelines, OPPTS Number 850.1710, EPA Pub. no. 712-C-96-127, 1996. [20] G.D. Veith, D.L. Defoe, B.V. Bergstaedt, Measuring and Estimating the Bioconcentration Factor of Chemicals in Fish, J. Fish. Res. Board. Can. 1979, 36, 1040 – 1048. [21] D. Mackay, Correlation of Bioconcentration Factors, Environ. Sci. Technol. 1982, 16, 274 – 278. [22] P. Isnard, S. Lambert, Estimating Bioconcentration Factors from Octanol-Water Partition Coefficient and Aqueous Solubility, Chemosphere, 1988, 17, 21 – 34. [23] D.W. Connell, D.W. Hawker, Use of Polynomial Expressions to Describe the Bioconcentration of Hydrophobic Chemicals by Fish, Ecotoxicol. Environ. Safety 1988, 16, 242-257. [24] M. Nendza, QSARs of Bioconcentration: Validity Assessment of log Pow/log BCF Correlations, in Bioaccumulation in Aquatic Systems, eds R. Nagel, R. Loskill, VCH, Weinheim, Germany, 1991. [25] S. Bintein, J. Devillers, W. Karcher, Nonlinear Dependence of Fish Bioconcentration on n-Octanol/Water Partition Coefficient, SAR QSAR Environ. Res. 1993, 1, 29 – 39. [26] W.M. Meylan, P.H. Howard, R.S. Boethling, D. Aronson, H. Printup, S. Gouchie, Improved Method for Estimating Bioconcentration/Bioaccumulation Factor from Octanol/Water Partition Coefficient, Environ. Tox. Chem. 1999, 18, 664–672.
[27] European Commission, Technical Guidance Document in Support of Directive 98/8/EC of the European Parliament and the Council Concerning the Placing of Biocidal Products on the Market, Guidance on Data Requirements for Active Substances and Biocidal Products, Final Draft, October 2000. [28] Organization for Economic Co-operation and Development, OECD Guideline for Testing of Chemicals, Degradation and Accumulation, Paris, France, 1996. [29] R.S. Boethling, P.H. Howard, W.M. Meylan, W. Stiteler, J. Beaumann, N. Tirado, Group Contribution Method for Predicting Probability and Rate of Aerobic Biodegradation,. Environ. Sci. Technol. 1994, 28, 459 – 465. [30] Organization for Economic Co-operation and Development, Draft proposal for a new OECD Guideline for Testing of Chemicals 303A, Simulation Test–Aerobic Sewage Treatment: Activated Sludge Units, Paris, France, 2000. [31] ISO/DIS 14592-1, Evaluation of the Aerobic Biodegradability of Organic Compounds at Low Concentrations – Part 1: Shake-Flask Batch Test with Surface Water or Surface Water/Sediment Suspensions, draft guideline, 2000. [32] ISO/DIS 14592-2, Evaluation of the Aerobic Biodegradability of Organic Compounds at Low Concentrations – Part 2: Continuous Flow River Model with Attached Biomass, draft guideline, 2000. [33] Organization for Economic Co-operation and Development, Draft proposal for a new OECD Guideline for Testing of Chemicals 307, Aerobic and Anaerobic Transformation Soil, Paris, France, 2000. [34] Organization for Economic Co-operation and Development, OECD Guideline for Testing of Chemicals, Aerobic and Anaerobic Transformation in Aquatic Sediment, draft guideline, Paris, France, 1996. [35] J. Struijs, J. Stoltenkamp, D. Van De Meent, A Spreadsheet-Based Model to Predict the Fate of Xenobiotics in a Municipal Wastewater Treatment Plant, Wat. Res. 1991, 25 (7), 91 – 99. [36] C.E. Cowan, R.J. Larson, T.C.J. Feijtel, R.A. Rapaport, An Improved Model for Predicting the Fate of Consumer Product
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[45]
[46]
Chemicals in Wastewater Treatment Plants, Wat. Res. 1993, 27 (4), 561 – 573. J.A. Van Jaarsveld, An Operational Atmospheric Transport Model for Priority Substances; Specifications and Instructions for Use, RIVM report no. 222501002, 1990. Organization for Economic Co-operation and Development, Screening Assessment Model System (SAMS), version 1.1, Paris, France, 1992. European Center for Ecotoxicology and Toxicology of Chemicals, HAZCHEM, A Mathematical Model for Use in Risk Assessment of Substances, ECETOC Special report No. 8, Brussels, Belgium, 1994. M. Leistra, A.M.A. Van der Linden, J.J.T.I. Boesten, A. Tiktak, PEARL, A One-Dimensional Model for Pesticide Behavior in Soil. 1. Process Description, Report RIVM and DLO Winand Staring Center, in prep., 2000. M. Klein, Pesticide Leaching Model (PELMO), Fraunhofer Institut fu¨r ¨ kotoxicologie, Umweltchemie and O Schmallenberg, Germany, 1993. N. Jarvis, MACRO, Swedish Environmental Protection Agency, Stockholm, Sweden, 1993. Organization for Economic Co-operation and Development, Report of the OECD Workshop on the Extrapolation of Laboratory Aquatic Toxicity Data to the Real Environment, OECD Environment Monographs 59, Paris, France, 1992. European Center for Ecotoxicology and Toxicology of Chemicals, Environmental Hazard Assessment of Substances, ECETOC Technical report No. 51, Brussels, Belgium, 1993. Organization for Economic Co-operation and Development, Report of the Workshop on Effects Assessment of Chemicals in Sediment, OECD Environment Monographs 60, Paris, France, 1992. D.M. Di Toro, C.S. Zarba, D.J. Hansen, W.J. Berry, R.C. Schwarz, C.E. Cowan, S.P. Pavlou, H.E. Allen, N.A. Thomas, P.R. Paquin, Technical basis of Establishing Sediment Quality Criteria for NonIonic Organic Chemicals Using Equilibrium Partitioning, Environ. Toxicol. Chem. 1991, 10, 1541 – 1583.
[47] T. Aldenberg, W. Slob, Confidence Limits for Hazardous Concentrations Based on Logistically Distributed NOEC Toxicity Data,. Ecotoxicol. Environ. Safety 1993, 25, 48 – 53. [48] C. Wagner, H. Lokke, Estimation of Ecotoxicological Protection Levels from NOEC Toxicity Data, Water Res. 1990, 25, 1237 – 1242. [49] T. Aldenberg, J.S. Jaworska, Uncertainty of the Hazardous Concentration and Fraction Affected for Normal Species Sensitivity Distributions, Ecotoxicol. Environ. Safety 2000, 46, 1 – 18. [50] J. de Bruijn, T. Crommentuijn, C. van Leeuwen, E. van der Plassche, D. Sijm, M. van der Weiden, Environmental Risk Limits in the Netherlands, Part I. Procedure, RIVM report no. 601640001, Bilthoven, The Netherlands, 2000. [51] C.J. van Leeuwen, Ecotoxicological Effects, in Risk Assessment of Chemicals, An Introduction, eds C. J. van Leeuwen and J.L.M. Hermens, Kluwer Academic Publishers, The Netherlands, 1995. [52] J.W. Deneer, Toxicity of Mixtures of Pesticides in Aquatic Systems; Pest. Manag. Sci. 2000, 56, 516 – 520. [53] D. Mackay, A. Fraser, Bioaccumulation of Persistent Organic Chemicals: Mechanisms and Models; Environmental Pollution, in press. [54] European Commission, Technical Notes for Guidance in Support of Directive 98/8/EC of the European Parliament and the Council Concerning the Placing of Biocidal Products on the Market. Principles and Practical Procedures for the Inclusion of Active Substances in Annexes I, IA and IB, Draft Proposal, April 2001.
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8
Wood Preservatives David Aston
8.1
Introduction
Wood preservatives are one of the most diverse areas of use for biocides. Wood and wood based products are used throughout society all around the world. Lumber, heavy construction timbers, poles, piles, and many other wood based products are derived from trees. Timber may be abundant in a country and be a traditional constructional material or it may have to be imported. In this case the material may have a higher value and can be expensive in economic and environmental terms unless used in a responsible way. Wood has numerous beneficial properties, but it is subject to degradation. This chapter considers the protection of wood and wood based products using chemical treatments against biological agencies.. These chemical treatments may kill the attacking biological agency, interrupt its life cycle or make the timber substrate unpalatable to it.
8.2
Biological Degradation
The biological agencies that degrade wood are economically important, many, and varied. They include microbial organisms, fungi, and bacteria. Insects including termites cause considerable damage to timber based commodities around the world. Timber structures in the marine and freshwater environment are also subject to biological attack from marine borer damage. This chapter can only serve as an introduction to the biological deterioration of timber. There have been several texts on wood preservatives and the organisms that cause the biological degradation of timber. These include Cartwright and Findlay (1958) [1], Hunt and G .A. Garrett (1967) [2], D.D. Nicholas (1993) [3], Hickin (1975) [4], The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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8 Wood Preservatives
Findlay (1985)[5], Richardson (1976)[6], Wilkinson (1979) [7], Zabell and Morrell (1992) [8], and most recently Eaton and Hale (1993) [9]. In addition to these sources of information there are also papers presented at the meetings of the International Research Group on Wood Preservation. The Secretariat of this organization can be contacted at IRG Secretariat, Box 5607. S-114 86 Stockholm, Sweden,
[email protected] or www.irg-wp.com. This forum provides opportunity for reporting the latest developments in wood preservation.
8.2.1
Microbial Degradation of Timber
Essentially all of the constituents of wood are utilizable by micro-organisms of one kind or another. Cellulose, hemicellulose, and lignin comprise the main bulk of the wood. These are broken down by enzymes secreted by fungi, bacteria, or protozoa into simple compounds such as sugars. These are absorbed and metabolized by the micro-organism. Some of these are to be found inside larger organism such termites. Some woods are more resistant to microbial degradation, and this resistance is mainly due to the presence of extractives that act as natural preservatives. Fungi attack wood under damp conditions. This decay often originates in wood that is in contact with the ground or where wood becomes damp through poor maintenance or design. It is common to recognize four kinds of microbiological damage, namely decay or rot (brown rot and white rot) * * *
Soft rot; Stain (bluestain in service and sapstain) and moulds; Bacterial degradation.
Brown rots are recognized by a darkening of the wood under attack. On drying the wood becomes brittle and often cracks. Fungi of this type are those commonly causing decay in buildings, e.g. the dry rot fungus Serpula lacrymans and wet rot fungi such as Coniophora puteana. White rots are characterized by a lightening of the attacked wood, especially hardwoods. Fungi of this type are commonly found causing decay in external joinery. Soft rots are characterized by wet wood being softened progressively from the surface. Wood used as in cooling towers or in the ground are prone to this kind of attack and hardwoods are particularly susceptible. Stains and moulds are surface growths that do not change the mechanical properties of the wood but instead discolor and disfigure it. This can result in a loss of value. Whilst some organisms occur widely throughout the world, many more are very specific to particular climatic regions, soils or waters. Bacteria attack wood when it
8.2 Biological Degradation
is extremely wet e.g. when stored in log ponds, buried in the soil, or used in cooling towers.
8.2.2
Insects and the Degradation of Timber
Insects are the second major category of biological organisms that can damage and destroy wood products. The moist conditions that support fungal decay in wood often encourages insect infestations. Examples include powder post beetles (lyctidiae), wood worm (anobiidae), bostrychidae, long-horn beetles (cerambycidae), pinhole borers (scolytidae and platypodidae). Wood can be attacked by insects at any stage in its existence. Some insects only infest bark, many prefer hardwoods to softwoods, and others will only attack wood that has been seasoned. In some species it is the adult that causes the economic damage while in others it is the larvae. Generally speaking in temperate climates fungi cause the greater economic loss whereas in the tropics it is generally insects that cause the greatest loss.
8.2.3
Termites and the Degradation of Timber
Termites (isoptera), subterranean, dampwood, and drywood are social insects that cause significant economical damage. The protection of wood based construction, dwellings, and artifacts made from wood from termite attack requires the application of a number of techniques and processes, including the use of wood preservatives both as preventive and curative measures.
8.2.4
Degradation of Timber in the Marine, Brackish, and Freshwater Environments
In the aquatic environment there are three main categories of marine borers that damage wood in salt or brackish water, namely shipworms, pholads, and gribble. Marine borers are widely distributed throughout the world and are especially active in tropical waters. All molluscan borers are active in tropical waters and only species of teredo are found in cooler waters. Marine piling is particularly affected by the way these borers attack the inside of the piling. The main crustacean species are limnoria and sphaeroma. These species are much smaller and their tunnels cause the wood to look sponge-like.
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Sphaeroma are chiefly found in warm waters, whereas limnoria are more widely distributed.
8.3
Wood Preservatives-Some Characteristics 8.3.1
Categorization by Function
Wood preservatives are used to prevent damage caused by fungi, insects including termites and marine borers. There are other products commonly referred to as “wood protection” products. These are mainly applied as coatings whose prime function is to protect the surface of the timber from physical (abiotic) damage especially photodegradation by ultraviolet (UV) light. These may or may not be placed on the market claiming wood preservative properties. The claims made for the product are all important in the regulatory control of the product. It is now customary to categorize wood preservatives into preventive and curative types. In the case of the “preventive” type these are applied to the wood prior to it going into service. The objective being to prevent or delay biological degradation. For “curative” type products these are applied to wood that is being subject to biological degradation. 8.3.2
Regulation of Wood Preservatives
In most countries of the world wood preservatives are regulated, and an authorization has to be obtained before the wood preservative product can be placed on the market. Generally product authorization regimes categorize the following types of end user, * * *
Amateur (do it yourself); Professional; Industrial.
The products that can be used by each group vary because of the hazard of the active substances in the formulations and the potential for human exposure, as well as environmental considerations.
8.5 Deciding on the Degree of Protection Needed
8.3.3
Desirable Characteristics of Wood Preservatives
In general, wood preservative formulations must: * * * * * * * *
Have sufficient efficacy against the target wood-destroying organisms; Be able to penetrate wood if required; Be chemically stable; Be able to be safely handled; Be economical to use; Not weaken the structural strength of the wood; Not cause significant dimensional changes within the wood, Result in treated wood that does not cause environmental problems.
8.4
Wood Preservation at Various Stages of the Timber Transformation Process
Biological attack is possible during all of the phases of wood processing. Freshly felled trees are liable to attack by insects and fungi due to the high moisture content and the presence of sap in the timber. The use of prophylactic chemical treatments is common at this stage and logs may be sprayed at the logging site with biocides to reduce the attack of valuable timber. Wood is also subject to biological attack and physical damage during seasoning, storage and transportation Surface disfiguring fungi are the main risk but wood destroying fungi and attacks by insects, especially in the tropics, can also significantly reduce the value of the timber in a very short time. Good practices in seasoning, storage and transport can reduce the need for chemical treatments. Finally at the end use stage the durability requirements of the commodity or the construction have to take into account hazard and the likely risk of biological attack.
8.5
Deciding on the Degree of Protection Needed
The choice of preservative depends on the character of the wood, the required service life of the treated wood and the properties of the formulation. The amount and type of protection need for wood products that are potentially subject to attack by rot, insects, marine borers, or termites vary depending on a number of factors. These include:
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8.5.1
The Proposed End Use for the Wood Product
Here the degree of protection required may be to prevent sapstain development in timber during its transit from the sawmill to the next stage in its processing. Or, it may be a utility pole or a framing timber house construction. Some typical end uses of wood (not in order of importance) are poles, railway sleepers, piers, cooling towers, construction timbers, trussed rafters, carcassing, industrial flooring, parquet flooring, carriages, trucks and containers, exterior and interior cladding, mouldings, interior and exterior joinery, indoor and outdoor furniture, roofing shingles, wooden packaging, pallets, greenhouses and silos, stalls, stables and agricultural buildings, toys, playground equipment, wood in food contact. Particulate wood also goes into particle and fiberboard and veneers go into furniture and plywoods.
8.5.2
The Geographical Location in Which It Is Intended To Be Used
The occurrence of biological agencies varies around the world. In many countries fungal decay is the main problem, whilst in others it may be termites.
8.5.3
The Expected Service Life or Degree of Protection Required
The degree of protection required may only be a few weeks or months in the case of sapstain control products, whilst in the case of utility poles and housing the expected service life will be several decades.
8.5.4
Structural or Nonstructural Applications
If wood is intended to be used in a structural application, particularly one where human life could be at risk, the use of properly treated wood in a structure designed with the appropriate safety factors is critical if property damage and injury are to be avoided.
8.5 Deciding on the Degree of Protection Needed
8.5.5
Ease and Economics of Replacement
An important factor to consider when choosing the level of protection needed is the cost of replacing any material that suffers from biological degradation. Costs and problems associated with the removal and replacement of damaged components in timber structures will also point to the need for an enhanced level of protection.
8.5.6
Service Factors
Table 8.1 shows the kind of risk assessment process the specifier or consumer can be guided through in deciding whether or not to use timber treated with a preventive wood preservative. The table derives a Service Factor. This approach, or variations of it, can be found in a number of national and industry standards and codes of practice.
8.5.7
Biological Hazard Classes
The Hazard Class system is a means for defining different in-service environments within which wood and wood based products are used. In practically every major established specification system around the world the concept of in-service “Hazard Class” is used. Hazard classes not only describe the distinct circumstances of the end-use (service conditions) but they also reflect different classes of biological hazards likely to be encountered.
Tab. 8.1.
An example of the derivation of service factors
Safety and economic considerations
Need for preservative treatment/natural durability
Service factors
Negligible
unnecessary
A
Where remedial action or replacement is simple and preservation can be regarded as an insurance against cost of repairs
optional
B
Where remedial action or replacement would be difficult and expensive
desirable
C
Where collapse of structures would constitute a serious danger to persons or property
essential
D
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On this basis timber based commodities can be assigned to a hazard class which in turn defines the preservation requirements necessary to provide adequate resistance to the organism(s) that may be found in that situation (hazard class). In principle, it is internationally accepted that the assignment of a commodity or building component to a particular biological hazard class is complemented by good design, use and maintenance of the construction. In Europe, the CEN (European Standards) approach is defined in EN 335 Part 1 (1992) [10] Classification of Hazard Classes. These Classes are defined as Hazard Class 1 End-use situation in which wood or wood-based product is under cover, fully protected from the weather and not exposed to wetting. Hazard Class 2 End-use situation in which the wood or the wood-based products under cover and fully protected from the weather, but where high environmental humidity can lead to occasional but not persistent wetting. Hazard Class 3 End-use situation in which the wood or the wood-based product is not covered and not in contact with the ground. It is either continually exposed to the weather or is protected from the weather but subject to frequent wetting. Hazard Class 4 End-use situation in which the wood or the wood-based product is in contact with the ground or freshwater, and thus is permanently exposed to wetting. Hazard Class 5 End-use situation in which the wood or wood-based product is permanently exposed to salt water Table 8.2 abstracted from DD 239 (a new British Standard Draft for Development) [11] shows the linkages between Biological Hazard Class, the Component and the Service Factor. This table was prepared for UK situations and practices, however the principles are embodied in CEN standards as well covering European countries.
8.5.8
Use Classes
This concept of Hazard Classes has been further developed in the proposed ISO International Framework for classifying wood products durability based on use classes, based on the Biological Hazard Class. Whilst some of the procedures developed in
8.5 Deciding on the Degree of Protection Needed Tab. 8.2. Abstracted from DD 239 British Standard Draft for Development [11] to be published as BS 8417 Component
Biological Hazard Class
Service Factors
Internal joinery
1
A
Roof timbers dry
1
B
Roof timbers dry (hylotrupes risk)
1
D
Roof timbers (risk of wetting)
2
C
External walls/ground floor joists
2
B/C/D
Sole plates below dpc
4
D
External joinery (nonload bearing)
3
C
Fence rails
3
B/C/D
Fence posts
4
B/C/D
Poles
4
D
Sleepers
4
D
Timbers in fresh water
4
D
Timber in salt water
5
D
Cooling tower packing (fresh water)
4
D
Cooling tower packing (sea water)
5
D
different regions of the world have features in common, distinct differences have evolved often in response to particular local geographical, climatic, or end-use needs. Well-established practices in different regions are often embodied in codes and standard specifications which themselves are either part of or integrated into national or regional regulations. Table 8.3 is taken from a draft ISO standard to show an international Use Classification Guide being prepared by ISO TC/165 SC1 Wood Materials- Durability and Preservation. In each of the different hazard class systems class 1 represents the biologically demanding situation in terms of wetness sufficient to permit fungal decay. Consequently the lower hazard classes (1 and 2 and any sub divisions) generally provide for in-service circumstances where there may be significant risks of attack by some wood boring insects such as lyctids, anobiids, and some genera of termites but little or no fungal hazard. The intermediate hazard class 3 (and any subdivisions) provide for in-service circumstances where timber is out of ground contact, exposed to wetting, and may have varying degrees of protection or shelter. The main biological hazards are decay, some wood boring insects, and termites. The higher hazard classes provide for in-service circumstances in contact with the ground, or with fresh water or salt water. In these classes the biological hazards are diverse and may be extreme.
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Use class guidea
Class
Service Conditions
Typical Uses
Biological Agents insects
A
woodboring beetles
1
interior, dry
framing, roof timbers
insects
B
as A + termites
2
interior, damp
framing, roof timbers
As # 1
A
+ decay
As # 1
B
+ termites
3
4
5
protected exterior
exterior joinery
As # 2 + disfiguring fungi
B unprotected exterior
deck boards
As # 2
A in-ground
fence posts
As # 3 + soft rot
B in-ground, severe, fresh water
cooling towers
As # 3
marine
Piles
As # 4
A
teridinids + limnoria
As # 4
B
creosote tolerant limnoria
As # 4
C
sphaeroma, pholads
a It may not be necessary to protect against all the biological agents listed, as they may not be present or economically important in all geographic regions, in all service conditions.
8.6
Selection and Specification of Preventive Preservative Treatments
Where the required durability of a given timber component is to be achieved by treatment with preservatives, and where it is intended to market treated timber components with a specific level of durability, preservation will need to be appropriate to the particular local recommendations or regulatory requirements. Varying local conditions can lead to different service life expectations for the same commodity or component in different parts of the world, e.g. Findlay(1985) [5] contains contributions on the preservation of timber in the tropics. Currently the procedures for defining particular preservation requirements vary significantly in different geographical regions of the world. Some systems provide specific and prescriptive requirements in terms of wood species, preservative types, treatment process parameters to be followed, loadings and penetrations, and performance; whilst others are less prescriptive and less performance based. Specifications and consumer choice can now be made on a rational basis using these kinds of hazard class systems.
8.8 Wood Durability and Treatability
8.7
Selection and Specification of Curative Preservative Treatments
Curative wood preservative treatments are used to eradicate existing biological attack. Typically they are used in buildings, however the major exception to this is in the remediation of power and telecommunication poles where ground line treatments are carried out to extend the service life the pole. In some countries the application of curative wood preservative products is made following extensive survey work and after other building works have been carried out to prevent re-infestation. For example the removal of water ingress to the building by better rainwater control which had enabled the wood rot to become established. Some of the properties that the specifier and user needs to bear in mind when selecting the product to use include: * * * * * *
Spectrum of activity; Stability of the product in the container; Stability of the solution after freezing; Stability in water; Flash point; Properties of the treated wood; – Corrosion of fittings and fixtures; – Paintability; – Mechanical properties; – Fire resistance.
8.8
Wood Durability and Treatability
Wood from different tree species varies widely in its characteristics especially from the point of view of natural durability. The heartwood of the timber may be naturally durable, however almost without exception the sapwood of all tree species is vulnerable to biological degradation. Some heartwood may also be vulnerable as well. Generally there is a relationship between the treatability of the wood and its vulnerability to biological attack. This has led to the classification of the durability of heartwood and the permeability of the timber (hence its treatability). The durability classes are Perishable, Nondurable, Moderately Durable, Durable and Very Durable. The treatability classes are Permeable, Moderately Resistant, Resistant, and Extremely Resistant. These are the classes used in Europe.
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The terms “hardwood” and “softwood” do not directly describe the hardness or the softness of the wood. Instead this distinction is based on a botanical classification and refers to the leaf form and the mode of seed production. Softwoods are also very strong for their weight compared to hardwoods, and hence timber from softwood species is most commonly used for construction timbers, lumber, poles, piles etc where functionality rather than appearance is important. Wood has a complex structure and the structure is the key in determining the treatability of the timber. Eaton and Hale (1993) [9] describe the structure of wood more fully.
8.9
Methods of Applying Wood Preservatives
There are many ways in which wood preservative products are applied to timber and the description below is by no means complete. Eaton and Hale (1993) give good descriptions of the many and varied techniques used for the application of wood preservatives. 8.9.1
Treatments for Seasoned Wood
Seasoning is the controlled removal of moisture from “wet” or green wood. Seasoned wood usually accepts wood preservatives more easily because there is more space available within the wood structure . Pressure Treatments These are done in purpose built timber treatment installations where the timber is treated under vacuum and pressure in a closed vacuum pressure timber treatment installation. Depending on the actual process used the timber is typically subjected to an initial vacuum following which the vessel (usually a cylinder or autoclave) is filled with preservative solution and pressure, usually hydraulic, applied to it. The amount and the duration of the pressure period depends on the species and the penetration required. At the end of the pressure period the vessel is emptied of preservative solution, and typically a final vacuum is used to recover a proportion of the wood preservative from within the wood cells. This wood preservative solution is recovered back into the system for re-use in the next treatment batch. The process is a closed one. The only processing waste being generated in the removal from the treatment vessel of any sludges produced from sawdust or dirt brought 8.9.1.1
8.9 Methods of Applying Wood Preservatives
into the vessel on the wood to be treated. Wherever possible, deliveries of the wood preservative are made in bulk tankers, or in returnable/recyclable containers. There are many variations of this type of process used throughout the world. Other variations include oscillating and alternating pressure methods and these use repeated cycles of pressure and vacuum during the process. Double vacuum/low pressure processes are also used and here the pressures used are up to one-tenth of those used in pressure processes. Creosote is normally heated to reduce its viscosity before it is applied to the timber in a vacuum pressure process. Computer controlled processing and intensive monitoring of all of these treatment processes are increasingly being used in the industrial treatment industry, further enhancing the production of high quality treated products and the optimization in the use of the wood preservative to meet the required specification. In all of these processes the bark has to be removed prior to treatment because not only does it prevent the penetration of the preservative into the timber but it will also retard the drying of the timber to the point at which optimum treatability is reached. The treatment processes may be national e.g. the AWPA specify minimum vacuum, pressure, penetration and other requirements. On the other hand CEN standards are not concerned with the treatment process itself but require the process to result in the correct penetration and loading of preservative in the analytical zone. Whichever route is used the actual amount of preservative used depends on the hazard class to which the timber will be exposed in service. Nonpressure Methods These include the brushing, spraying, immersion or dipping, and deluging of the wood preservative and the spreading of concentrated wood preservatives formulated as pastes. Spray application usually involves the use of coarse spray nozzles to reduce airborne losses and risk of exposure of the operator to the spray. Log treatments to prevent insect attack or the use of curative/preventive treatments in remedial treatments inside buildings are examples of spray applications. Dip treatments may done in tanks of varying sizes and with differing degrees of complexity in the mechanical handling of the packs of timber. Dip treatments are also carried out where the freshly converted boards are passed through a chain dip into a sapstain control product before being stacked. Sapstain control products may also be applied in deluging machines where the timber passes through a curtain of the preservative and is coated with the product. Wood preservatives are also formulated in the form of solids e.g. fused or pelleted rods. These may be used for the treatment of timber before it is placed in service or as a maintenance or remedial treatment in service. 8.9.1.2
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Typically curative wood preservatives are applied using these techniques. Bandages encapsulating diffusible wood preservatives may be wrapped around the groundline of poles to extend the service life of the pole. 8.9.2
Treatments for Unseasoned Timber
This can include a prophylactic treatment of the freshly felled logs in particular against wood boring insects or staining fungi. Alternatively, or additionally, the converted unseasoned timber may be dipped in an open tank or passed through a shallow tank by chain. In some processes after treatment the timber is stacked and covered for up to 8 weeks for diffusion of the wood preservative to take place into the timber. After this it is uncovered for drying. Boron based products are used in this technique. Sap displacement methods have also been used to treat round unseasoned timbers.
8.10
Types of Wood Preservatives 8.10.1
Introduction
Over the years a large number of chemicals have been used in the preservation of timber. An interesting review of the development of wood preservative formulations can be found in Richardson (1978) [5] and in Eaton and Hale (1993) [9] covering the period up to the writing of their book. In recent years there have been significant changes in wood preservatives formulations, both preventive and remedial. There is often confusion between wood preservatives and wood protection products. Wood preservatives are usually intended to provide long term protection whereas protection products, such as stains, lasures, or water repellents themselves are designed only to protect the surface of the wood and require frequent renewal. It is advantageous to look at the types of wood preservatives from the perspective of those products available to be used in industrial application processes, by professionals (as in the remedial treatment industry) and those products that can be used by the amateur (DIY). Whilst the main function of the wood preservative is to protect the wood against the target biological agencies, formulations have also been developed which give additional properties to the wood preservative product and the resulting treated timber. Examples include water repellency (mixtures of wax, resins or drying oils) and color.
8.10 Types of Wood Preservatives
8.10.2
Industrial Wood Preservatives
For many years inorganic chemical formulations based on copper chromium arsenic (CCA), copper chromium boron (CBC), and copper chromium fluorine (CFK), distillates from coal tar including creosote, and PCP in heavy oil have been the main “heavy duty” preservatives used throughout the world. Today CCA wood preservatives are still the most widely used around the world in terms of the volumes of timber treated. Since their development in 1933 a number of variations of the combination of CCA have been developed and these have customarily been categorized as Types A, B or C. The principal form used today is the Type C and the reason for this is the optimization in the degree of fixation of the active substances in the wood substance and the consequential resistance to leaching with the resultant long term protection of the wood commodity. The use of CBC is now reducing, and the use of CFK is very much reduced. In the last decade alternative products have been introduced into the market, partly as a result of legislative restrictions on the traditional wood preservatives, perceived improved health safety and environmental properties and partly because of new technologies available to the industry. Products such copper formulated with combinations of different azoles, ACQ (ammoniacal copper quats), copper HDO [copper, bis(N-hydroxy-N-nitrosocyclohexanaminato-O,O’)] have all been introduced as alternatives to the traditional inorganic wood preservatives. In some parts of the world, e.g. US, Australia, and South Africa borates are used for the treatment of framing timber in timber framed constructions and where they not likely to be exposed to moisture. Creosote is still an important product used in the protection of utility poles and railways crossovers. There are restrictions on the benzo a pyrene content of the creosote permitted to be used. In the late 1960s the introduction of wood preservatives (LOSP) using light organic solvents, such as petroleum distillate were introduced for building timbers and exterior joinery where the properties of the solvent meant there was a significantly reduced period of time after treatment and when the treated timber could be further processed. The growth and speeding up of joinery production processes also required faster drying treated timber components. A variety of combinations of active substances have been used in these formulations over the years, such as pentachlorophenol (PCP), TBT based compounds, such as tri-nbutyltin oxide and TBT naphthenate, dieldrin, lindane (v HCH), zinc naphthenate, acypetacs zinc, and zinc versatate.
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Today’s LOSP products are formulated around mixtures of azoles such as propiconazole, tebuconazole, azaconazole, IPBC, and where insect protection is required contact insecticides such as permethrin and cypermethrin are used. In the last decade pressures on the use of solvents in terms of controls on volatile organic compounds in the workplace as well as issues around climate change have lead to the substitution of these LOSP for the greater part of the construction timber and roof truss markets, leaving LOSP based formulations principally remaining for the treatment of window and exterior joinery. Even this is changing. Waterbased emulsion formulations using combinations of propiconazole, tebuconazole, IPBC, quaternary ammonium compounds, and contact insecticides such as permethrin and cypermethrin. The critical aspect of these formulations is in their formulation because the combination of the treatment process with high shear forces, and the presence of extractives from timber are severe tests of the robustness of the formulation. The trend in recent years has been to formulate products using combinations of biocides. This has been necessary because none of the active substances currently available to the industry has a complete spectrum of activity across the range of fungal hazards the treated commodity maybe exposed to in service. Active substances, such as PCP could be used on their own because of their wide spectrum of activity. Much more is also known about the processes of microbial colonization of timber in the various hazard classes and this has enabled formulations to be developed utilizing this knowledge. Much of this knowledge is proprietary information and is not disclosed into the public domain. In general the wood preservation industry is dependent on molecules that have been developed in the plant protection market because the size of the wood preservation industry on its own does not economically justify the investment required to develop an active substance and bring it to the market solely for wood preservation. This reliance on the plant protection sector is problematic because in some ways the requirements for the plant protection sector include rapid chemical physical and biological degradation once the pest has been controlled. Whereas for wood preservation, certainly in the use of preventive products, increased permanence of the active substance in the wood is required if the treated commodity is going to perform over the required service life of the product. This may be several decades in very testing environmental conditions. The characteristics of the active substance in the wood exerting its protective effect for the desired service life are considered to be its “permanence”. This should not be confused with “persistence”, that is to say the degradability characteristics of the active substance when released from the timber it is protecting into the environment. Waterborne boron compounds have historically been used for the diffusion treatment of green timber and in recent years there has been renewed interest in their use
8.10 Types of Wood Preservatives
in this case for the treatment of building timbers however the property of mobility in high moisture content situations can be a detracting property. In some countries the treatment of framing timbers with boron based wood preservatives is common practice. Aqueous solutions of pentachlorophenol have been used in the control of sapstain and mould fungi, but today the use of this material is restricted and other products based on quaternary ammonium compounds, 2(thiocyanomethylthiobenzothiazole), and substances such as 3-iodo-2-propynyl-N-butyl carbamate (IPBC) are used. Copper8-hydroxyquinolinolate (oxine copper) is also used for this purpose. 8.10.3
Remedial (Professional), Curative and Preventive Wood Preservatives
In the case of remedial treatment products they may be curative and curative/preventive in action. In other words in the curative situation they may be applied to control an existing infestation whilst after this control has been carried out there may be a need to have a product that is preventive in function and is there in case the infestation should reoccur. Deep penetration is required when large cross sections of timber are involved and bodied mayonnaise-type emulsion products may be used. These are pastes applied to the surface of the wood by trowel or gun, the emulsion breaking on contact with the wood enabling the solvent to carry the active substance into the wood. Injectors may be used to inject the wood preservative formulation into the timber using either solvent based or today more usually water based emulsion. Insecticidal smokes are another method of delivery. Today lindane has been replaced by synthetic pyrethroids. Fumigants such as methyl bromide are very restricted in where they can be applied. Bandage or ground line treatments have been carried out as remedial treatments to extend the service life of utility poles. These involve the application of products that will diffuse into the pole, such as boron and fluorine, either directly or impregnated into a bandage which is wrapped around the pole. The pole and bandage is then wrapped in an outer wrapping of polyethylene film. 8.10.4
Amateur/Do It Yourself Wood Preservatives
For amateur products there is increasing pressure to restrict creosote (carbolineum) products and long established materials such as copper naphthenate are increasingly restricted.
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Acypetacs zinc, permethrin, and IPBC (in both aqueous and solvent based formulations) have been developed. Copper naphthenate and zinc naphthenate are no longer available in some countries despite a long history of use by amateurs. Alkyl ammonium compounds and dichlofluanid are also used in amateur products.
8.10.5
Listing of Active Substances Currently Registered for Use in Wood Preservatives in the UK
The following list of active substances cleared for use in wood preservatives has been compiled from the UK Pesticides 2001 [12] publication issued by the UK Health and Safety Executive and the Pesticide Safety Directorate. Acypetacs copper/acypetacs zinc/alkylaryltrimethyl ammonium chloride Alkyltrimethyl ammonium chloride/ammonium bifluoride/arsenic pentoxide Azaconazole Benzalkonium chloride/benzalkonium bromide/boric acid Carbendazim/5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4-isothiazolin-3-one/ coal tar Creosote/chromium trioxide/copper carbonate/copper oxide Copper naphthenate/copper sulfate/cyfluthrin/cypermethrin Deltamethrin/dialkyldimethyl ammonium chloride/dichlofluanid/disodium octaborate/disodium tetraborate/dodecylamine lactate/dodecylamine salicylate Flufenoxuron 3-Iodo-2-propnyl-N-butyl carbamate Lindane Methylenebis(thiocyanate)/2-(thiocyanomethylthio)benzothiazole Oxine-copper Pentachlorophenol/pentachlorophenyl laurate/permethrin/2-phenylphenol Pirimiphos-methyl/potassium dichromate/propiconazole Sodium 2,46-trichlorophenoxide/sodium 2-phenylphenoxide/sodium dichromate Sodium fluoride/sodium pentachlorophenoxide/sodium tetraborate Tebuconazole/tri(hexyleneglycol)biborate/tributyltin naphthenate/tributyltin oxide Zinc naphthenate/zinc octoate/zinc versatate This listing covers those active substances used in the UK to formulate wood preservatives.
8.10.6
European Chemicals Bureau
The European Chemicals Bureau now maintains a comprehensive listing of the active substances used in wood preservatives in the Member States of the European Union as at 15 May 2000. It is accessible on their website.
8.11 Wood Preservative Systems
8.11
Wood Preservative Systems 8.11.1
Introduction
Another way of describing wood preservatives is to look at them in terms of systems. Most wood preservative products are mixtures of active substances selected to give the required spectrum of activity. The activity of the active substance can be heavily influenced by the formulation chemistry of the product.
8.11.2
Industrial
For preventive wood preservative products the following systems are in use throughout the world. There is no significance in the order of the listing. Acid Copper chromate (ACC) Ammoniacal copper arsenate (ACA) Ammoniacal copper zinc arsenate (ACZA) Copper azole Chromated copper arsenate (CCA) Copper chrome boron (CBC) Copper HDO Chromated zinc chloride Quaternary ammonium compounds Inorganic boron Disodium octaborate tetrahydrate Borate rods Glycol solutions containing borates Ammoniacal copper carboxylate (e.g. caprylic acid) Ammonical copper alkylammonium compounds (ACQ) Copper quats (ammoniacal copper/didecyldimethylammonium chloride) Ammoniacal copper dithiocarbamate (CDDC) Ammonical copper citrate Bis(N-cyclohexyldiazenium-oxy)copper (CuHDO) Polymeric betains Substituted isothiazolines Chlorothalonil Creosote Triazoles Carbamates Thiazoles Copper naphthenate
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8.11.3
Remedial
Remedial treatments these may be applied as pastes, bandages, fumigants, liquids for internal treatment or solid rods. Actives used include: Pentachlorophenol, creosote greases, fluorides, and dichromates; Fumigants such as trichloronitromethane, sodium methyldithiocarbamate, methylisothiocyanate; liquid formulations containing fluorides, borates, pentachlorophenol, dichromates, copper naphthenate, arsenates, alkyl ammonium compounds, permethrin and cypermethrin; solid rods containing borates or fluorides are used.
8.11.4
Amateur
These products are usually supplied in a liquid form so they can be applied by brushing or dipping. Solid rods are also available to the amateur user. Actives used include dichlofluanid, disodium octaborate, zinc octoate, IPBC, propiconazole, tributyltin naphthenate, permethrin, and alfa cypermethrin.
8.12
Usage Rates
In the case of remedial treatment and amateur products (curative and preventive) usage rates are expressed in gms m-2 of wood surface to be treated. For wood preservatives (preventive) that are applied by vacuum pressure techniques it is custom and practice to express the usage rate in terms of the weight of wood preservative (expressed as the concentrate or ready to use product as supplied) and the volume of the timber into which the wood preservative has been applied, for example kg m–3 or lb cu ft–1. This is calculated on the amount of wood preservative used in the volume treated in each charge (batch) in the treatment plant. It does not necessarily mean each piece of timber contains the same amount of wood preservative. Generally the process is optimized to achieve the desired penetration and retention of the product in the sapwood, this being the part of timber most vulnerable to biological degradation. The proportion of sapwood in a batch of timber pieces varies considerably and may vary within the single piece of wood. Confusion does arise when data are compared. In Europe, for example, CEN Standards now require the usage rate to be
8.13 Disposal of Wood Commodities Containing Treated Wood and Environmental Risk
expressed in terms of the amount of product to be found in the “analytical zone” (which varies according to the biological hazard class). This analytical zone defines the penetration and the retention of the wood preservative to be found in it. The analytical zone for hazard classes 4 and 5 for example require full sapwood penetration whilst they are different for the other hazard classes. Details on the expression of retentions and the analytical zone can be found in EN 351-1 (1996) [13]. In practice treatment plants processes will be set up to operate on standard processes. These processes having determined a safe relationship between the process variables and meeting requirements in terms of the analytical zone, penetration, and retention of the wood preservative.
8.13
Disposal of Wood Commodities Containing Treated Wood and Environmental Risk
In many countries the option of land filling of waste is either very restricted or there may be limited or no landfill sites available. Treated wood should not be burned in open fires such as barbecues, fireplaces, or stoves. Redundant treated timber will increasingly either be recycled into a secondary use or converted into or incinerated as a co-fuel with other waste streams. The incineration of redundant treated timber has been well studied, and whilst technically it is possible to incinerate treated timber and recover the inorganic components it is the practical and economic problem of bringing to a central processing point that so far has only resulted in limited progress being made. Apart from potential confusion arising when assessing and comparing the relative performance of different wood preservatives this lack of understanding on how the industry expresses usage rates can lead to erroneous conclusions being drawn when environmental risk assessments are performed about the quantity of treated wood that may require disposal. The wood preservative is predominately in the sapwood of the timber and the proportion of sapwood in the timber is very variable, ranging from 100 % to 1 or 2 %. Because of this, significant overestimations in the actual amount of treated wood can be made. The same problem arises when estimations are made of losses of wood preservatives from treated wood after a period of time in service using the overall charge retention figures for product usage as the initial amount of wood preservative in the wood. This assumes every piece of treated wood has been treated to the same retention and each piece is uniform in its penetration characteristics. In practice this rarely occurs. Subsequent analysis of the timber after it has been in service may show high levels of depletion and whilst these losses may be real it may well be that the comparison of retentions made before and after service is a flawed one because of this complica-
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tion. Especially crucial is the use of the same sampling regime at each time of sampling. Regrettably many papers published on the depletion of wood preservatives in service and the subsequent environmental risk assessments carried out are open to these criticisms.
8.14
Mechanisms of Action
Paulus (1993) [14] details the modes of actions of a number of microbiocides. Corbett et al. (1984) [15] also extensively reviewed the mode of action of a number of biocides.
8.14.1
Microbiocides
Creosote: The composition of Creosote varies throughout the world. Its composition is extremely complex with over 200 different compounds having been identified in it. These include: * * *
Tar oils – e.g. phenol, cresol, xylenol; Tar bases – e.g. pyridine, quinoline, acidine; “Neutral” oils – mixtures of naphthalene, anthracene, and other neutral hydrocarbons.
Phenols are known to combine with cell membranes of the micro-organisms and to react with essential metabolites e.g. causing protein denaturation. Solubilization of the membrane lipids and disruption of the membrane is one of the mechanisms of action. Heterocyclic nitrogen compounds are essential for life, but synthetic sources can interfere with normal metabolic processes such as growth and membrane transport. Some of the protective effect given to timber by creosote may be due to the hydrophobic components of creosote. Orthophenylphenol: This is an membrane active biocide, it penetrates the cell wall and the cell. It reacts with the cellular protein and also inhibits enzyme action, e.g. oxido-reductases and the enzymes of carbohydrate and protein synthesis are particularly sensitive. Furmecylcox(carboximide): Known to affect electron transport (Kuhn 1984) [16].
8.14 Mechanisms of Action
Pentachlorophenol: It is known to uncouple oxidative phosphorylation. Copper compounds: The Cu2+ cupric ion interferes with the activity of the pyruvate dehydrogenase system inhibiting the conversion of pyruvate to acetyl CoA within mitochondria. Copper naphthenate: Copper reacts with most essential components in the cell. It also reacts with ligands on the cell surface and this can interfere with membrane function. Chromated copper arsenate (CCA)/ammoniacal copper arsenite (ACA): Here the copper act extracellularly (i.e. inhibit the production of extracellular enzymes). The fungus may cause mobilization of the copper and its solubilization causes it to penetrate the cell and react with essential cell constituents. Heavy metals may have to penetrate the cell wall for their toxic effect to be expressed. Carriers are needed to transport the heavy metals. Once inside the cell they compete with magnesium, calcium and potassium ions for receptor sites, they inhibit enzymes and cause the nonspecific precipitation of proteins. Arsenic: Arsenate ions act by uncoupling oxidative phosphorylation and substrate level phosphorylation, c.f. arsenite ions inhibit a-ketoglutarate dehydrogenase in the TCA cycle and or the pyruvate dehydrogenase complex. Boric acid: (this may be generated from a number of boron compounds) This is known to inhibit enzymes, e.g. blocking enzymes involved in the metabolism of phosphate. Stable complexes are formed with important biological molecules. Azoles (triazole type): Examples of these are azaconazole, propiconazole and tebuconazole. They act by blocking the biosynthesis of ergosterol that is the main sterol in many fungal species. They prevent the conversion of lanosterol to ergosterol. Specifically they inhibit the enzyme C14 demethylase which causes the demethylation of lanosterol. Carbamates: These are fungitoxic metal binding agents e.g. IPBC , carbendazim methyl-N- benzimidazol-2-ylcarbamate. Alkylene bis-dithiocarbamates have a nonspecific mode of action.
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Dialkyldithiocarbamates inhibit pyruvate dehydrogenase and a-ketoglutarate and succinate dehydrogenases Isothiazolones: These react with nucleophilic cell entities, thus exerting antimicrobial activity. They also specifically inhibit flavoenzymes in the Tri Carboxylic Acid cycle. TCMTB 2-(thiocyanomethylthio)benzothiazole N-Haloalkylthio compounds e.g. dichlofluanid, tolylfluanid The N–S bond has the capacity to open up and react with the nucleophilic components of the microbial cell Quaternary ammonium compounds: These are surface active agents and their mode of action is extremely complex. In the case of Benzalkonium chloride the point of attack is the microbial cell membrane. Interference of the mitochondrial membrane and function Trihexyleneglycolbiborate this is used in remedial treatments and hydrolyses to boric acid Bis(tri-n-butyltin) oxide (TBTO) This is an electrophilic active microbiocide e.g. inhibits oxidative phosphorylation.
8.14.2
Insecticides
As already described timber in service may be at risk from attack by a wide range of insects and termites. As well as the need to protect the timber commodity from fungi there may be the need to extend the efficacy of the wood preservative to include insects. A number of insecticides are used in the wood preservation industry, and they may be used in industrial, professional, and amateur products. Some of the active substances listed under fungicides may also have an insecticidal action, e.g. copper. Insecticides with respect to wood preservation can be categorized into those that are “Stomach acting insecticides” such as boron and arsenic. The active component must be ingested by the insect, especially in the boring phases of the life cycle. The insects may rely on the intestinal symbionts e.g. bacteria. The active component may therefore control these symbionts causing the insect to starve. Alternatively there may be direct action affecting the insect’s neural system or affecting life processes in all cells. Another categorization is of “contact acting” insecticides. These usually act on the central nervous system of the insect, discourage the female to lay eggs or interfere with the moulting behavior of the larvae.
8.14 Mechanisms of Action
Historically cyclodiene organochlorine insectides such as chlordane, DDT, endosulfan, heptachlor have been used in some products. The related organochlorine lindane causes excessive release of acetylcholine Organophosphorus insectides such as chlorpyrifos and fenitrothion have also been used. These inhibit the action of acetylcholinesterase. Carbamates e.g. propoxur inhibit acetylcholinesterase activity at the synapse The main product types used in the wood preservation industry are the synthetic pyrethroids such as permethrin, cyfluthrin, cypermethrin, and deltamethrin. All of these act on the central nervous system as well as having some ovicidal effects. They interfere with axonal transmission, in particular the movement of Na+ ions across axon membranes. These may be formulated in a variety of organic solvents and also in water based micro-emulsion formulations. A more recent type of insecticide, the phenylpyrazoles, that acts against the central nervous system, the phenylpyrazoles, act by inhibiting the action of gamma amino butyric acid which is connected with the regulation of chlorine. Death is also by hyperexcitation as with the synthetic pyrethroids. More recently insecticides have been developed that act a molt inhibitors, and they interfere with the action of chitin polymerase in the biosynthesis of chitin. Flufenoxuron is an example. Analogues of the Juvenile Hormone have also been developed, such as Fenoxycarb, and this has both ovicidal and pupation effects. The last group of insect growth regulators are the ecdysone mimics. Insecticides such as Tebufenocide interfere with the insect molting hormone, Ecdysone thus disrupting the life cycle of the insect. Pallaske (1977) [17] outlines the modes of action for Insect Growth Regulators. In Europe a draft standard, pr EN 14128:2001 [18], curative products containing insecticides has been recently issued for public comment. This draft standard categorizes the performance criteria for these products as follows: *
* *
Fast Acting where the required level of effectiveness is reached within 3 months as determined by an appropriate standard test method. Slow Acting where the time period is more than 3 months but less than 1 year. Deferred effect where the product is not designed to have an immediate effect on the target organism but where it is designed to act at a later stage in the life cycle, for example at the time of emergence from the wood.
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8.15
Efficacy Assessment of Wood Preservatives
It can be said that throughout the world the degree of sophistication and extent of testing wood preservatives for their efficacy is extremely well developed and without parallel in the biocides industry. Because wood preservatives must protect the timber against a wide variety of biological organisms, depending on where the treated timber is to be used for periods which may be up to several decades, the process for developing a new wood preservative is considerably more involved and time consuming than is the case for many agrochemical pesticides. There are suites of laboratory based tests to determine the efficacy of the candidate active substance or wood preservative product against the wide range of biological hazards, be they fungal or insect, against which a claim for performance is being evaluated. In most situations these laboratory based tests are deliberately designed to be rapid and accelerated procedures either to act as screening new biocides for their potential as wood preservatives or for establishing the likely usage rate. These laboratory screening tests are then followed up by extensive field trials using e.g. stakes or lap joints in field test sites. These sites may also be selected because the local conditions cause the acceleration of the likely process of decay or where evaluations can be carried out using typical treated timber commodities exposed in the realistic in service conditions. Reliance on laboratory based efficacy testing is no guarantee of performance in the field and in service. The development of so called “designer products” formulated to pass these laboratory based tests without field testing can be fraught with risk. Adequate field testing of a wood preservative takes a minimum of 5 years and it is important to understand that this testing is necessary if the product is to be used to protect a timber commodity intended to last several decades, or it is in a safety critical application or where premature failure may cause significant financial loss. However with the pressure to introduce new products into the market place as soon as possible and the tendency for the regulatory authorities to rely on laboratory tests in setting usage rates, using tests that were principally intended to perform a screening function, entails risk and this risk must be acknowledged by all involved in the regulation and use of wood preservatives and treated timber commodities. It is the industry that bears the greatest risk both financially and through loss of reputation.
8.16 Looking Ahead
8.16
Looking Ahead
Wood preservatives have been regulated for many years and together with the regulation to place products on the market there has been extensive development and experience in the use of national and international standards. These standards have promoted the use of wood preservatives and the perceived benefits of increasing the uses where wood and wood based products can be used. After all wood is one of man’s few renewable resources. Because of this extensive experience the wood preservation sector has been used as the pilot product type in a number of regulatory and environmental developments of legislation. Regrettably this can give misleading impressions that the industry has not performed adequately. On the contrary the industry has consistently taken a pro-active stance in engaging with regulators and other stakeholders in the development of legislation and the derivation of good risk assessment techniques. It is committed to a continual improvement process. There are changes in the market place, as there always have been, and there will be changes in the active substances used by the industry. Industry has to try to make sure that such changes are made on good scientific, technical and well informed grounds in order to ensure continuing confidence in the use of its products and technology for the sustainable use of timber based products.
References [1] K. St.G Cartwright, W.P.K. Findlay, Decay of Timber and Its Prevention, 2nd edition, Academic Press, London, 1958. [2] G.M. Hunt, G.A. Garrett, Wood Preservation, 3rd edition, McGraw-Hill, New York, 1967. [3] D.D. Nicholas, Wood Deterioration and Its Prevention by Preservative Treatments, Vol. 1 Degradation and Protection of Timber, Syracuse University Press, USA, 1973. [4] N.E Hickin, The Insect Factor in Wood Decay, 3rd edition, Associated Business Programmes, London, 1975. [5] W.P.K Findlay, Preservation in the Tropics, eds M. Nijhoff and W. Junk, Dordrecht, 1985. [6] B. Richardson, Wood Preservation, The Construction Press, UK, 1978. [7] J.G.Wilkinson, Industrial Timber Preservation, Associated Business Press, London, 1979.
References [8] R.A. Zabell, J.J.Morell, Wood Microbiology; Decay and Its Prevention, Academic Press, London and New York, 1992. [9] R.A. Eaton, M.D.C Hale, Wood Decay, Pest and Protection, Chapman and Hall, London, 1993. [10] EN 335-1 (1992), Hazard Classes of Wood and Wood Based Products against Biological Attack. Part 1: Classification of Hazard Classes. [11] DD 239 (1998) Recommendations for Preservation of Timber. Draft for Development, British Standards Institution. [12] Pesticides (2001). Your Guide to Approved Pesticides, The Stationery Office London, 2001. [13] EN 351-1 (1996) Durability of Wood and Wood Based Products-Preservative Treated Solid Wood. Part 1: Classification of Preservation Penetration and Retention.
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8 Wood Preservatives [14] W. Paulus, Microbiocides for the Protection of Materials, Chapman and Hall, London, 1993. [15] J.R. Corbett, K. Wright, A.C. Baillie, The Biochemical Mode of Action of Pesticides, 2nd edition, Academic Press, London, 1984. [16] P.J. Kuhn, Mode of Action of Carboxamides, in Mode of Action of Antifungal Agents, eds A.P.J. Trinci and J.F. Ryley, Cambridge University Press, UK, 1984, pp.155-183.
[17] M. Pallaske, Insect growth Regulators: Modes of Action and Mode of Action Dependent Peculiarities in the Valuation of the Efficacy for Their Use in Wood Preservation. International Research Group on Wood Preservation, IRG/WP 97-30155, 1977. [18] prEN 14128 CEN (2001), Durability of Wood and Wood Based Products-Performance Criteria for Products for Curative Uses against Wood Destroying Organisms as Determined by Biological Tests.
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Slimicides Ian Gould and James Hingston
9.1
Microbiological Problems Associated with the Papermaking Process
One of the most troublesome problems faced by papermakers is the uncontrolled proliferation of microbes in their systems. The effects of microbial growth are felt in many areas of the mill and, if left unattended, can totally disrupt economical paper production [1]. A paper mill, as designed, and the papermaking process itself encourage microbiological problems by providing all the necessities of life for microbes. Micro-organisms are introduced in a variety of ways and their presence is rapidly seen. To establish themselves and grow, microbes require water, several essential ions, a source of carbon, nitrogen, and phosphorus, and a favorable environment [2]. The most critical environmental factors are pH and temperature, and some microbes require oxygen. Regardless of its source, most waters used in papermaking contain abundant sources of the essential ions required by microbes in the form of dissolved salts or other impurities. This water is used to carry the pulp fibers through the entire process dissolving natural carbon sources, such as carbohydrates, proteins, and fatty acids, from the fibers along the way. The water is also used to prepare such additives as fillers, size, starches and pigments, which can provide additional carbon, nitrogen, phosphates and essential ions to the process water. As paper mills reuse more water, the ever-increasing organic load causes an ever-increasing microbial population to be recycled with the water and fiber. Most chemically treated pulp entering the system contributes very little microbial contamination, because the pulping process allows few micro-organisms to survive. The primary sources of contamination are other sources of pulp including recycled fiber and waste paper, chemicals and additives used and most of all, the water itself. As the micro-organisms grow, they form slime deposits, which can be felt on surfaces or seen, especially when hanging from the machine structure. When large enThe Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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ough, deposits can be dislodged and show up in the formed sheet as spots, holes, or tears. Breaks in the sheet will interrupt production causing costly downtime. Defects in the finished sheet will result in the production being downgraded to a lower quality or requiring it to be reprocessed through the broke system. The microbes can also impart undesirable properties to the finished product, such as unacceptably high spore counts or offensive odors. Microbial growth in the additives may result in improper sizing or finish, or off-color paper. Micro-organisms can also greatly accelerate the corrosion of metal surfaces and parts, leading to premature replacement of a variety of expensive equipment. The most common forms of micro-organism found in the pulp and papermaking process are briefly discussed in the following sections. 9.2
Bacteria
Bacteria are by far the most numerous microbes that are found in mill systems. Bacteria are single cell organisms with simple growth requirements, exceedingly fast growth rates and enormous powers of adaptability and survival. The outermost structure of most bacteria is a rigid cell wall, although some species secrete gelatinous capsules or slime layers outside the cell wall. Inside the cell wall is a cell membrane that provides a permeable barrier for the cell. Bacteria are able, because of the membrane to concentrate nutrients inside the cell very quickly. Some bacteria can produce spores, which are a resistant form of the cell able to withstand adverse environmental conditions. Since only one spore is formed per cell, the structure is a means of survival for the cell rather than a means of reproduction. When a dormant spore finds favorable conditions, it can germinate, and its growth results in the reestablishment of the vegetative cell form. Some spores are resistant enough, when contained in a formed paper sheet, to pass through the dryer section of the machine and remain viable. These spores may germinate in the paper sometime later and then be responsible for undesirable changes and odors in the paper. In particular this is of concern in the manufacture of grades of paper or board that have a limit on the microbial content of the finished product, such as liquid packaging board. Many rod-shaped bacteria possess flagella, long whip-like appendages to the cell that provide the cell with a means of locomotion. This capacity for motility allows the cell to avoid unfavorable environments and seek beneficial ones. Bacteria require uncomplicated sources of food and energy for growth. Simple sugars often provide all the carbon and energy necessary and inorganic forms of nitrogen may be sufficient. More specialized autotrophic bacteria may get all their energy for growth by oxidation or reduction of inorganic chemicals such as sulfate, sulfide, or
9.3 Fungi
nitrate, but most heterotrophic bacteria do not carry out these reactions. Instead the chemical energy of nutrients is extracted and used by a series of oxidation-reduction reactions in the cell. In aerobic bacteria the ultimate oxidizing agent is oxygen. Anaerobic bacteria, on the other hand, use other electron donors as the terminal oxidizing agent and oxygen may even be toxic to some anaerobes. Facultative anaerobes are not inhibited or killed by oxygen but use it for aerobic respiration when it is available. The anaerobes are less efficient than the aerobes in completely oxidizing substrate to compounds that are corrosive to metals or have offensive odors. Not all types of bacteria occur in paper mills systems and of those that do, only a few types cause problems. Slime-forming bacteria belong to many species, but all either have a discrete, well-defined capsule or sheath surrounding them or secrete diffuse masses of polysaccharide or protein slime. Both slime-forming and spore-forming bacteria grow aerobically or anaerobically. Many strictly anaerobic bacteria can be found in paper mills also, but their roles are often obscure; their microscopic appearance gives no clue to their identities. Sulfate-reducing bacteria are often found in paper mills and are strongly implicated in corrosion problems. Occasionally, filamentous iron or sulfur bacteria also appear in paper mills. Their significance or role in the mill is of concern, since they are also often associated with corrosion. Slime-forming bacteria, spore-formers, sulfate-reducers, anaerobes, filamentous iron, and sulfur bacteria all have a common source of introduction into a paper mill: the water supply. When recycled white water or wastewater is used for makeup or dilution of the fresh water supply, a higher number of organisms are contained in the water supply. Wastewater can be a particularly rich source of bacteria, especially anaerobes and sulfate-reducers. All these recycled microbes have had the advantage of surviving and multiplying somewhere in the system so the period of adaptation is reduced or eliminated, compared to the organisms in the fresh water supply. Other sources of bacterial contamination are the recovered fiber, broke, or purchased pulp, as well as the many additives and treatments used.
9.3
Fungi
Fungi found in paper mills are generally of two broad categories: moulds and yeast. Compared to bacteria, fungi are larger, more complicated and more specialized microorganisms. Most fungi are aerobic, prefer acidic environments and have a wide range of growth temperature. Moulds are readily recognizable as the fluffy, cottony types of growth found on bread or decaying food, often forming highly colored colonies. Microscopically, moulds are
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composed of long filaments or hyphae. The hyphae are composed of groups of cells arranged end-to-end and have rigid cell walls. The hyphae may or may not be separated by cross walls or septa. Inside the hyphae may be discerned nuclei and other specialized organelles. As the hyphae grow by extension of the hyphal tip, they form an intertwined mat known as a mycelium. Both septated and nonseptated hyphae may exhibit branching growth and may form masses of either sexual or asexual spores. Each mould spore can germinate under appropriate conditions to form hyphae and new mycelia. Thus, the mould spore is a means of reproduction and dissemination, in contrast to the bacterial spore. A mould may be reproduced and disseminated by fragmenting the hyphae, as the individual hyphal fragments can also grow. The familiar colored cottony colonies seen are mycelia covered with spores. Spores are responsible for some characteristic colors that moulds often assume, such as black, green, brown, white, or orange. The macroscopic and microscopic appearances, as well as their sexual life cycles, are quite useful in identifying and classifying moulds. Yeasts, like bacteria but in contrast to moulds, show predominantly single-cell forms, although a few have hyphal-type structures. Yeasts differ from bacteria in that they generally reproduce by budding, rather than by fission. To complicate things slightly, yeasts also have sexual cycles and spores, but they can be treated generally as though budding were the prevalent mode of reproduction. Yeasts have rigid cell walls overlaying a cell membrane. The growth requirements of moulds and yeasts are similar to bacteria, perhaps more simple because they are generally degradative feeders, not synthetic ones. Familiar substrates for yeast and moulds in paper mills are cellulose and protein as well as other components of wood fibers. These micro-organisms do not multiply as rapidly as bacteria, but because of their much larger size, carry out very active metabolism. A yeast cell, for instance, may have as much as 50 times the mass of a bacterial cell. Therefore, relatively fewer yeast cells can cause slime problems. In spite of their differences with bacteria, moulds, and yeasts face a similarly hostile environment in a paper mill and use similar means to survive and multiply. They compete directly with bacteria for the limited nutrients available. They capitalize on their distinct growth advantage at acid pH levels, outgrowing many bacterial forms in acid environments. Out of the thousands of species of moulds and yeasts known, relatively few are commonly found in paper mill systems. The sources of moulds and yeasts are the same as the sources of bacteria, including wastewater and recycled water.
9.5 Cooling Towers
9.4
Algae
The least prevalent microbes that are found in paper mill systems are algae. Many forms of algae exist in fresh water supplies: green, blue-green, single-celled, colonial, filamentous diatoms. These all share the characteristic of getting their carbon and energy principally from photosynthesis. They have no particular advantage in paper mills because of lack of sunlight and so do not thrive in mill systems. They may, however, enter the mill in large numbers after multiplying, either in the fresh water or in the reused wastewater.
9.5
Cooling Towers
Another area where the application of slimicides is important in the industrial sector is their use in cooling towers. There are numerous problems specifically associated with microbial growth in cooling tower systems. In addition to their role in promoting corrosion through the production of acidic metabolites, the formation of slime deposits on heat exchange surfaces has been recognized as important in reducing heat transfer efficiency in cooling water systems. The surface properties of bio-films outlined earlier may in fact result in insulating properties that far exceed those of scale or corrosion deposits of equivalent thickness [3]. Modern cooling tower fill incorporating a honeycomb design may form an ideal substrate for growth of slime-forming bacteria and algae, and microbial growth may result in blockages that interfere with water flow, further reducing operating efficiency [4]. In addition to the slime- and spore-forming microbes which are difficult to control due to the protective effect of the polysaccharide sheaths, organisms capable of metabolizing cellulose or lignin are of particular concern in cooling towers containing large volumes of wooden packing material [5]. The presence of these organisms may even lead to the collapse of cooling towers unless adequate biological control measures are undertaken. Finally, organic fouling also presents an inevitable health hazard, with the presence of legionella, and the protozoa capable of harboring this bacterium a particular problem in the waters of cooling towers [6].
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9.6
Control of Microbial Slimes and Deposits
Many varied strategies are used to prevent or remove slime deposits, but all contain common considerations. It is necessary to determine the source, extent and cause of the deposit before a rational decision on how and where to treat the system may be made. A microscopic examination of the deposit will reveal what microbial types are in the slime. Cultural examination of the deposits and process water can confirm or identify the organisms present. Knowledge of which organisms are predominant can then be used to trace the origin of the deposits and may be useful in choosing a biocide program. Determining the source of the responsible microbes can be useful in solving deposit problems. If a deposit contains filamentous iron or sulfur bacteria, for instance, a microscopic examination will quickly identify them. These bacteria are common to both surface and well water supplies and their presence in the mill can usually be traced to improperly treated fresh water sources. The presence of fungi in a deposit may lead to uncovering the source of the fungal contamination and treating that may be more fruitful than attempting to treat the whole mill system. Having diagnosed the cause of the problem and formed some opinions of its source, it is then possible to consider treatment. If biocide treatment seems advisable, the relative effectiveness of the available biocides can be determined in laboratory evaluations of their abilities to kill or inhibit the microbes in the deposit and the process waters [7, 8]. Since most routine biocide evaluations are performed as time-contact tests in a static system, it is important that the test reflect the mill system treated. Evaluations should be run on the water to be treated, so that the variables which can affect biocide performance, such as pH or the presence of other chemicals which might be incompatible with the proposed treatment, will be part of the test. A properly run evaluation will give very useful information on selecting the appropriate biocide, as the activity of the selected biocide can be used to decide how often and at what concentration the biocide should be dosed. Knowledge of the system, its flows and the sources of infection will determine where the biocide should be fed.
9.7
Biocides and Their Activity
Many different biocides are available for use in paper mill systems and understanding their modes of action against microbes often provides keys to their successful use. Some compounds have a very broad spectrum of antimicrobial activity, efficiently controlling bacteria, moulds, yeast; and algae. Others have a narrow spectrum and
9.7 Biocides and Their Activity
are particularly good against bacteria or fungi, but not both. A narrow spectrum product can be very useful when the exact cause of the problem is known. Biocides differ also in whether they kill microbes or simply inhibit them. The term biocide implies kill, but some compounds are really biostats. Even a biostat can be effective in microbial control by keeping the population from multiplying and the constant flow through a mill system will wash out the unattached microbes present while inhibiting the growth of slime deposits. Some compounds are biostats at low concentrations and biocides at high concentration. All microbes that are found in paper mill systems share certain biological characteristics. Primary among these is the necessity of extracting energy from the nutrients in their environment and converting this energy into useful activities that maintain cell integrity. Any chemical that disrupts the orderly extraction and utilization of energy by cells will result in their eventual death. Many biocides commonly used have precisely this function to interfere at some steps in energy metabolism. The cell membrane of all microbes also plays a fundamental role in maintaining cell integrity. Any chemical that disrupts the cell membrane disrupts the permeability barrier of the cell and allows chemical penetration into and leakage out of the cell. Surface-active chemicals, especially quaternary ammonium compounds are cell membrane disrupting chemicals and thus are used as biocides. It can also be shown that surface-active chemicals will enhance the penetration of other toxic molecules into the cell. A quaternary ammonium compound can thus greatly amplify the effect of an energy metabolism inhibitor by increasing the intracellular concentration of the inhibitor. Blending of biocide actives can also expand the spectrum of activity of biocides. Combining an active whose spectrum of activity is narrow with another whose spectrum is different may result in a broad spectrum of treatment. Thus, there exist a large body of experience and a large number of reliable methods for evaluating the effectiveness of biocides in paper mill systems. These can range from simply looking at and feeling surfaces to complex chemical and microbiological analyses. Modern methods of analysis can provide very precise quantitative biochemical and microbiological data on many fouling problems and their control, and should be used to guide the application of biocides in an economical and responsible fashion. 9.7.1
Examples of Biocidal Active Ingredients
The following list of biocidal active ingredients illustrates the relatively wide range of chemical types that have been utilized in slimicide formulations [9]. Traditional biological control has used biocides such as gaseous or liquid chlorine most commonly in cooling towers and freshwater supply. Additional protection may
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Biocidal active ingredients typically used in slimicide formulations
1,4-bis(bromoacetoxy)-2-butene 1-bromo-3-chloro-5,5-dimethylhydantoin (BCDMH) 2,2-dibromo-2-cyanoacetamide (DBNPA) 2-bromo-2-nitroethenylbenzene + MBT 2-bromo-2-nitropropan-1,3-diol (bronopol) 2-bromo-4-hydroxyacetophenone (BHAP) 2-methyl-4-isothiazolin-3-one (kathon component) 3,5-dimethyl-1,3,5-2H-tetrahydrothiadiazine-2-thione (Dazomet) 5-chloro-2-methyl-4-isothiazolin-3-one (kathon component) 5-oxo-3,4-dichloro-1,2-dithiol (Dithiol) alkyl dimethyl benzyl ammonium chloride (ADBAC) potassium-N-hydroxymethyldithiocarbamate sodium bromide sodium dimethyldithiocarbamate (Dibam) sodium hypochlorite tetrakishydroxymethylphosphonium sulfate
ammonium bromide ammonium ethylenebisdithiocarbamate chlorine dioxide chloroacetamide didecyldimethyl ammonium chloride (DIDAC) glutaraldehyde disodium cyanodithioimidocarbonate (DCDIC) disodium methylenebisdithiocarbamate (nabam) hydrogen peroxide K-N-methyldithiocarbamate methylenebisthiocyanate (MBT) N,4-dihydroxy-oxo-benzenethanimidoyl chloride N-[alpha(nitroethyl)-benzoyl)ethylene diamine] peracetic acid poly(oxyethylene)bis(dimethyliminoethylene)dichloride (POIDC)
be affected through the use of various sources of bromine chemistry such as BCDMH and sodium and ammonium bromide or, for example, nonoxidizing biocides such as glutaraldehyde, DBNPA or isothiazolinones (see Table 9.1). Biocides used either singly or in combination that are proven to be effective against a wide spectrum of microorganisms, and which are also shown to break down rapidly to nonhazardous components are likely to be the most appropriate choice in slimicides for use in cooling towers and the papermaking industry [4].
References
References
[1] M.A. Blanco, C. Negro, I. Gaspar, J. Tijero, Slime Problems in the Paper and Board Industry, Applied Microbiology and Biotechnology 1996, 46: 203 – 208. [2] P.N. Cheremisinoff, Handbook of Water and Wastewater Treatment Technology, Marcel Dekker, Inc., New York, 1995, p.833. [3] http://www.alken-murray.com/cooltower.htm. [4] http://www.facilitiesnet.com/NS/NS3 m8cd.html. [5] A. Bruce, J.W. Palfreyman, Forest Products Biotechnology, Taylor and Francis Ltd, London, 1998, p.326. [6] H. Yamamoto, T. Ezaki, M. Ikedo, E. Yabuuchi, Effects of Biocidal Treatments to Inhibit the Growth of Legionellae and Other Micro-Organisms in Cooling Towers,
Microbiology and Immunology 1991, 35, 795 – 802. Ian Gould would like to acknowledge the information taken from Hercules publications ad ben the input from his co-author James Hingston of Safepharm Laboratories Ltd. [7] Standard Test Method for Efficacy of Slimicides for the Paper Industry-Fungal Slime (E 599-89), American Society for Testing and Materials, Philadelphia, 1991. [8] T.M. Williams, D. Shaw, Methods for Evaluating Pulp and Paper Slimicides: A Review, Biodeterioration and Biodegradation 1991, 8, 367 – 368. [9] G.W.A. Milne, Ashgate Handbook of Pesticides and Agricultural Chemicals, Ashgate Publishing Ltd., Aldershot, UK, 2000, p.206.
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General Purpose Preservatives Richard Elsmore
10.1
Introduction
This chapter covers a wide range of biocide and preservative uses. As such, it comprises a heterogeneous mix of applications in which antimicrobial compounds are used. The Biocidal Products Directive (98/8/EC) or BPD [1] makes reference to 23 product types divided into four main groups. Some of these product types cover many different product applications e.g. in-can preservatives. This chapter takes an overview of some of these applications that relate to antimicrobial activity and also includes some applications that are specifically outside the scope of the BPD e.g. cosmetics, pharmaceuticals, and food preservation. Information is included on the consequences of microbial growth, types of microorganisms found and examples of antimicrobials used. Where appropriate reference is made to testing requirements. The following applications are included in this chapter: * * * * * * * * * * * *
Cooling water biocides Cosmetic and pharmaceutical preservation Constructional material preservation Detergent preservation Food preservation Fuel preservation Leather preservation Metalworking fluid preservation Oil and gas exploration and recovery Plastic preservation Polymer emulsion and adhesive preservation Surface coatings preservation
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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Swimming pool and spa treatments Textile preservation Miscellaneous preservative uses
Further details are available in specialist publications covering individual applications. References are made where appropriate to more in depth reviews. Additional information on efficacy testing methods for many of the biocide and preservative applications covered available in the form of a recent survey undertaken by the OECD [2].
10.2
Biocide Selection
The choice of biocide or preservative made in each application area will generally be based on the following considerations: *
*
*
*
* *
*
*
Risk to humans and the environment. Both exposure and hazard of the chemical need to be considered as well as any reaction products and degradation products that may be formed during and after use. Spectrum of activity against the relevant micro-organisms for the particular application (bacteria, fungi, algae, viruses, spores, or vegetative cells etc.). Speed of action – some applications require a very rapid kill, for others a slower kill or even inhibition of growth will be satisfactory. Compatibility in the application (including effect of pH, temperature, corrosivity of the biocide, compatibility with other chemicals that may be present, effect of soiling, solid, liquid or gaseous biocide etc.). Regulatory status of the active ingredient and formulated product. Length of activity – some applications require a stable biocide to provide long-term protection, for others a short life has advantages. Others e.g. taste, smell, color, solubility (in water or oils), flashpoint, vapor pressure, stability in-can etc. Cost effectiveness (last on this list but not least important).
10.3 Biocide/Preservative Application Areas
10.3
Biocide/Preservative Application Areas 10.3.1
Cooling Water Biocides
In cooling water treatment applications, biocides are used primarily to minimize biofouling. This enables efficient operation of the water system, as biological growth and slime formation can lead to reduction of heat transfer, microbially induced corrosion, increased pumping costs and the degradation of other water treatment chemicals such as descalants and corrosion inhibitors. In severely fouled systems, biological growth can even lead to structural damage to the cooling tower and associated pipework. Water treatment biocides are also used to control potentially pathogenic organisms such as Legionella pneumophila (Elsmore, 1999)[3]. There are three main types of cooling system in common use. In “once-through” systems natural water (e.g. sea or river water) is used to cool a process. For environmental reasons this first type is the most sensitive application in respect of biocide choice. The second type of cooling system is the re-circulating water system where cooling water is reused. This type of system is the most common type as it conserves water. Biocides are routinely added to re-circulating cooling systems. The third type is the closed system where the cooling water is not exposed to the atmosphere. In this type of system a secondary cooling system is required e.g. air-cooling. The market for cooling water treatment biocides is supplied by specialist water treatment companies. These companies provide the high degree of services that this application requires. The biocides commonly used include: Oxidizing biocides *
* *
Chlorine gas, sodium, or calcium hypochlorite, and chlorine release biocides (e.g. sodium dichloro-s-triazine, trichloro-s-triazine) Chlorine dioxide Bromine from activated sodium bromide or bromine release agents such as Bromochloro dimethylhydantoin (BCDMH)
Nonoxidizing biocides *
*
Quaternary ammonium compounds (QACs) e.g. alkyldimethylbenzylammonium chloride Bromonitropropanediol (BNPD)
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* *
Bromonitrostyrene Dibromonitrilo propionamide Methylenebisthiocyanate Gluteraldehyde Isothiazolinones e.g. blend of chloromethylisothiazolonone and methylisothiazolonone Imidazolines Phenolics
As with many of the other applications there has been a general trend to more environmentally safe biocides in water treatment application. This has tended to favor chemicals that react rapidly and degrade to nontoxic components. Further details on biocides use in process cooling waters can be found in Lutey (1995)[4]. Standard test methods are available for the testing of biocide formulations used in water treatment, although many companies have developed in-house protocols. A provisional standard has been developed by CEN for the determination of bactericidal activity of products against Legionella pneumophila (prEN 13623)[5]. ASTM also has a range of standard test methods applicable to the testing of biocides for efficacy in cooling waters (US EPA Guidelines, ASTM E-645-97)[6, 7].
10.3.2
Cosmetic and Pharmaceutical Preservation
Both cosmetic and medicinal products may be prone to microbial contamination and spoilage (Beveridge, 1999, Hill, 1995) [8, 9]. Microbial contamination and spoilage can result in a range of problems and hazards, from discoloration, odors, visible growth, and degradation of the formulation components to potential for infection (Beveridge 1998). The potential consequences to health from infected products may be from primary pathogens or opportunistic pathogens such as Pseudomonas spp. Bacterial and fungal spores can prove problematic in dry tablets, capsules, and cosmetic powders. Multi-use products such as cosmetics and creams can also become contaminated with skin flora organisms such as Staphylococcus aureus and Staphylococcus epidermidis. Other micro-organisms which may be important contaminants in cosmetic products are yeasts such as Candida spp and dermatophytic fungi. In addition, microbially produced toxins and metabolic by-products can prove irritating to skin and can induce allergic reactions. Microbial susceptibility will depend on a variety of factors including, pH, moisture content, and the ingredients of the formulation. The opportunity for contamination will also vary depending on the product type with multi-use products being more likely to contamination in use, than for a single shot applications.
10.3 Biocide/Preservative Application Areas
The preservatives required for pharmaceutical, cosmetic, and toiletry applications are generally of a higher specification and purity than those used in many other areas. The preservatives used in cosmetic and toiletry applications include BNPD, Parabens, DMDMH, and benzyl alcohol, phenoxyethanol, sorbic acid, formaldehyde, triclosan, imidazolidinyl urea. This market is highly regulated with the choice of preservatives and their maximum inclusion level being defined in the EU by Annex VI of the Cosmetics Directive (Directive 76/768/EEC)[11]. In the USA the Federal Food, Drug and Cosmetic Act (as amended)[12] cover cosmetics, with the FDA Office of Cosmetics and Colors acting as the enforcing agency. Microbial standards are laid down by national trade associations e.g. CTPA (UK)[13] and CTFA (USA)[14] for cosmetics. Pharmaceuticals products are governed by Directive 65/65/EEC (1965) [15], which lays down objectives for common standards and procedures for safe and effective medicines. In the Europe this now comes under the European Medicines Evaluation Agency which is responsible for granting new medicines marketing authorizations. Preservative efficacy testing has become standardized through the European Pharmacopoeia [16], the United States Pharmacopoeia (USP)[17], and the CTPA and CTFA guidelines. 10.3.3
Constructional Material Preservation
Wood and paint preservation are covered elsewhere in this or other chapters (Chapter 8 and 10.3.12) and so are not included here. This section therefore concentrates on materials such as stone, concrete, and brick and concrete additives. Concrete additives are used to control the viscosity and hardening of the concrete. They are generally based on lignosulfonates, which are in themselves susceptible to microbial degradation. They must therefore be treated with preservatives to ensure that they perform as required. Masonry materials once they become conditioned by the environment (rain, pH, sunlight, and drying) may become colonized by both microscopic and macroscopic growth. During the early stages of colonization, autotrophic bacterial populations tend to colonize surfaces. These include sulfur oxidizing bacteria and heterotrophic bacteria. Although the role of these bacteria in degrading constructional materials is not certain, they will facilitate colonization with higher organisms. Algae will colonize surfaces which remain damp and can cause cosmetic concerns as well as acting as a trap for moisture thus exacerbating the problem. Fungal colonization can also occur under damp conditions and may cause some degradation of masonry and act as a bridge to allow contamination of timbers. Fungi can also facilitate in the process
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of lichen attachment and growth. Lichens will develop on most non-metal surfaces. Under certain conditions they can be considered as disfiguring and they can cause some surface deterioration. Mosses and higher plants can also colonize masonry materials and cause erosion and penetration damage. The commonest approach to the control of these masonry problems is the use of biocidal washes. Typically these are be based on sodium hypochlorite, QACs, or phenolic compounds (e.g. dichlorophen, orthophenylphenol). Further details can be found in Bravery (1999)[18]. Testing methods depend on the product being tested but include soil burial, environmentally controlled cabinets, and exposure tests (see methods referred to under wood preservation and surface coatings). 10.3.4
Detergent and Household Product Preservation
Both formulated liquid detergent products and detergent raw materials can be susceptible to bacteria, yeast and mould growth particularly at lower surfactant levels i.e. below 35 % surfactant. Solid detergent products do not tend to suffer similar attack. In liquid products however, microbial growth can cause problems in bulk storage, during formulation and with the finished product. Traditionally the preservative of choice has been formaldehyde although in more recent years alternative preservatives have been used such as BNPD, isothiazolinones, and formaldehyde release agents. Wide ranges of detergent and household products have been developed to deliver some antimicrobial benefit in use. These range from antibacterial cleaners designed for kitchens or bathrooms, antibacterial mousses or gels, toilet cleaners with biocidal activity, washing up liquids (to control bacterial growth when used neat on dishcloths and sponges), and antibacterial textile wash products. These products have come under some criticism in relation to the actual function that they provide in the home but are generally agreed to provide some hygiene benefits if used as recommended. The biocides used vary depending on the formulation and intended use, but include sodium hypochlorite, quaternary ammonium compounds, and hydrogen peroxide in surface cleaners, and active ingredients such as triclosan in washing up liquids. Acids such as HCl and citric acid are used in toilet cleaners and hypochlorite or hydrogen peroxide based bleaches again for toilet care. Textile wash products tend to use tetra acetyl ethylene diamine (TAED) activated bleach systems to provide antimicrobial activity [19]. This activity prevents cross contamination between garments and malodors and slime formation in the machine. As with other areas, environmental considerations are becoming more important in
10.3 Biocide/Preservative Application Areas
the selection of antimicrobial actives and preservatives for these down the drain applications. Efficacy testing tends to be based around the CEN standards for chemical disinfectants and antiseptics. These tests include phase 1 tests (e.g. EN1040-basic bactericidal activity)[20], phase 2 step 1 tests (e.g. EN1276- quantitative suspension test for the evaluation of bactericidal activity, EN 1650- quantitative suspension test for the evaluation of fungicidal activity) [21, 22], and phase 2 step 2 tests (e.g. prEN13697-quantitative surface test for the evaluation of bactericidal and fungicidal activity)[23]. Phase 3 or field tests under practical conditions tend, to be undertaken by in-house methods as CEN standards have not yet been developed.
10.3.5
Food Preservation
Foods have been preserved since prehistoric times. Traditional methods include dehydration, salting, smoking, and fermentation. However, with the advent commercial processed foods and the availability of more perishable and convenience foods, additional preservation systems have been developed to meet the needs of modern society (Sofos and Busta, 1999, Jay, 1995, Foegeding and Busta, 1991) [24 – 26]. In some instances processing may produce foods that are free from contamination, but more frequently the natural microbial population will be present at a low level. It is the preservatives function to prevent the proliferation of these organisms. Microbial growth on foods will produce chemical and enzymatic changes which can lead to changes in appearance (e.g. color), texture, flavor, smell, consistency, and nutritional value. Foods can also harbor pathogenic micro-organisms, which can present a health risk if present in sufficient numbers. Pathogens including bacteria, viruses, protozoa, and parasites such as Helminths, can all be present in foods. Examples of organisms of concern include Escherichia coli (enteropathogenic strains), Clostridium botulinum, Listeria monocytogenes, Salmonella spp, and Shigella spp. Preservatives combined with good production, processing, distribution, and storage control will provide extended shelf life, allow the food to retain its wholesomeness and ensure safety by inhibiting the growth of pathogenic micro-organisms. The choice of food preservative will be dependent on the food to be preserved. It will be determined by the type of micro-organism to be encountered and the physical and chemical properties of the food. Important considerations are the solubility, pKa, compatibility, and chemical reactivity of the preservative. Preservatives that are used in food preservation as direct additives include: * *
common salt; sugars (e.g. fructose, glucose, sucrose);
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smoke; ethanol; hydrogen peroxide; bacteriocins (e.g. nisin); lactic acid; acetic acid; benzoic acid; propionic acid; sorbic acid; esters of p-hydroxybenzoic acid; sulfur dioxide and sulfites; nitrite and nitrate.
Indirect food additives such as processing aids may also have some antimicrobial activity and aid in preservation; these include antioxidants, EDTA, fatty acids, and sodium bicarbonate. Regulatory control of food preservatives and additives is in place in most countries. For example in the USA, it is regulated by the Food and Drug Administration (FDA) of the Department of Health and Human Services. The list of permitted chemical preservatives and their use conditions are published in the Code of Federal Regulations (CFR), Title 21, parts 170 – 199 [27]. Internationally the Food and Agriculture Organization (FAO) and World Health Organization (WHO) have established ADI doses for food preservatives.
10.3.6
Fuel Preservation
Microbial degradation and spoilage of a wide range of distillate fuels is well documented (Hill, 1995, Hill and Hill 1999) [28, 29]. These problems have been reported in many fuels including aircraft, road, rail, ship, heating, and power generating fuels. In many of these applications biocides are used in combination with good housekeeping measures to minimize microbial growth or to clean up contaminated systems. Microbial growth tends to occur at the oil/water interface, which results from water ingress into the fuel storage system e.g. from condensation. Microbial growth and contamination can give rise to a range of operational problems including microbially induced corrosion, H2S generation, water entrapment and emulsification of the fuel due to the production of microbial surfactants, filter blockage due to biomass and the degradation of other fuel additives. Biocides that are used in fuel systems include boron containing compounds in aircraft fuels and BNPD, isothiazolinones, and oxazolidines in marine fuels.
10.3 Biocide/Preservative Application Areas
Hydraulic oils and other oils such as turbine oils and marine lubricating oils can also suffer from microbial contamination and spoilage. Here remedial action has included the addition of biocidal treatments including TCMTB or, isothiazolinones. Many in-house methods are used for the testing of biocides for efficacy in fuel systems. There is an ASTM method for testing antimicrobials in fuels (ASTM E-1259-94) [30]. It looks at the effect of oil water partitioning and time on antimicrobial activity, as well as the effect of continual challenge.
10.3.7
Leather Preservation
Leather and leather products being natural materials are prone to microbial contamination and spoilage. (McCarthey, 1999, Lindner and Neuber 1990) [31,32]. Microbial problems affects leather manufacture at all stages of production from the wet blue stage through transport, pickling, and tanning to the finalized product. Biocides are used during the curing and pickling of the raw hides and then during tanning and finishing. Due to environmental concerns, there has been a move away from some of the traditional antimicrobials used (e.g. pentachlorophenol). The proteins and fats in the raw hide represent an ideal source of nutrients for both bacteria and fungi. Salt curing at the slaughterhouse has been traditional but unsalted or green hides can be transported to the tannery by the use of chilling or by chemical treatment with preservatives such as QACs, biguanides, chlorinated phenols, boric acid etc. At the tannery the skins are soaked to remove dirt, salt, and soluble proteins. This soaking process can support large numbers of bacteria if chemical preservatives are not used. Typically preservatives used in the soaking process include dithiocarbamates, sodium fluoride, thiocyanates QACs, biguanides, or chlorinated phenols. During the dehairing and liming process conditions are generally unfavorable to microbial growth but the pickling process for chrome tanning will be prone to fungal growth. Stored pickled pelts, wet blues and vegetable tanned moist leather are all prone to mould (and occasionally yeast) growth which may result in damage to the leather. Typical organisms include Trichoderma viride, Aspergillus spp., Mucor spp., Rhizopus nigricans, and Penicillium spp. Preservatives used in the preservation of these processed pelts include thiocyanates (TCMTB, MBT) isothiazolinones (e.g. 2-octylisothiazolinone), QACs, and phenolic based biocides. Preservation efficacy tests are available e.g. ASTM D4576-91 [31] for mould resistance of blue stock (leather).
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10.3.8
Metalworking Fluid Preservation
Metalworking fluids are used to cool, lubricate, and remove fines and swarf from machined tools, dies, and workpieces. These fluids may be non-aqueous if lubrication is the main function but tend to be water-based oil-emulsions (e.g. cutting oils), microemulsions, or chemical based solutions (synthetic fluids) if cooling is the principal function. Typically they will contain a cocktail of chemicals which may include emulsifying agents, corrosion inhibitors, extreme pressure additives, and viscosity controllers. In metal working fluids, microbial contamination can produce fluid degradation, emulsion instability, corrosion, malodor, H2S generation, and may even be linked with health problems from potential pathogens and microbial toxins (Hill and Hill, 1999, Rossmoore, 1995) [29, 34]. Biocides used in these applications include products based on isothiazolinones, dichlorophen, PCMC, OPP, triazines, BNPD, and formaldehyde release biocides. These will be included in the concentrate as supplied to give in-can protection and to provide some activity when diluted. Remedial biocidal treatments and cleaners are also available to extend the life of fluids and to clean systems between fills. Efficacy testing is often undertaken by in-house methods although a range of standards are available. These include ASTM E686-91 [35] and ASTM E979-91 [36] and ASTM E3946-92 [37].
10.3.9
Oil and Gas Exploration and Recovery
Microbial contamination and growth can cause a range of problems at various stages in the drilling, preparation, and production stages of both oil and gas exploration and production. Microbial growth can occur in the fluids used in the drilling process including drilling mud components such as fluid-loss chemicals, viscosifiers, lubricating agents, and fractionating fluids used to increase the surface area of oil the bearing strata. Injection waters used in secondary oil and gas production may contain a variety of chemical additives. These additives can provide a good nutrient source for micro-organisms. If microbiological proliferation occurs, problems of microbial contamination of the oil-bearing strata may result in sulfide souring due to H2S generation by sulfate reducing bacteria. In addition, microbial induced corrosion and degradation of injection water additives can prove extremely expensive. (Hill et al. 1986, Herbert, 1995) [38, 39]. The biocides used in secondary oil recovery are primarily glutaraldehyde based but also include chlorine, biguanides, isothiazolinones, QACs, and BNPD. Due to the
10.3 Biocide/Preservative Application Areas
potential for environmental contamination, there has been a move towards the selection of more environmentally acceptable biocides. Both the American Petroleum Institute (API) and the National Association of Corrosion Engineers (NACE) have methodology for biocide testing. ASTM also has a standard test method for assessing the effectiveness of antimicrobial agents against biofilms which is also appropriate to this application (ASTM E1427-91) [40]. Additionally many companies operate their own in-house methods.
10.3.10
Plastic Preservation
Most modern plastic polymers tend to be resistant to microbial attack (Seal, 1988) [41]. There are exceptions, however, such as low molecular weight polyethylenes and some polyesters and polyester polyurethanes. Plastics will also contain a range of other components including plasticisers, flame retardants, fillers, UV stabilizers, pigments, and lubricants which provide a nutrient source and may promote degradation of the plastic by bacteria and fungi. This can result in loss of structural properties e.g., tensile strength, flexibility, enbrittlement, and cracking. Additionally, surface growth and staining can be unsightly. Microbial growth can also result in the production of malodors. Plasticisers in particular are known to be susceptible to microbial attack and degradation. To overcome these problems biocides are routinely included in plastic products particularly those intended for use or exposure to humid conditions. Products include 10,10-oxybisphenyloxyarsine, isothiazolinones and tin based biocides. Test methods used include soil burial and tensile strength testing depending on the material being tested. In-house tests are frequently used. AFNOR, BS and ASTM test methods are available (see [2] for summary).
10.3.11
Polymer Emulsion and Adhesive Preservation
Polymer emulsions are used in the manufacture of a range of products including paints, paper and textile coatings, and adhesives. They are dispersions or suspensions of synthetic polymers in an aqueous medium. As such, they are prone to microbial attack and degradation. This can be in the form of enzymatic degradation of the formulation and loss of viscosity, gas formation, acidity increase, pigmentation, and blackening (Gillatt, 1990) [42]. Adhesives, sealant, glues, and thickeners are also susceptible to microbial attack and degradation depending on their composition. These products include silicone sealants, acrylic sealants, acrylic adhesives, polyurethane adhesives, vegetable glues (cel-
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lulose, starch), and animal glues. When in aqueous form (rather than as solid powders) they are generally in need of preservation. After application, particularly under humid conditions, glues and adhesives can become contaminated with fungi, which can be both unsightly and result in failure of the bonding. The choice of preservative will be dependent on the type or formulation and, in the case of powders, they will need to be able to withstand the drying process used in manufacture. Protein based animal derived glues and adhesives are particularly sensitive to microbial growth and degradation and are not generally compatible with some preservatives such as formaldehyde and formaldehyde release biocides due to coagulation. Low volatility fungicides are frequently used to control fungal growth in use. In-can preservatives include a wide range of biocidal agents. For applications where there is a potential for food contact, low-toxicity biocides which are odorless and tasteless need to be used. Approval by the relevant regulatory authority is also required for food contact applications e.g. FDA in the USA and the Federal Institute for Consumer Health Protection and Veterinary Medicine (the BgVV) in Germany. The products used are diverse and include sodium orthophenylphenol (SOPP), isothiazolinones such as BIT, dichlorophen, BNPD, formaldehyde, and formaldehyde release agents. Test methods used include soil burial and simulated use testing depending on the material being tested. An in-can test has been developed for adhesives by ASTM (ASTM D4783-97)[43]. In-house tests are frequently used.
10.3.12
Surface Coating Preservation
Emulsion paints can suffer microbial attack which affects the product both “in-can” and in the dry film. Water based emulsion paints typically contain a complex mixture of ingredients including inorganic pigments plus organic components such as polymer emulsions (see 10.3.11), emulsion stabilizers, thickeners, surfactants, dispersants, defoamers, extenders, anti-freeze, and coalescing agents. Many of these components are in themselves prone to microbial attack and degradation. This attack can result in discoloration, product degradation such as loss of viscosity, malodors, frothing and gassing (in cans), ropiness, and phase separation. Biocides are used to preserve the raw materials used in the paints, and also the formulated paint itself to give in-can protection. The products used for preservation include organometal biocides, isothiazolinones, QACs, sulfones, thiazoles, and phenolics.
10.3 Biocide/Preservative Application Areas
Biocides may also be used to give a biocidal property to the paint film itself. Provided suitable leaching and mobility characteristics can be developed, continuous protection of the paint surface can be achieved. Traditional organometal biocides are being replaced by less toxic organic alternatives such as specific isothiazolinones. Some of these compounds are active against not only bacteria and fungi but can also provide protection against algal growth. Antifouling paints are covered separately in more detail in Chapter 13. Test methods used include minimum inhibitory concentration testing, challenge testing (e.g. ASTM D25714-97) [44], soil burial, environmental chambers (ASTM D3273-94, and BS 3900 part G6) [45, 46], and exposure testing (ASTM D3456-91) [47]. In-house tests are also frequently used. More information on paint preservation can be found in Downey (1995) [48] and Springle (1999) [49].
10.3.13
Swimming Pool and Spa Treatments
Swimming pools and spas are essentially re-circulating water systems. The water is usually heated and filtered before being returned to the pool or spa. Nutrients can enter the pool in the form of sweat, urine, skin cells, and occasionally from blood, faeces, and vomit. Other organic matter such as leaves can provide a source of nutrients in the case of outdoor pools. Micro-organisms can enter the pool with the make up water, from environmental contamination and from the bathers themselves. Microbial growth will cause problems such as discoloration of the water, cloudiness, malodors slimes, filter blockage, and even infection. (Singer 1990, Dadswell, 1999) [50, 51]. Algal and fungal growths can occur causing unsightly staining on the walls of the pool, the pool may become hazy or cloudy making it impossible to see the bottom of the pool, and this can cause concern with potential drownings. A range of microbial pathogens have been isolated from swimming pools and have been associated with infections these include: Acathamoebae, adenoviruses, Cryptosporidium parvum, dermatophyte fungi, Giardia lamblia, hepatitus A virus, Mycobacterium marinum, Naegleria fowleri, papilloma virus, Pseudomonas aeruginosa, and Shigella. Pools and spas are similar in the problems they have. The exception being that spas are generally operated at higher temperatures with more agitation and higher relative bather loads. This provides a rich soup of nutrients and will support a higher microbial population, and will also affect the choice of biocide made. The main chemicals biocides used include chlorine gas, sodium and calcium hypochlorite, ozone, chloroisocyanurates. Specialist biocides such as Bromochlorodi-
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methylhydantoin, polymeric biguanides, activated sodium bromide, QACs, and hydrogen peroxide are also used mainly in private pool applications. Efficacy testing tends to be based on in house test methods, which can include pilot (model) and full-scale tests. These may include the use of artificial sweat or the use of volunteers in full-scale trials.
10.3.14
Textile Preservation
Most natural and man made fibers can be susceptibly to microbial attack. This may become evident as staining, bad odors, and loss of structural integrity. Biocides are added as rot proofing treatments, to provide temporary protection during processing or as a hygienic finish. Biocides may also be added to protect workers from pathogenic organisms that may be present on natural fibers (e.g. formaldehyde is used to treat camel hair and cashmere due to concerns over anthrax contamination). The factors that affect susceptibility to microbial attack and biodeterioration include the type of substrate, presence of auxiliary chemicals, dyeing, pH, water activity, temperature, chemical or mechanical damage, and exposure. Organisms of concern include bacteria (Bacillus subtilis, Pseudomonas aeruginosa, Pseudomonas fluorescens, and Bacillus anthracis), fungi (Aspergillus niger, Penicillium spp) and insects (Tineola bisselliella, Tinea pellionella, and Anthrenus flavipes). Compounds used include phenolic biocides such as OPP, dichlorophen as well as organometal products such as copper or zinc napthanate, QAC compounds are also used. Biocide treatment can take place at the spin-finish stage or at the final textile finishing process. Additional information on textile preservation can be found in McCarthey (1999) [31] and McCarthey (1995) [52]. A wide range of national and international standard test methods are available for the testing of textile products. These include pure culture tests, mixed culture tests, perfusion techniques, and soil burial tests (with and without soil infection). Examples of these tests include: British Standard 6085:1992 [53], American Association of Textile Chemists and Colorists (AATCC) Method 147-1993 [54], AATCC Method 30-1993 [55], and AATCC Method 100-1993 [56].
10.3.15
Miscellaneous Uses
Due to the fact that micro-organisms are ubiquitous and very adept at utilizing a range of metabolic substrates, most materials can suffer microbial contamination and spoilage of some sort. Consequently the range of applications where biocides may need to
10.4 Conclusion
be used is very diverse. Many of these smaller application areas are not specifically covered in this chapter. These include such areas as human tissue preservation, milk sample preservation, the preservation of historic artifacts, photographic film preservation etc. Antimicrobial chemicals are also used as agrochemical pesticide and have medical uses (e.g. antiseptics and antibiotics) and have also not been included. Biocidal products are used for the control of higher animals such as avicides, molluscicides, piscicides, and insecticides but have again not been included in the scope of this chapter where the focus has been on microbiological control.
10.4
Conclusion
The applications covered in this chapter give an indication of some of the areas where microbiocidal products serve a vital function in preventing microbiological growth and the associated problems that go with it. These benefits relate to health, environmental, and economic matters. By reducing the risk of infection preservatives and biocides have a significant positive health impact, by preserving and extending the life of products they help to conserve natural resources and the financial benefits achieved by product preservation and for example from optimization of heat transfer by reducing biofouling are significant. The benefits to society of these antimicrobial products are therefore profound. The influence of increasing legislation, consumer concerns, and environmental pressure is resulting in an industry that is changing rapidly. This change has been manifest in the move away from some of the traditional products such as some organometallic compounds, phenolic derivatives, and halogenated compounds to more environmentally acceptable alternatives. Environmental concerns have included possible hormone mimicry, persistence, bioaccumulation, and potential reaction products. Increasing regulatory costs are raising barriers to entry, meaning new biocidal active ingredients are now less likely to be developed. This combined with the fact that fewer active ingredients will be available due to the likely impact of regulatory and cost hurdles such as the BPD will mean that choice of active ingredients will be significantly reduced. The consequence of this for many of the applications covered in this chapter will be that future development will lie in the area of product formulation, using approved active ingredients rather than looking for new compounds. Where active ingredients have been used in niche markets historically, the cost burdens imposed by registration/approval schemes are likely to mean that some current active will no longer be available for use. Environmental concerns will continue to be a significant factors in the choice of biocides in most if not all applications areas, leading to the development and selection of environmentally safer products.
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Proof of product efficacy is becoming more important both through product registration schemes and public pressure; this is resulting in continued standardization of testing requirements which are becoming more relevant to the end use application. The need for antimicrobial products per se in some applications (e.g. some household cleaning applications) has been questioned, and proof of the benefits, if real (e.g. health, hygiene, environmental, and economic) need to be justified and made clear to both the regulator and general public. To conclude, the biocides market is going through a period of rapid change which is leading to an industry that is well regulated and which is producing products that will meet the future needs of mankind both in terms of efficacy and safety.
References [1] Directive 99/8/EC of the European Parliament and of the Council of 16th February 1998, Office for Official Publications of the European Communities, Luxembourg, Off. J. Eur. Communities, L123 24/4/1998, 1 – 63. [2] OECD (2000), Overview of Efficacy Testing Methods for Biocides, OECD, available online at http://www.oecd.org/ehs/ biocides/efficacy-overview.htm. [3] R. Elsmore, Legionella, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.333 – 343. [4] R.W. Lutey, Process Cooling Water, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.50 – 82. [5] prEN13623 CEN, Bactericidal Activity of Products against Legionella pneumophila, Test Method and Requirements (phase2/ step 1), CEN, Brussels. [6] EPA (1999), Product Performance Test Guidelines, OPPTS 810.2700. US EPA. [7] ASTM E645-97 (1997), Standard Test Method for Efficacy of Microbiocides Used in Cooling Systems, ASTM, Philadelphia. [8] E.G. Beveridge, Preservation of Medicines and Cosmetics, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.457 – 484. [9] E.C. Hill, Fuel Biocides, in Handbook of Biocide and Preservative use, ed Rossmoore,
References
[10]
[11]
[12]
[13]
[14]
[15]
Blackie Academic & Professional, Glasgow, 1995, pp.207 – 237. E.G. Beveridge, Microbial Spoilage and Preservation of Pharmaceutical Products, in Pharmaceutical Microbiology, 6th edition, eds W.B. Hugo, A.D. Russell, Blackwell Scientific Publications, London, 1998, pp.335 – 373. Council Directive 76/768/EEC of 27th July 1976 on the approximation of the Laws of the Member States Relating to Cosmetic Products, Office for Official Publications of the European Communities, Luxembourg, Off. J. Eur. Communities, L262, 29/ 9/1976, 169 as amended. Federal Food, Drug, and Cosmetic Act (1997), Chapter VI Cosmetics, US Department of Health and Human Services, FDA, Washington DC. CTPA (1976), Recommended Microbiological Limits and Guidelines to microbiological Quality Control, The Cosmetic, Toiletry and Perfumery Association, London, Revised 1983, 1986, and 1990. CTFA (1976), Microbiological Limit Guidelines for Cosmetics and Toiletries, in CTFA Technical Guidelines, The Cosmetics Toiletries and Fragrance Association, Washington DC: Revised 1985. 65/65/EEC (1965) as amended, Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by Law, Regulation or Administrative Action relating to proprietary medicinal products, Off. J. Eur. Communities, 022, 09/ 02/1965, pp.369 – 373.
References [16] European Pharmacopoeia, Efficacy of Antimicrobial Preservation, Council of Europe, Strasburg. 1996, pp.286 – 287. [17] United States Pharmacopoeia, Microbiological Tests [51] Antimicrobial Preservatives-Effectiveness, in USP1995, 23rd edition, Rockville, 1995, p.1681. [18] A.F. Bravery, Preservation in the Construction Industry, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.583 – 604. [19] V.B. Croud, I.M. George, The Biocidal Efficacy of TAED in Fabric Washing Formulas, Happi, Jan. 1997. [20] EN 1040, Chemical Disinfectants and Antiseptics-Basic Bactericidal Test Method and Requirements (phase 1), CEN, Brussels, 1997. [21] EN 1276, Chemical Disinfectants and Antiseptics – Quantitative Suspension Test for the Evaluation of Bactericidal Activity of Chemical Disinfectants and Antiseptics Used in the Food, Industrial, Domestic, and Institutional Areas, Test Method and Requirements (phase 2/step 1), CEN, Brussels, 1997. [22] EN 1650, Chemical Disinfectants and Antiseptics – Quantitative Suspension Test for the Evaluation of Fungicidal Activity of Chemical Disinfectants and Antiseptics Used in the Food, Industrial, Domestic and Institutional Areas, Test Method and Requirements (phase 2/step 1); CEN, Brussels; 1998: [23] prEN 13697, Chemical Disinfectants and Antiseptics – Quantitative Surface Test for the Evaluation of Bactericidal and Fungicidal Activity of Chemical Disinfectants and Antiseptics Used in the Food, Industrial, Domestic and Institutional Areas, Test Method without Mechanical Action and Requirements (phase 2/step 2), CEN, Brussels, 1999. [24] J.N. Sofos, F.F. Busta, Chemical Food Preservatives, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.485 – 541.
[25] J.M. Jay, Antimicrobial Food Preservatives, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.334 – 348. [26] P.M. Foegeding, F.F. Busta, Chemical Food Preservatives, in Disinfection, Sterilization, and Preservation, (Fourth Edition), ed S.S. Block, Lea & Febiger, Philadelphia, 1991, pp.802 – 832. [27] CFR (Code of Federal Regulations), Foods and Drugs, 21 CFR Parts 170 – 199, Washington DC, United States National Archives of Records Administration, 1996. [28] E.C. Hill, Fuel Biocides, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.207 – 237. [29] E.C. Hill, G.C. Hill, Preservation and Disinfection of Petroleum Products, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.542 – 564. [30] ASTM E1259-94 (1994), Standard Test Method for Evaluation of Antimicrobials in Distillate Fuels (Based on Preliminary Screening and Compatibility), Philadelphia, ASTM. [31] B.J. McCarthey, Textile and Leather Preservation, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.565 – 576. [32] W. Lindner, H.U. Neuber, Preservation in the Tannery, International Biodeterioration 1990, 26 (2-4), Special issue Biocides, ed R. Elsmore, 195 – 203. [33] ASTM D4576-91, Test Method for Mould Growth Resistance of Blue Stock (Leather), Philadelphia, ASTM. [34] H.W. Rossmoore, Biocides for Metalworking Lubricants and Hydraulic Fluids, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.133 – 184. [35] ASTM E686-91 (1991)„ Standard Method for Evaluation of Antimicrobial Agents in Aqueous Metal Working Fluids, Philadelphia, ASTM.
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10 General Purpose Preservatives [36] ASTM E979-91 (1991), Standard Method for Evaluation of Antimicrobial Agents as Preservatives for Invert Emulsions and Other Water Containing Hydraulic Fluids, Philadelphia, ASTM. [37] ASTM D3946-92 (1997), Test Method for Evaluating the Bacterial Resistance of Water-Dilutable Metalworking Fluids; Philadelphia, ASTM. [38] E.C. Hill, J.L. Shennan, R.J. Watkinson, Microbial Problems in the Offshore Oil Industry, John Wiley and Sons, 1986. [39] B.N. Herbert, Biocides in Oilfield Operations, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.185 – 206. [40] ASTM E1427-91 (1991), Standard Guide for Selecting Test Methods to Determine the Effectiveness of Antimicrobial Agents and Other Chemicals for the Prevention, Inactivation and Removal of Biofilm, Philadelphia, ASTM. [41] K.J. Seal, The Biodeterioration and Biodegradation of Naturally Occurring and Synthetic Plastic Polymers, Biodeterioration Abstracts 1988, 2 (4), 295 – 317. [42] J. Gillatt, The Biodeterioration of Polymer Emulsions and Its Prevention with Biocides, International Biodeterioration 1990, 26 (2-4), Special issue Biocides, ed R. Elsmore, 205 – 216. [43] ASTM D4783-97 (1997), Test Methods for Resistance of Adhesive Preparations in Containers to Attack by Bacteria, Yeast and Fungi; Philadelphia, ASTM. [44] ASTM D25714-97 (1997), Standard Method for Resistance of Emulsion Paints in Containers to Attack by Microorganisms, Philadelphia, ASTM. [45] ASTM D3273-94 (1994), Standard Test Method for Resistance to Growth of Mould on the Surface of Interior Coatings in an Environmental Chamber, Philadelphia, ASTM. [46] BS 3900 Part G6 (1989), Method of Testing for Paints. Assessment of Resistance to Fungal Growth; British Standards Institution, London.
[47] ASTM D3456-91 (1991), Standard Practice for Determining by Exterior Exposure Tests the Susceptibility of Paint Films to Microbiological Attack; Philadelphia, ASTM. [48] A. Downey, The Use of Biocides in Paint Preservation, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.254 – 282. [49] W.R. Springle, Paint and Paint Films, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.577 – 582. [50] M. Singer, The Role of Antimicrobial Agents in Swimming Pools, International Biodeterioration 1990, 26 (2-4), Special issue Biocides, ed. R. Elsmore, 159 – 168. [51] J.V. Dadswell, Recreational and Hydrotherapy Pools, in Principles and Practice of Disinfection, Preservation and Sterilization (Third Edition), eds A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Blackwell Science, London, 1999, pp.446 – 456. [52] B.J. McCarthey, Biocides for Use in the Textile Industry, in Handbook of Biocide and Preservative Use, ed Rossmoore, Blackie Academic & Professional, Glasgow, 1995, pp.238-253. [53] BS 6085 (1992), The Method for Determination of the Resistance of Textiles to Microbiological Deterioration, British Standards Institution, London. [54] AATCC 147-93 (1993), Activity of Fabrics: Parallel Streak Method, AATCC Technical Manual. American Association of Textile Chemists and Colorists, North Carolina. [55] AATCC 30-93 (1993), Antifungal Activity, Assessment on Textile Materials: Mildew and Rot Resistance. AATCC Technical Manual, American Association of Textile Chemists and Colorists, North Carolina. [56] AATCC 100-93 (1993), Assessment of Antibacterial Finishes on Fabrics, AATCC Technical Manual, American Association of Textile Chemists and Colorists, North Carolina.
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Disinfectants and Public Health Biocides Kerys Mullen
11.1
Introduction
The control of microbial growth is necessary in many situations such as infections on the skin (antiseptics) and in the body (antibiotics), and preventing the degradation of materials (preservatives). Disinfectants and public health biocides are used to control potentially pathogenic populations in the environment.
11.1.1
Microorganisms – An Overview
Microorganisms are everywhere. They are adaptable and resourceful. General facts about microorganisms * * * *
*
* *
Normally refers to bacteria, fungi, and viruses. Bacteria and fungi require some basic things to survive: food and water. Viruses require a host cell. The availability of food and water determines whether cells are surviving or growing and growth occurs by replication of the cell. Rate of growth is affected by the environmental conditions and cells can very quickly adapt to their surroundings. Temperature and oxygen level can also have an affect on survival. 10 million organisms can occupy the space on a pinhead and so can easily accumulate on small pieces of organic material such as food or in microscopic crevices on a surface.
Bacteria are usually classified as Gram positive or Gram negative, the main difference being in the structure of the cell wall. Under adverse conditions e.g. when water is The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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scarce, a few bacterial species (such as bacillus and clostridium) can form spores. During formation of the spore the cell produces a tough outer protective coat, which make it exceptionally resistant to heat, drying out and biocides. Spores can remain viable in a dormant state for many years, and a new bacterial cell will grow out from the spore when growth conditions improve. Fungi range from small single cells such as yeasts to large complex structures such as mushrooms. The high humidity and temperatures often found in bathrooms and kitchens are conducive to fungal growth. Fungi can also be responsible for infections and they can cause an allergic response similar to hayfever or asthma. Fungi can also cause discoloration and deterioration of surfaces giving the characteristic blackening as well as unpleasant odors. Viruses are very small and are not a true cell so they must be inside a living cell to replicate. They have genetic material but lack cell components to enable growth. Viruses can infect bacteria, fungi, plants, animals and humans and can remain viable on surfaces for a long time, even in dry conditions.
11.1.2
Harmful and Nonharmful Organisms
Not all bacteria cause disease. Most cannot cause disease. Many even play beneficial roles e.g. producing antibiotics, and our bodies are covered with commensal bacteria (the normal flora). Some free-living bacteria and members of the normal flora are potentially pathogenic. This means that when an individual is immuno-compromised, potentially pathogenic organisms can cause disease. Even among bacteria that can cause disease, only a few species are always pathogenic (Tables 11.1 and 11.2). Tab. 11.1.
Some pathogens associated with a particular disease
Pathogenic organism
Disease
Mycobacterium tuberculosis
Tuberculosis
Vibrio cholerae
Cholera
Shigella spp
Dysentery
Legionella pneumophila
Legionnaire’s disease
Tab. 11.2.
Some illnesses caused by different species
Pathogenic organisms
Disease
Campylobacter spp., Salmonella spp
Diarrhea
Streptococcus pneumoniae, Haemophilus influenzae
Pneumonia
Neisseria meningitidis, Streptococcus pneumoniae
Meningitis
11.2 Disinfection and Disinfectants
11.2
Disinfection and Disinfectants
The number of microorganisms in a particular situation can be controlled in any or all of the following ways: mechanical removal, thermal disinfection and, chemical disinfection. Disinfectants and biocides provide chemical disinfection. Disinfection is a process of reducing microorganisms to a level that is not harmful to health. There are two types of chemical agents used to control the growth of micro-organisms; agents which kill cells known as biocidal agents and agents which inhibit growth of cells (without killing them) known as biostatic agents. So bactericidal refers to killing bacteria and bacteriostatic refers to inhibiting the growth of bacterial cells. In the same way a fungicide kills fungi and so on.
11.2.1
Disinfection Procedure
There are some situations where the use of a disinfectant is a legal requirement for example sanitizing milking equipment; during the outbreak of a notifiable disease in animals; in abattoirs and slaughterhouses; on licensed drinking premises in Scotland; and for teat dips and sprays used in milking. There are also guidelines for public swimming baths.[1] There are many other situations where a disinfectant is routinely used such as: * * * * *
When individuals are particularly susceptible to disease (immuno-suppressed) During a surgical procedure In food and beverage industry In animal health procedures When preparing pharmaceutical products [1]
The disinfection process can be a single step where the disinfectant is the sole means of controlling microbial growth such as contact lens solution and disinfection of household surfaces. The disinfection process can also be a multi-step process where chemical disinfection can be used along with mechanical or thermal disinfection such as in industry where disinfection usually follows a cleaning and rinsing step. Different species of organisms can cause infection and disease in different ways. Some microorganisms only require cells to cause disease whereas others require 10 million cells. People can be infected in different ways such as through the air, by people contact, ingestion (food or water), inhalation and insect bite [4]. Whether the infection causes
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disease or illness depends on the condition of an individual’s immune system. For example, a normal healthy adult is more resistant to illness than an elderly person, an infant, or individual with chronic disease (such as cancer). Understanding how the product will be used and the risks of infection are important aspects a formulator must consider when designing a disinfectant.
11.2.2
Designing a Disinfectant
One type of disinfectant may not be appropriate for every situation (see Tables 11.3 and 11.4). For example, hypochlorite is active against most types of organisms as long as Tab. 11.3.
Factors considered when designing a disinfectant
Target organism(s)
The way it is applied
Level of soiling
Toxicity
Solubility
Target surfaces
Contact time
Odor
Temperature
Cost
Tab. 11.4.
Factors affecting the effectiveness and limitations of four common disinfectants
Factor
Sodium hypochlorite
Hydrogen peroxide
Phenolic
Quaternary ammonium
Effective against Vegetative bacteria Gram +
+
+
+
+
Gram –
+
+
+
(+)
Mycobacteria
+
(+)
(+)
–
Bacterial spores
+
–
–
–
Fungi
+
–
(+)
(+)
Viruses
+
(+)
(+)
(+)
Protozoa
+
(+)
–
–
Concentration needed
<0.1 %
5%
1%
>0.5 %
Odor
Slight
No
Strong
No
Taints food
No
No
Yes
No
Inactivated by organic dirt
Yes
Some
No
No
Effect on materials
Bleaches fabrics, corrodes some metals
No
Attacks some plastics
No
Key: + effective; (+) partly effective (some species, at high concentrations);-not effective. [Source: Understanding Germs Hygiene And Health: BACS, 1999].
11.2 Disinfection and Disinfectants
the concentration is right. In situations of high soiling hypochlorite is more likely to fail disinfection because it is inactivated by soil. Also hypochlorite would not be appropriate for disinfecting fabrics because of its bleaching effect [4].
11.2.3
Types of Disinfectant Agents Acids Both inorganic and organic acids can be used for disinfection. Inorganic acids such as nitric, hydrochloric, sulfuric, phosphoric, and sulfamic are used mainly as cleaners for removing limescale but do have some microbiological properties too. There are lim11.2.3.1
itations for their use however because they are corrosive and require strict safety measures when handling them. Examples of organic acids are benzoic, acetic, formic, and citric acid. Possessing some fungicidal and viricidal activity they are usually formulated in combination with other disinfectants [1]. Alkalies Sodium hydroxide is used extensively in the food industry as a general disinfectant and is particularly good at penetrating soil and removing grease. Usually used at high temperatures and concentration to ensure disinfection. Like acids it is corrosive and must be handled carefully [1]. 11.2.3.2
Alcohols Alcohols such as ethanol, isopropyl alcohol at 60-70 % concentration are quite effective disinfectants and are often included in formulations to enhance activity. Being highly flammable though does restrict where it can be used commercially [1]. 11.2.3.3
Aldehydes Formaldehyde and Glutaraldehyde are highly effective disinfectants having wide spectrum of activity including spores. However they are relatively slow in action and they can be both toxic and irritants and so must be handled very carefully [1]. 11.2.3.4
Biguanides An example is chlorhexidine which has a broad spectrum of activity but can be inactivated by organic matter. It is active between pH 5 and 7 but is inactivated by hard water. Chlorhexidine is most compatible with cationic surfactants. It is relatively nontoxic, noncorrosive and does not taint and so is usually formulated to be used as an antiseptic or skin sanitizer [1]. 11.2.3.5
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Chlorine Active Compounds Chlorine gas can be used for the disinfection of water. It is extremely effective having a broad spectrum of activity but is inactivated by the presence of organic soil. Sodium hypochlorite solutions are used extensively and generate available chlorine. Hypochlorite solutions do not wet surfaces well and consequently are often formulated with an appropriate surfactant to enhance the surface action. Solutions of >5 % are classified as irritant and >10 % corrosive. Care should be taken when using these products as they can emit toxic gases when mixed with acids and react violently with other chemicals. Although the antimicrobial action is rapid these products can be corrosive to metals and some other surfaces. Their activity declines over time especially in warm conditions. Hypochlorites of sodium, potassium, calcium and lithium exist all having similar properties. Other chlorine active compounds include trichloroisocyanuric acid, sodium dichloroisocyanurate, dichlorodimethyl hydantoin, chloramine T. Their activity is related to their solubility and the amount of available chlorine present. They can be used with detergents or builders to make powders or tablets [1]. 11.2.3.6
Iodophores These products contain iodine complexed with some other chemical such as a detergent and stabilized by the presence of acids. Often used as surgical scrubs though, iodine is usually buffered and formulated with polyvinylpyrrolidine (PVP). Having a wide spectrum of activity and capable of performance under heavy soiling, they are widely used as dips or sprays for animal teats. However they must not be mixed with other chemicals and quickly lose their activity in alkaline conditions. Also staining may occur and they are moderately corrosive on some surfaces. They are quick acting but high temperatures should be avoided as iodine gas may be released [1]. 11.2.3.7
Phenolic Disinfectants There are several types of phenols in common use. 11.2.3.8
Light-duty phenolics Based on chlorinated phenols these are familiar pine or aromatic disinfectants. They tend to be bactericidal only and work best in higher temperatures, with little or no soiling and in soft water. They are practically nontoxic and do not require special precautions in-use. There is a possibility of tainting and so should not be used in food areas or in milking dairies. Heavy-duty phenolics The following examples are all corrosive to plastics, rubber or sealing materials and have a strong smell of tar:
11.2 Disinfection and Disinfectants
Clear soluble phenolics are based on homologues of phenol dissolved in a soap or surfactant, some alcohol may also be present. They get their name from giving a clear solution when diluted in water, however more modern solutions may give a light emulsion. A good example is Lysol BP, which is a solution of cresylic acid in soap. Toxic and corrosive these products should be handled with care. They have a wide range of activity, are quick acting and effective under heavy soiling. Black fluids are amongst the oldest type of formulated disinfectants. They consist of refined tar products dissolved in carrier oil and emulsified with soap or detergents. Effective under heavy soiling and having a spectrum of activity against bacteria and fungi, they can be irritants and harmful. White fluids are colloidal emulsions of refined coal tar products in water. Again, effective under heavy soiling and having a spectrum of activity against bacteria and fungi, they can be irritants and harmful. They are commonly used in brackish or salt water [1].
Peroxygen Disinfectants Products that release hydrogen peroxide may have good microbiological properties. Hydrogen peroxide itself has been used as a disinfectant at concentrations ranging from 1 % to 20 %. It is a very reactive material and in low dilution can be used as a wound cleaner and antiseptic. Peracetic acid is a common example of the peroxygen compounds. This is a mixture of hydrogen peroxide, acetic acid, and peracetic acid. This product has a very broad spectrum of activity, rapid action and tolerance to heavy soiling and combined with a good environmental profile and low mammalian toxicity has lead to its general use. However, its corrosive nature on skin and particularly metals is a disadvantage [1]. 11.2.3.9
Quaternary Ammonium Compounds (QACs) These compounds first came into use just before the Second World War, although they were not used in domestic products until the 1960’s. The main advantage is that they have no odor and do not taint food, and they are colorless and mild enough for antiseptic use. This type of biocide is used in the food, dairy and brewing industries as well as the medical field. They are incompatible with soaps and have far greater activity against Gram positive bacteria than Gram negative. They also tend to have bacteristatic activity rather than bactericidal and so will be formulated with alcohol and chelating agents to enhance performance. They tend to attach to surfaces because of the atomic charge, although there are a number of different QACs which give rise to different microbiocidal and other properties. They are toxic when concentrated but generally nontoxic at concentrations of 5 % or less. [1] 11.2.3.10
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Amphoterics Long chain alkyl amine acid type compounds are extensively used in the food and pharmaceutical industry for their biocidal properties. They are relatively nontoxic, low in irritancy and moderate spectrum of activity. Some amphoterics are both bactericidal and fungicidal. These types of compounds are less restrictive than QACs being easily rinsed, compatible with most types of detergents and less affected by water hardness. However they are affected by soiling and are only recommended for use on pre-cleaned or lightly soiled surfaces [1]. 11.2.3.11
11.3
Detailed Examples of Disinfectants 11.3.1
Hydrogen Peroxide
Hydrogen peroxide (HP) has been recognized as a biocide for over a century. However during this time its uses have been limited by its instability in formulations. HP is a colorless, almost odorless liquid, which decomposes on contact with oxidizable organic matter, certain metals, and in alkaline conditions. It is incompatible with reducing and other strong oxidizing agents. Mode of Action HP acts through production of the very powerful oxidizing agent, the hydroxyl free radical, which can attack proteins, membrane lipids, DNA, RNA, and other essential components. 11.3.1.1
Factors Affecting Performance Heat and HP together can increase microbial kill. UV irradiation and HP work synergistically together and this is thought to be due to the formation of reactive hydroxyl free radicals. Synergy only occurs if they are both used simultaneously rather than successively. Increased kill is more pronounced against spores than vegetative bacteria. A combination of ultrasonic waves with HP can be more lethal than either of these two factors alone. The sporicidal effects of certain metal ions potentiate the action of HP against some bacterial spore types. The most active metal ion is copper while iron has a lesser effect. It is thought that metal ions catalyze the decomposition of peroxide to free radicals. 11.3.1.2
11.3 Detailed Examples of Disinfectants
Applications The sporicidal activity of HP has lead to its use in aseptic packaging techniques. It has been used for sterilization of blow moulded plastic cartons for packaging milk and fruit juices. It has been used for disinfection of surgical implants, thermal-sensitive plastic equipment, eating utensils, clothing, ventilators, ambulances, and teeth. A 3 % HP solution appears to be the most satisfactory agent for disinfecting hydrophilic soft contact lenses. Its medical uses include a 6 % HP solution to cleanse wounds and 1.5 % HP solution as a dental mouthwash. HP decomposes to water and oxygen and is therefore useful where no toxic residues are permitted and its use in water treatment and food processing is possible because it contains no taste or color. HP can be used at low concentrations to sterilize drinking water. In some countries HP is used in conjunction with a polymeric biguanide compound for the disinfection of swimming pools. HP is approved for food use in many countries such as in the USA it is an antimicrobial agent for raw milk in the preparation of cheese. Heat or the enzyme catalase can destroy the excess HP. However, HP may be undesirable in food due to production of oxidized flavors, bleaching of color and destruction of key nutrients such as vitamin C. 11.3.1.3
11.3.2
Quaternary Ammonium Compounds
As the name implies quaternaries are derived from ammonium salts by replacing some or all four hydrogen atoms surrounding the nitrogen with organic groups. The nature of these organic groups changes the properties of the molecule quite significantly. For example, the chain length considerably influences antimicrobial activity. The highest activity is shown when the chain length is between 11 and 17 carbons. The longer chain length (>20) QACs (see Figure 11.1) have little or no antimicrobial activity. Mode of Action The theory that is generally accepted today is that QACs disorganize the cell membrane. With long fatty chains of carbon atoms connected to a positively charged nitrogen atom, they penetrate in between and disrupt the similar phospholipid molecules that make up the cell membrane. This makes the cell leak vital cell chemicals. They may also denature the enzymes essential for growth. These compounds are not as effective against Gram negative bacteria and this is thought to be due to the positive charge on the molecule making it hard for it to penetrate the outer wall of these bacteria. QACs are primarily bacteristatic but continued contact can result in death. The speed of death depends on a number of factors, the main one being concentration. 11.3.2.1
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Fig. 11.1.
Examples of quaternary ammonium compounds [4]
Factors Affecting Performance Generally the antimicrobial activity of QAC’s increases with temperature. In common with most other disinfectants the antibacterial properties of QACs are markedly reduced in the presence of organic matter. It is thought to be that the organic surface is similar to bacteria and so competes for the QAC. QACs have a higher bactericidal activity in alkaline conditions. Acidity decreases the efficiencies of many QACs to such an extent that at pH 3 their activity almost disappears. The increased activity at higher pH indicates that the base is the active form. QACs are completely inactivated by anionic and some nonionic compounds including soaps, sodium lauryl sulfate, and Tween 80. This neutralization is due to the interaction between the 2 different ionic species. QACs are incompatible with phospholipids. With fatty substances the QACs orientate themselves in layers with the hydrophobic end directed towards the inner fat surface and the hydrophilic, germicidal end towards the outside. Ions particularly calcium and magnesium reduce the bactericidal activity of QACs especially against Gram negative bacteria. The bactericidal activity is reduced according to the valency of the metal ion i.e. trivalent ions have a greater effect than divalent ones. The cations compete for the QAC sites on the cell wall. This factor needs to be considered particularly if the disinfectant is to be diluted in tap water. Chelating agents can improve the activity of the QACs by both disrupting the ions contained in the cell wall (making it weaker) and mopping up the ions in hard water. QACs are surface-active agents and therefore readily adsorbed onto any surface including glass, metal, and plastic so the product container can ultimately affect activity of these disinfectants. Also, any precipitated matter can remove QACs from solution and so reduce activity. 11.3.2.2
Applications QACs were initially used as an aid to surgery such as preparing the patients skin, in a surgical scrub and disinfecting surgical instruments. However using on instruments 11.3.2.3
11.3 Detailed Examples of Disinfectants
is not recommended since QACs can cause corrosion and have limited activity against the range of microorganisms. However due to their properties of nontoxicity and nonirritancy they can be applied to delicate membrane areas and consequently have uses in urology, obstetrics and gynecology. These actives can also be used as preservatives for injection and ophthalmic solutions and for environmental disinfection of floors, walls and equipment in hospitals, nursing homes and public places. QACs are used extensively throughout the food and brewing industry for cleaning and disinfecting floors, plant and surfaces. Their benefits to the industry are that they are odorless, nonstaining, practically tasteless and relatively nontoxic. The Dairy industry is one of the biggest users of QACs in UK. However, the QAC formulation has to be approved by the authorities. In industry QACs can be recommended for treating process water in paper mills and in cooling water systems to prevent microbial damage to the heat exchange units.
11.3.3
Sodium Hypochlorite
Originally discovered over 200 years ago, it is still in widespread use in the form of household bleach (see Table 11.5). This is normally a 5 % solution often thickened with surfactants to provide good dirt penetration and prolong contact. For many purposes it is remarkably efficient disinfectant even compared with most modern alternatives. Because of their wide acceptance as disinfectants in many industries, hypochlorites serve as standards for testing of other disinfectants. Mode of Action As hypochlorites (see Figure 11.2) are oxidizing biocides, they work by changing important molecules within the cell either so that they cannot work properly or destroying them completely. Even at low concentrations hypochlorite oxidizes enzymes, DNA and other functional components as well as components of the outer wall which can cause 11.3.3.1
Tab. 11.5.
Advantages and disadvantages of using hypochlorite as a disinfectant
Advantages
Disadvantages
– Proven and powerful germicides controlling a wide spectrum of microorganisms – De-odourizes – Nonpoisonous at use concentrations – Free of residual poisons – Colorless and nonstaining – Easy to handle – Economical
– inactivated by organic matter – chlorine gas is given off when mixed with acid or if pH is below 5 – corrosive to metals wood, some fabrics etc. – bleaches some fabrics at high concentrations – unpleasant smell at high concentrations – there could be a rapid re-infection after treatment with hypochlorite (short time of activity)
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Available chlorine is a measure of the oxidizing capacity. When hypochlorites are added to water they undergo the following reactions:
Fig. 11.2.
Reactions of hypochlorites in solution
lysis. At higher concentrations, it can oxidize proteins that make up physical structure of the cell so that it physically disintegrates. This considerable oxidizing power makes it effective against all kinds of microorganisms, even bacterial spores. Factors Affecting Performance The biocidal effectiveness of hypochlorite depends on various factors. It largely depends on the concentration and pH. An increase in pH decreases the biocidal activity of chlorine and a decrease has the opposite effect. It is logical to suppose that with increasing concentration there is a corresponding increase in antibacterial activity. This supposition holds true as long as other factors such as pH, temperature, and organic content are held constant. Increasing temperature also leads to increased biocidal effectiveness. However, organic matter consumes the activity of hypochlorite (available chlorine) and reduces its capacity for bactericidal action. Examples of organic matter include body fluids, tissues, microbes themselves, vegetable matter, and egg albumin. Generally water hardness components such as Ca2+ and Mg2+ ions do not affect the effectiveness of the hypochlorite solution. However there can be a mild effect to reduce activity and this is thought to be when water hardness influences the pH. Sodium hypochlorite alone has poor wetting power. The addition of detergent improves this and enhances activity because there is better coverage of a surface. The presence of both hypochlorite and methanol or other alcohols enhance sporicidal activity. The addition of alkali has been shown to alter the structure of spores and may weaken them for chlorine attack. 11.3.3.2
Applications Today they are used as sanitizers in most households, hospitals, schools and public buildings. They are also widely used in restaurants, water fountains, food processing 11.3.3.3
plants, dairies, canneries, breweries as well as being used to treat swimming pools,
11.3 Detailed Examples of Disinfectants Tab. 11.6.
Some uses of hypochlorite and the required level of activity
Use
Available chlorine required [ppm]
Toilet/drains/dustbins general
100 000
Babies bottles
125 to 150
Dairy equipment
250 to 300
Food preparation surfaces – no soil
100 to 200
Food preparation surfaces – with soil
1000
Mains water
0.6
Swimming pools
1 to 3
Swimming pools – foot baths
100
Irrigation of wounds
5000
Soiled equipment (hospital)
10 000
Footbaths (athletes foot)
1000 to 12 000
Mouthwash
500 to 1250
drinking water, sewage, and waste water effluents. In the home environment hypochlorite is most commonly associated with toilet hygiene and hypochlorite can also be used to disinfect drains and dustbins. However, now some general household disinfectants contain hypochlorite, and are used to clean the bathroom and kitchen surfaces. Hypochlorites are a good choice in the kitchen where they are well suited to the disinfection of food preparation surfaces. Their odor quickly disappears and does not taint food. Babies bottles and teats can be sterilized by immersing them in a solution of hypochlorite. In dairy industry the cleaning of equipment as specified in the English and Welsh regulations requires that a detergent wash with available chlorine is used, and this is followed by a rinse with a weaker solution. In the water industry, water borne infections have been controlled by the use of hypochlorites since the middle of the last century. For a long time chlorine gas was the most widely used disinfectant for swimming pools. Sodium hypochlorite though is a safer alternative and since 1985 this has been recommended. Chlorine and hypochlorites have been used effectively in the field of sewage and wastewater treatment. Specific uses in the medical environment include disinfection of equipment soiled with blood, in foot baths to prevent the spread of infection and mouthwashes (see Table 11.6).
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11.4
Efficacy of a Disinfectant
An important aspect to designing a disinfectant is in the verification that the performance will be suitable for the end use. Disinfectants must be able to reduce the number of microorganisms so that they are no longer harmful to health. Failure for some of these products can have serious health consequences. For example, failure of a disinfectant treating surgical equipment can have very different consequences than a disinfectant treating a dustbin. For this reason in some areas there are strict rules and standards that need to be achieved. In general the principle of testing the efficacy of a disinfectant follows three phases [5]:
11.4.1
Phase I – Biocidal Activity
Biocidal activity is measured using a standard laboratory test. This is to verify that the biocide is active in the proposed formulation. A suspension test is used which involves addition of standard microorganisms to a test solution for a specified time. The number of viable cells recovered is an indication of the level of performance for a particular disinfectant.
11.4.2
Phase II – In-use Testing *
*
Step 1 Laboratory methods are used to imitate conditions likely to be found in the product end use. Again a suspension test is used but in this case various standard organisms, water hardnes; and soiling levels can be included in the test parameters. Step 2 This is also a laboratory test but the principle is that the end use is simulated as much as possible. The product is held and delivered in its container, environmental organisms may be used, and the product is applied to a relevant surface.
11.4.3
Phase III – Consumer Test
This is an opportunity for the consumer to use the product and to estimate the risks of infection during any given procedure. This usually involves environmental swabbing to enumerate viable organisms in key sites before and after using each product. A benchmark should always be used to estimate whether the risk of infection is better or worse than using the benchmark product. This type of testing depends on high
11.5 Concluding Remarks
repetition and statistical analysis to estimate the risk of contamination rather than obtaining a definitive value for performance.
11.4.4
Issues with Testing
Even standard surface testing can give variable test results and consequently initiates a lot of debate between microbiologists. Variability in results stems from possible organism/surface interaction and/or product/surface interaction. The key to building confidence in testing of this sort is a high level of standardization (such as when preparing micro-organisms and product neutralization) and including performance controls in every test. When testing moves to the consumer-relevant situation, not only does the diversity of environmental conditions such as type of organisms, soils and surface enhance variability but also the way in which the consumer applies the product. Experimental design and statistical analysis are key to the success of this kind of testing. Consumer tests are resource intensive and time consuming and are not commonly used to substantiate product performance.
11.5
Concluding Remarks
In recent years there have been several issues raised about public health and hygiene and using disinfectants. Discussion has included that disinfectants are contributing to increased resistance to antibiotics. Whilst the debate about this and other issues continues, there is a genuine concern expressed by both the general public and healthcare professionals. With confidence in disinfectants so low the industry must take the initiative in restoring credibility in their products which have undoubtedly had a significant effect on public health and interaction with the environment. With disinfectants coming under the control of EU legislation for the first time, this offers members of the industry the opportunity to form a cohesive and coherent voice to challenge the many detractors.
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References
References
[1] British Association for Chemical Specialities: Guide to the Choice of Disinfectant, 1990. [2] S.B. Block, Disinfection, Sterilisation, and Preservation, 5th edition, 2001. [3] A.D. Russell, Destruction of Bacterial Spores, Academic Press, 1982. [4] British Association for Chemical Specialities: Understanding Germs, Hygiene and Health, 1999.
[5] BS EN 1276 (1997), Chemical Disinfectants and Antiseptics–Quantitative Suspension Test for the Evaluation of Bactericidal Activity of Chemical Disinfectants and Antiseptics Used in Food, Industrial, Domestic, and Institutional Areas. Test methods and Requirements (phase 2, step 1). [6] A.D. Russell, W.B. Hugo, G.A.J. Ayliffe, Principles and Practice of Disinfection, Preservation and Sterilization, 1982. [7] The International Scientific Forum for Home Hygiene, www.ifh-homehygiene.org.
12.1 Introduction
12
Rodenticides and Insecticides Alan Buckle
12.1
Introduction
Rodenticides and insecticides are widely used to protect our health, well being, and environment. At home, in our workplaces, while we travel and during our leisure activities, we are protected from pests and diseases by applications of products containing these biocidal compounds (Chapter 1). The scope of the biocidal uses of rodenticides and insecticides is extremely broad. Generally, they are used for the benefit of public health but, for example, their uses may range from the application by a homeowner of a single rodenticide or insecticide bait to control a small mouse or cockroach infestation to the application by a municipality of an insecticide fog, over a wide urban area, to reduce infestation of insects that transmit human diseases. Distinctions between the scope of biocidal uses of rodenticides and insecticides and applications in crop protection and animal husbandry are by no means clear-cut. For example, a single rodenticide application on a farmstead may be made in order to prevent the loss of stored agricultural produce, to protect the same produce from being spoiled by rodent feces and urine, to prevent damage to structures such as electrical wires, to maintain the health of farm animals and to protect farm workers from such diseases as leptospirosis. These uses encompass crop protection, animal husbandry and public health. Similar considerations might be applied to applications of many insecticides. The treatment that rodenticides and insecticides receive in this chapter will be necessarily “broad brush”. No attempt is made to cover the use of insecticides applied directly to grain for its protection against stored product insect pests [1], nor to deal with products used on and within animals for the preventative or curative treatment of veterinary diseases. However, uses of rodenticides and insecticides in structures housing animals and stored produce are considered.
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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12.2
The Market for Rodenticides and Insecticides as Biocides
The market for the biocidal uses of rodenticides and insecticides is addressed in more detail elsewhere in this book (Chapter 2.). The value of this market globally is the source of considerable discussion but is currently estimated, at the level of those companies supplying the products used, to be in the region of US$ 1.1 billion annually. Caution is required in the interpretation of market data from different sources because the values obtained depend on the level at which the market is assessed. For example, the estimated size of the consumer retail market may vary by as much as an order of magnitude depending on whether it is valued at the level of the company that supplies the active ingredients used in the products or at the level of the prices of products to the end-user. The market for the biocidal uses of rodenticides and insecticides is generally considered to fall into three sectors: household (also called home and garden, consumer retail or “over-the-counter”), professional and municipal. The business of supplying these markets is the province a large number of companies, including both major agrochemical and consumer retail companies with global operations, as well as a range of smaller companies, specialized either by geography or by the types of products developed and traded. Many of the rodenticide and insecticide compounds used as biocides are also present in crop protection. Indeed, in the case of insecticides, only very few were specifically invented for use as biocides, the majority being first developed by agrochemical companies for use in agriculture. On the other hand, rodenticides are customarily researched and invented by smaller companies, because the market for them is relatively limited and their development requires specialized expertise and research. Generally, however, business interest is growing in all these markets. This is because the markets themselves are growing, affected by such factors as urbanization, rapid population growth, the spread of human diseases facilitated by global travel, and a lower human tolerance for insect and rodent pests in the home and urban environment. There is also a growing belief that climate change, whether the result of global or local temperature fluctuations, is leading to the movement northwards of a number of problematic insect pests, such as mosquitoes and termites [2].
12.2.1
Consumer Retail Market
The range of insecticide and, to a lesser extent, rodenticide products sold in the consumer retail market is truly enormous. This is borne out by a visit to the shelves of almost any supermarket or hardware store, either in temperate or tropical latitudes.
12.2 The Market for Rodenticides and Insecticides as Biocides
The value of this market, at the level of sales of active ingredients from manufacturers, has been put at about US$ 320 million. The market is characterized by “consumer values”, including the importance of “branding”, a requirement for simplicity and convenience in use, the need for constant innovation and for (even greater than normal) awareness on the part of manufacturers of the need for safety because users are amateurs. Pests important in the consumer retail sector include, cockroaches, ants, flies, fleas, spiders, scorpions, wasps (and other stinging Hymenoptera), clothes moths, silverfish (Thysanura), house dust mites, centipedes and millipedes (Myriapoda) and, of course, rats and mice. Aerosols are the product of choice in most circumstances for insect control. These are in two main categories, flying insect killers (FIKs) and crawling insect killers (CIKs). Knockdown agents (KDAs), as well as killing agents, are used in most aerosol formulations to produce the rapid effect required by homeowners. Other formulations commonly used include combustible coils, electric emanators, vapor emitting mats, smokes, baits, and sticky traps (often containing no biocide but, sometimes insect attractants). For rodent control, physical control methods are equally as important as biocidal baits and these include a wide variety of traps, as well as “sticky boards” – surfaces carrying strong adhesives on which rodents become trapped and die from suffocation. Rodenticide baits are usually based on cereals and may be in the form of whole or cut grains surface-treated with rodenticide, or extruded pellets made from milled cereals which incorporate the rodenticide either as a liquid or a dust. Rodenticide wax blocks are increasingly used because these are capable of being secured within tamper-resistant bait boxes, thus conferring a significant safety advantage. Wax blocks are available in many different shapes and sizes and are made by processes of compression, extrusion and hot casting. 12.2.2
Professional Pest Management (PPM) Market
Many different industries require the services of companies providing a professional service of insect and rodent pest management – pest management professionals (PMPs). These include homeowners, service industries, particularly those involved with the storage, handling, preparation and sale of human and animal foods, as well as farmers and those involved in animal husbandry. Indeed, in many countries it is a condition of the commercial licenses of such businesses that their premises are regularly inspected by a PMP, or by “in house” personnel who are appropriately skilled in PMP practice. The PPM market is traditionally split into three main sectors, those dealing with termites, general pests, and rodents. The value of products supplied by manufacturers to PMPs for the control of these pests is about US$ 550 million annually.
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The services that PMPs provide go far beyond the application of biocides, though this is an important part of their business, and include a wide range of inspection and preventative operations. It is generally the objective of a PMP to keep the premises of his customers virtually free of pests, because their presence could potentially severely damage the business in question. The pest spectrum encountered by PMPs is similar to that listed for the household sector, though the scale of pest problems, in the commercial and agricultural segments at least, is potentially far greater. To the list of species common in household situations may be added certain species of birds, such as starlings, sparrows, and pigeons (though PMPs will only rarely use biocides as the solution to bird pest problems) and a range of wood-destroying insects, such as subterranean and dry-wood termites and wood-boring beetles. The methods used by PMPs for rodent control vary from those used by homeowners mainly in terms of the scale of their application. Baits, bait boxes, traps, and sticky boards predominate, with the occasional use of fumigation. For insect control the range of products used by PMPs is very large. Liquid formulations, applied as residual deposits using compression sprayers, are still very important. This type of application is used for the control of crawling and nuisance insects, both indoors and increasingly outdoors, for soil treatments in the control of subterranean termites, both pre- and post-construction, and for surface treatment of wood for the control of wood-destroying insects. A very wide range of insecticide baiting strategies has become increasingly important in insect pest management, particularly for ant, fly, cockroach, and termite control. 12.2.3
Municipal Market
The municipal sector is the smallest of the three and is estimated to be worth in the region of US$ 230 million globally. In this sector government agencies operate in the same way that the PMP does and provide a service of pest management for a municipality or other governmental constituency. Few practical differences actually exist between this and the PPM sector because they have many pests and the methods of pest management in common. In the Municipal sector, however, relatively large-scale programs are usually carried out by the agencies concerned. These are often aimed at the management of disease vectors, but they may also involve nuisance insects where only area-wide programs are likely to succeed. The large-scale of these operations influences the equipment used and, were the production of insecticidal fogs and mists is concerned, space spraying equipment may be vehicle or even airplane mounted. Frequently, Municipal programs utilize biocides in an attempt to prevent or curtail outbreaks of severe human diseases such as malaria, dengue hemorrhagic fever and West Nile virus.
12.3 Rodenticides
The products used in the municipal sector are similar to those used by PMPs. However, applications are often area-wide, and space spraying is a major segment that is found much less frequently elsewhere in the use of biocidal products.
12.3
Rodenticides 12.3.1
Rodenticide compounds
Rodenticides are usually considered in two classes, the acute and the chronic compounds, the latter being exclusively anticoagulants. Another category, the sub-acute compounds, is sometimes also used [3]. The anticoagulants have been the mainstay of chemical rodent control since they were first commercialized more than 50 years ago. Warfarin, the first widely used hydroxycoumarin anticoagulant, revolutionized the practice of rodent control. Up to that point only acute compounds such as zinc phosphide, thallium sulfate and sodium monofluoroacetate (compound 1080) had been available and these suffered several serious disadvantages. Particularly, their efficacy was uncertain and they had no antidotes in the event of accidental poisoning of humans and companion or farm animals. The limited efficacy of this class of compound is due to their rapid mode of action, which leads to rodents sometimes taking only sublethal doses of poisoned baits and becoming “bait shy” (see below). In contrast, warfarin has a delayed mode of action that prevents the development of bait shyness and provided, for the first time, the potential for the complete eradication of rodent infestations. Furthermore, a detailed knowledge of the mode of action of these compounds preceded their introduction as rodenticides and provided a specific antidote, Vitamin K1. Several further anticoagulants compounds were developed and introduced following the success of warfarin. These included diphacinone and chlorophacinone, both indane-dione anticoagulants, and more hydroxycoumarins, such as coumachlor and coumatetralyl [3]. About a decade after their introduction, resistance to the anticoagulant rodenticides was found first in the UK and subsequently became widespread in Europe and, to a lesser extent in North America [4]. The House mouse (Mus musculus/domesticus) had never been particularly susceptible to the warfarin-like compounds and resistance is most extreme in that species. Although, populations of Norway rats (Rattus norvegicus) resistant to warfarin also became widespread. Synthetic chemists set about developing novel rodenticides that could be used to control resistant rodents and, working still with the anticoagulant mode of action, invented a second generation of products, beginning with the introduction of difenacoum and bromadiolone. Later, brodifacoum
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12 Rodenticides and Insecticides Tab. 12.1. The toxicity (acute oral LD50 in mg kg–1) of the five second-generation anticoagulants to warfarin – susceptible strains of the common commensal rodent pest species (from [3]) Compound
R. norvegicus
M. musculus
R. rattus
Difenacoum
1.8
0.8
–
Bromadiolone
1.1–1.8
1.75
–
Brodifacoum
0.22–0.27
0.4
0.65–0.73
Flocoumafen
0.25–0.56
0.79–2.4
1.0–1.8
Difethialone
0.56
1.29
–
and, subsequently, flocoumafen and difethialone were developed (Table 12.1). These five compounds now dominate practical rodent control world-wide, although many of the first-generation compounds remain in use making them some of the most durable compounds used in pest control – either in agriculture or in public health [5]. All anticoagulants possess the same mode of action, that is, they work by interrupting the vitamin K cycle in the liver microsomes. Lacking the blood clotting factors produced by the cycle, poisoned animals are unable to repair the tiny hemorrhages that occur frequently in mammalian tissue and, once a lethal dose has been ingested, die usually of internal blood loss. Since the introduction of the anticoagulants several novel compounds have also come to the market. These are the sub-acute compounds and include the closely related ergo- and chole-calciferol and bromethalin. Although these compounds are in use in some countries, most widely in the USA, they are not as important as anticoagulants in the market because they possess some of the same disadvantages as the earlier acute compounds. However, they are considered by some to have a role to play in resistance management strategies and many authorities also recommend the calciferols for mouse control.
12.3.2
Formulations
The vast majority of rodenticide products are manufactured as baits–mainly based on cereals or cereal derivatives [3]. These formulations serve a principal purpose to present the active ingredients in forms that are readily accepted by rodents and in this they must overcome competition from naturally occurring foodstuffs. The behavior of laboratory rodents in relation to many artificial feeding situations is the subject of a vast literature from psychology studies [e.g. 6]. However, the feeding behavior of wild rodents is not well understood. Neophobia, or new object reaction, is a frequently mentioned consideration [7]. In this, rodents with feeding patterns established on naturally occurring foods are reluctant to sample new ones – of which a rodenticide bait is
12.3 Rodenticides
always necessarily one. R. norvegicus is said to be particularly affected by neophobia, while M. musculus has been found to perform, if anything, in the opposite fashion being attracted to sample novel foods. It is normal in a situation in which a novel food is offered to a R. norvegicus population to see a period of slow increase in bait consumption, as the population first samples and then begins to feed consistently on the bait, followed by a period of more or less steady consumption. However, when the bait contains an anticoagulant rodenticide, a plateau is rarely reached before the rodenticide begins to take effect. Bait-shyness is another notorious condition of rodent infestations in relation to rodenticide baiting. In this, some animals sample a food, for example, a rodenticide bait, which rapidly has an adverse but not lethal effect. If the onset of this effect is sufficiently temporally close to the sampling of the novel food, the animals concerned are able to relate the unpleasant symptoms to the bait that caused them and refuse to take it again [7]. This occurs frequently when acute rodenticides are used without pre-baiting – that is the application of the unpoisoned bait base for a period of time (see below). As well as providing an attractive food for rodents, rodenticide bait formulations also serve several other functions. Wax blocks manufactured with a hole in them allow the baits to be secured inside rodent bait stations, thus providing an important safety feature. It is this feature that has caused, in the last few years, a significant shift away from particulate baits, such as pellets and granular products, towards block baits. Baits may be left in bait boxes for considerable periods, awaiting sampling and consumption by rodents, and in this case formulations may be adapted to offer protection to the cereal components to prevent moulding or other deterioration. The range of alternative rodenticide formulations is somewhat restricted. It includes contact dusts, which act by rodents taking in while grooming a lethal dose of the poison that has contaminated their bodies, and powders (presented as tablets or in particulate form) that generate poisonous gases. For various environmental, human safety and commercial reasons the use of these products is in decline. 12.3.3
Methods of Application and Patterns of Use
The neophobic response of some rodent species, in particular R. norvegicus, means that acute poisons usually cannot effectively be applied directly. Instead the practice of prebaiting is employed in which the bait base, later to be used to carry the poison, is first offered without poison. The rodents overcome their neophobia of the novel food during this period and eventually consume substantial quantities during feeding bouts. When the poison is added, the familiarity of the rodents with the food results in a greater likelihood of their taking a sufficient dose to be lethal. However, even when applied by experienced practitioners, with pre-baiting, acute poisons rarely achieve
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efficacy of more than 80 % [8]. For this reason the practical use of these compounds is often restricted to certain situations, such as in the control of rodent populations resistant to anticoagulants where, for other reasons, effective second-generation compounds cannot be used. Furthermore, the application of pre-baiting assumes the availability of acute poisons in concentrated form for admixture to baits. For reasons of safety and efficacy, this is increasingly the province of only the skilled pest management professional. Some acute rodenticides are, however, available in ready-to-use form. In this case, the baits are either used without pre-baiting (indeed commercial claims are made that some products do not induce bait-shyness) or a pre-bait material is used that is as similar as possible to the bait matrix. Applications of acute poisons are usually restricted to just a few days because bait-shyness means that rodents are unlikely to take baits even when they are available for longer periods. It is unnecessary to use pre-baiting with anticoagulants because their delayed action means that, in effect, they serve as their own pre-baits. However, a new and important consideration comes into play with their use–that is the requirement for the target rodents to feed repeatedly from the bait for several days for a lethal dose to be acquired. The technique of surplus, or saturation, baiting was developed to ensure that rodents always found bait available when they visited baiting points and consequently readily acquired lethal doses of rodenticide [3]. In this, bait placements are set out that are either initially large enough to allow rodents to feed for the duration of the treatment without running out or are replenished frequently to ensure the same effect. This is necessarily an expensive, time-consuming and potentially wasteful procedure. Initially, the second-generation anticoagulants were used in the same way and the benefits of their use were therefore mainly restricted to areas where resistance to the earlier compounds had developed. However, the intrinsically higher potency of these compounds was soon recognized and this resulted in the adoption of a new baiting strategy – pulsed baiting [9]. Laboratory work showed that baits containing compounds such as brodifacoum were potentially lethal to rodents that took them during only a single feeding bout in which, for rats, just a few grammes were consumed. The difficulty during field treatments lay, therefore, in preventing rodents that had already consumed a lethal dose from consuming further bait during the period of delayed effect that is common to all anticoagulants. In pulsed baiting, relatively small quantities of bait are put out at baiting points that are quickly completely consumed by the rodents, so that poisoned animals returning to bait points find them empty. Subsequent “pulses” of bait are applied only after it is judged that those animals that took a lethal dose from the previous ones have succumbed. This baiting strategy is now an integral part of the labeled patterns of use of all potent second-generation anticoagulants. Its use confers not only the obvious advantage of cost-effectiveness but also improved safety. Less bait is exposed to potential consumption by non-target animals
12.3 Rodenticides
(i.e. reduced primary hazard) and the bodies of poisoned rodents carry lower residues of rodenticide (i.e. reduced secondary hazard). Rodenticide product labels are difficult to write because they must be applicable to such widely varying circumstances as a small mouse infestation in a domestic kitchen to a Norway rat infestation, comprising perhaps several thousand individuals, at a large pig-rearing facility. However, assuming that label recommendations are properly followed, there are several factors that may still result in the failure of practical rodent control treatments. The most common of these is that the size of the infestation is underestimated, either in terms of the number of animals present or the area that they occupy. The consequence of this is that too few bait placements are deployed and the solution is, of course, to add more. Even if the correct number of baits is used they may be in the wrong places. Rats, particularly, establish feeding routines that are sometimes difficult to break, especially if there is an abundance of existing alternative food. It is then necessary to remove, as much as possible, alternative food and to replace this with carefully situated baiting points. Finally, resistance may be the cause of treatment failures. The diagnostic feature of this is that bait continues to be taken over several weeks with little sign of diminution as a result of animals succumbing to the poison (though this may also be a symptom of gross under-baiting). The neophobic response of rats to novel objects in their environment extends beyond food and may include the receptacles used to carry rodenticide baits, such as bait trays and stations. Undoubtedly, the baits most likely to be readily taken by rodents are those placed directly on the ground. However, the use of bait trays is a practice that must be encouraged so that baits are prevented from spilling and can be conveniently removed at the end of treatments. Indoors, if there is no possibility that humans or non-target animals may gain access to rodenticide baits, then trays are all that may be needed by way of protecting the baits. However, this is rarely the case and a wide range of robust bait stations is available that, to varying degrees, protect baits from disturbance and possible consumption by certain non-target animals. Such stations may claim to be “tamper resistant” or “tamper proof” depending on the testing methodology used to demonstrate their effectiveness. When using a good bait station, in conjunction with a bait block that cannot be dislodged from the station, the pest control technician is adopting the safest possible baiting practice. It is to state the obvious, however, to say that while these station go a long way in providing safe rodent control practice they do not prevent access to animals that are the same size or smaller than rats and mice, such as small mammals (mostly rodents) and passerine birds. Also, it should be borne in mind that bait stations undoubtedly adversely affect the uptake of bait by rodents. Recently produced bait station designs claim to have overcome the reluctance of rodents to enter them to feed but the entire area is one that requires further research. When such intense selection pressure is applied so that those rodents that enter bait stations are virtually eliminated, it is obviously to be expected
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that individuals reluctant to enter them will be selected and may come to predominate in populations. Denatonium benzoate (also sold under the trade name “Bitrex”) is a human taste deterrent. This compound is widely used in a variety of household chemical preparations, such as bleaches, detergents, and cleaning fluids. It is now used in many commercial rodenticide baits and has been shown to render them unpalatable to human subjects [10]. The concentration used is dependant on the type of bait in question, most specifically the quantity of sugar or sweetener it contains, and consequently the degree of flavor masking that is required. A concentration of 10 ppm is widely used and has been found to have no adverse effects on bait uptake by rodents. However, more work is required with wild rodents as test animals before substantially higher levels of denatonium benzoate can be used without fear of an adverse effect on efficacy. Once again, with the increasing use of denatonium benzoate in rodenticide baits, selection pressure is high to induce the development of rodent populations containing individuals that reject baits that contain it. At the concentrations used in rodenticide baits, this compound has no effect in preventing accidental bait consumption by companion and farm animals.
12.4
Insecticides 12.4.1
Insecticide Compounds
With a few exceptions, the very wide variety of insecticide compounds available for use in public health pest control has been provided by research and development aimed at the discovery of new products for use in agriculture. The attractiveness of the large crop protection market continues to provide a stream of novel insecticides that, after appropriate evaluation, and sometimes the development of specific formulations, are successfully adapted for use in public health and structural pest control. The range of chemicals used as insecticides is so great, and their number so many, that only a superficial overview can be provided in the sections that follow. However, it is likely that a number of the compounds in common use today will leave the market in Europe as the Biocidal Products Directive (BPD) takes effect over the next decade and as their usefulness is superseded by more modern products. The first widely-used crop protection insecticide, dichloro-diphenyl-trichloroethane (DDT), is now largely withdrawn from such use but is still occasionally used in the control of public health pests, particularly malaria-transmitting mosquitoes. This is a subject of contention and DDT, as well as the rest of the organochlorine (OC) class of compound, which includes aldrin, dieldrin, gamma-HCH, chlordane and endosulfan,
12.4 Insecticides
have been largely withdrawn and superseded by newer chemistries. It seems unlikely that any OC uses will survive the introduction of the BPD in public health pest control in the European Union. The next class of compounds to be introduced in the early 1950’s was the organophosphates (OPs) and many of these compounds remain in current use. Their common mode of action is to inhibit the enzyme acetylcholinesterase, preventing the clearance of acetylcholine at the nerve synapse and resulting in uncontrolled nerve impulse transmission and tetanus. A very large number of OP compounds was developed during the period 1950 to 1975 and many of them found use in public health and structural pest control. Some of the most commonly used compounds include (roughly in order of their introduction): malathion, diazinon, dichlovos, chlopyriphos, acephate, propetamphos, and pirimiphos-methyl. The OPs are contact and stomach-acting insecticides, some with considerable vapor action. Many possess good residual effect and low mammalian toxicity, and are consequently found in almost all sectors of the public health and structural pest control market. Among their drawbacks is that they are often malodorous when used indoors and recovery to exposure in non-target animals is prolonged as it depends on the synthesis of new acetycholinesterase, because binding to the enzyme is irreversible. The mode of action of the carbamate insecticides is similar to that of the OPs, except for the fact that enzyme inhibition is largely reversible. This advantage is offset to some extent by the relatively high mammalian toxicity of these compounds. The principle carbamates used as biocides are propoxur and bendiocarb. These compounds, which also act as contact and stomach poisons, are widely used in pest control. There is good knockdown and flushing of insects, with some residual activity, and bendiocarb is used particularly in aerosols for the control of crawling insects, such as cockroaches. These first three classes of insecticide, although still in use to varying degrees, are now less favored for several reasons. Resistance to some compounds is now widespread and newer compounds have been developed with better toxicological and environmental profiles, as well as with excellent spectrums of activity, including an ability to control insects that are resistant to the earlier compounds. The first of these new insecticide groups was the pyrethroids. About the time that the OPs were being introduced, the insecticidal properties of a series of naturally occurring compounds, the pyrethrins, were recognized. However, both when based on natural extracts and when synthesized, these compounds were found to be photolabile. It was only in the 1970’s, with the introduction of the UVstable synthetic pyrethroids, that this mode of action could be fully exploited commercially [11]. Like the earlier compounds, pyrethroids act on insect neural pathways, but in this case the mode of action is to block sodium channels, leading to uncontrolled axon excitation and death. This new class of chemistry had advantages of low mammalian toxicity, (sometimes) long residual effect, rapid action, broad spectrum, low
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12 Rodenticides and Insecticides Tab. 12.2. Relative toxicities of some insecticides to key public health insect pests by topical application (adapted from [11]) Compound
Musca domestica
Periplaneta americana
Glossina austeni
Anopheles stephensi
Natural pyrethrins
2
100
20
Bioallethrin
6
150
–
–
Tetramethrin
2
–
–
31
Bioresmethrin Permethrin
14
100
100
100
100
60
290
87
100
Cypermethrin
210
–
350
520
Deltamethrin
1500
3000
3300
3100
38
200
31
74 2400
Fenvalerate Lambda-cyhalothrin
1500
5000
2200
DDT
12
15
3
2
Dieldrin
20
10
26
27
Carbaryl
–
–
<5
14
Malathion
1
–
<2
14
usage rates and low odor. These properties resulted in the rapid adoption of synthetic pyrethroids in all fields of public health pest control, including domestic and commercial aerosols, flying insect coils and mats, space sprays and thermal fogs, residual surface treatments, larviciding, and the treatment of fabrics such as bed-nets and clothing [11]. More than forty years of research and development has provided in excess of 30 synthetic pyrethroids with a wide range of properties. The efficacy of some of these compounds against key public health pests is shown in Table 12.2. Probably the most widely used of these compounds are tetramethrin, permethrin, cypermethrin, deltamethrin, alpha-cypermethrin, cyfluthrin, bifenthrin, and lambda-cyhalothrin. Knockdown agents in aerosols are almost exclusively pyrethroids. The insect growth regulators (IGRs) are a varied group of compounds involving many different chemical classes. As their name suggests, all act to impair the growth process in insects, in particular the moulting of the exoskeleton, and since this is unique to arthropods many offer a high degree of target specificity. There are two major IGR classes. The first type to be introduced was the juvenile hormone analogues (or mimics), which includes the compounds methoprene and hydroprene [12]. Later, another chemical class was invented, the benzoylureas, which act by inhibition of the enzyme chitin synthetase. Compounds in this class include diflubenzuron, triflumuron, hexaflumuron, chlorfluazuron, flufenoxuron, and lufenuron. Other IGRs with different chemistries are pyriproxyfen, a juvenoid, and fenoxycarb, a carbamate with an IGR mode of action. The IGRs are used extensively in public health
12.4 Insecticides
pest control as surface sprays but their slow speed of effect makes them particularly useful in baits for ants, flies, cockroaches and termites. For much of the latter half of the twentieth century the compounds described in the preceding paragraphs were the principle insecticides used in public health. However, the last decade has seen the introduction of a number compounds, belonging to new chemical classes, with properties that make them particularly suited to public health uses. Among the first of these was fipronil, a phenylpyrazole, which acts in insects to block the GABA-regulated chloride channel in the nerve axon. Fipronil, a broad spectrum insecticide with contact and stomach action, is widely used in baits, as surface sprays for the control of the important public heath insect pests and in termite control. Another new class is the neonicitinoids whose most widely used member, imidachloprid, is increasingly applied for general pest and termite control. Once again these compounds act on the insect nervous system, this time by preventing the transmission of nerve impulses by competing with acetylcholine for binding sites on the postsynaptic membrane. Further interesting compounds such as chlorfenapyr and thiamethoxam are under development from similar chemical series. Resistance to insecticides is a subject that creates a great deal of discussion among manufacturers, researchers, pest control practitioners and regulators. Classical definitions usually involve the identification of an insect strain that is measurably less susceptible to a compound than a reference strain. However, such resistance, when identified, offers little indication of the practical importance of the observation. In rodenticides, a distinction between technical resistance and practical resistance has been proposed [13] and such discrimination may be more widely valuable. The incidence of resistance among pest insect groups is varied. Those with very short periods between generations, such as flies (Musca spp.) and the German cockroach (Blattella germanica), tend to develop resistance to insecticides more readily than others such as the social insects (ants and termites) where the reproductives are rarely directly exposed to insecticides and generation times may be very long. However, resistance is now such a widespread and well-recognized phenomenon that resistance management strategies are the subject of much research. They are also an integral part of insecticide patterns of use and product labels and may be advocated even at the start of the life of a product in the market place.
12.4.2
Formulations
With very few exceptions, insecticides are not applied as technical active ingredients but are first modified by some kind of formulation process before being used by pest control practitioners. The variety of insecticide formulations is almost as wide as the
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range of active ingredients they contain and, once again, only those used most commonly will be discussed here [14]. Different formulation types have different advantages but most serve both to facilitate handling and accurate measurement of insecticides and to reduce their toxicity by being of substantially lower concentration than the technical active ingredient. Many insecticides are commonly used as Emulsifiable Concentrates (ECs). These are liquids in which the technical is dispersed in a solvent system, usually based on organic solvents, which also contains emulsifying agents. When added to water, with some agitation, a water/organic solvent emulsion is produced which can be applied through compression spraying and many other types of equipment. ECs produce rapid effects. They are used as sprays outdoors and indoors, for flushing and knock-down. However, they have little residual effect, are sometimes malodorous, are absorbed into porous surfaces and rendered ineffective, and may damage polished or painted interior surfaces and plant flowers and foliage. For these reasons, and because they are based on organic solvents, they are being replaced by other, more advanced formulations. Wettable Powders (WPs) are also commonly used, most frequently by PMPs for pest control around homes and businesses and by municipalities for the control of insect vectors of disease. In these formulations, the active ingredient is presented as a dry, powder with a carrier, usually a finely particulate, inert, mineral dust, and a wetter that promotes the dispersion of the formulation in water. WPs are favored because they are capable of giving long residual effect and of resisting the adverse effects of aggressive surface substrates, such as highly alkaline concrete and aggregate blocks. However, these fine powders can become airborne during measurement and handling; a disadvantage that is overcome when they are packed in unit-dose soluble sachets. WPs require more agitation than ECs in order to get them into, and to keep them in, suspension and may leave undesirable visible deposits on some surfaces. Another liquid formulation is the microcapsule or Capsule Suspension (CS). These are increasingly popular as they overcome many of the disadvantages of the formulations discussed previously. There are several different manufacturing processes used to produce CS formulations [15]. Generally, the active ingredient is dissolved in an organic solvent medium and broken into very small droplets that, at the next stage of manufacture, become surrounded by capsule walls of differing structures. The capsules are held in suspension in a water-based medium, which forms the main bulk of the product. CS formulations are therefore based on water rather than organic solvents and, consequently, possess good toxicological profiles. They are easy to handle and mix and their properties, in terms of efficacy against different insect pests and longevity of residual effect can be manipulated depending on the size of the capsules, the nature of the capsule walls and the active ingredient they contain. Somewhat similar to CSs are suspension concentrates (SCs). In these formulations, often produced to present as
12.4 Insecticides Tab. 12.3.
Classification of sprays by droplet size (from [16])
Type of Droplet
Volume Moment Diameter (lm)
Fine aerosol (or fog)
<25
Coarse aerosol
25 – 50
Mist
50 – 100
Fine spray
100 – 200
Medium spray
200 – 300
Coarse spray
>300
liquids active ingredients that are relatively insoluble, solid particles are prevented from settling out by suspension agents. Their liquid phases are based either on water or organic solvents. Of course, there is no capsule wall in the case of an SC and the performance of the product is determined by the nature of the (once suspended) particle when it is deposited on the substrate. The term aerosol refers to very fine airborne particles, usually of liquids but sometimes solids, having a particle volume moment diameter (VMD) of less than 50 lm (Table 12.3). Insecticide aerosols are most commonly used in the consumer retail insect control sector, though they are also used in other fields, and are mostly produced from specially designed disposable canisters. In an aerosol canister, the active ingredient is dispersed in an organic solvent and packed under pressure together with a propellant. A nozzle valve, with a pressure release mechanism, is used to control the expulsion of the contained formulation from the can so as to form the aerosol droplets. The droplet VMD of the aerosol is modified by the engineering characteristics of the nozzle and valve. Usually, fine aerosols are used in FIKs to allow them to remain suspended in the air for some time in order to kill flying insects. Coarser aerosols are used for CIKs that are applied to surfaces for the control of pests such as cockroaches. Very coarse sprays, directed from the aerosol nozzle through a narrow bore tube, are used for the treatment of insects harboring in cracks and crevices. Some aerosols contain CS formulations for application to exterior surfaces to form barriers to prevent insects resting near and entering the home. Solid insecticide formulations are also used, perhaps the simplest of which are the dusts. These are usually based on mineral inerts and, of course, are applied directly without wetting. If they remain dry they provide long residual effect and they may be propelled by application equipment into inaccessible areas, such as roof and wall voids. The insects themselves may also carry them about. This mobility is, however, also a disadvantage in that they may be carried into places where they are not wanted, such as food storage and preparation areas. This is largely overcome by granular formulations, in which dusts are aggregated to form small pellets or granules that are treated, by impregnation or coating, with insecticides.
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Insecticidal bait products have probably provided the biggest revolution in insect pest control in the last decade. These take a variety of forms including pellets, granules, gels, pastes and powders and are widely used for the control of many household pests such as ants, cockroaches, and flies. They cannot be used against insects that feed solely on liquids such as mosquitoes, fleas, and bedbugs. Baits may be applied directly onto the substrate on which the insects are crawling or from bait stations that are purchased already charged with bait or may be charged using special bait dispensers. The technology of bait manufacture is complex. They must be eaten by insects in preference to often abundant alternative food, and may contain feeding attractants to increase the likelihood of this happening. They must be capable of retaining their attractiveness when stored prior to use and for considerable periods after application. Gel baits are often applied to vertical surfaces, so they must not run nor must they be hygroscopic so that their viscosity changes and causes them to do so. They must also not desiccate, as this will adversely affect attractiveness to insects. The slow-acting insecticides, such as the IGRs and some of the new, stomach acting compounds, are particularly appropriate for use in baits. Most recently some of these have been used as termite baits when impregnated into blocks of wood and other reconstituted cellulosic material, such as cardboard. A number of other formulations may carry insecticides including, tablets, lacquers, paints, foams, polishes, soluble powders, chalks, oils and fumigant powders, and gases. Fumigation is a very specialized field of pest control usually undertaken, mainly but not exclusively for the control of insects, by companies that are particularly skilled in the use of these formulations [17].
12.4.3
Methods of Application, Equipment, and Patterns of Use
Insecticide formulations are produced with the objective of easy, accurate and safe application. Because of these essential requirements, those sold in a ready to use format predominate in the consumer retails market sector. Such products include aerosols, baits, coils, mats and pre-filled trigger sprays, which rely on air pressure derived from a hand pump to propel liquid though a nozzle as a coarse spray. Many of these are also used in the PPM and Municipal sectors but in these the variety of application technologies is even wider [18]. Briefly, these are: Compressed air sprayers: This is probably still the most common insecticide application technique by which practitioners apply formulations, such as ECs, WPs, CSs, and SCs, as liquid sprays comprising droplets with VMD >100 lm. Different types of spray (coarse, fine, flat fan, hollow cone, full cone, crack and crevice jet, etc.) are employed and produced by nozzles of various designs. The main purpose of this technique is to apply a specified quantity of the active ingredient to a known area of treated substrate
12.4 Insecticides
in order to control insects either by direct contact or via a residual deposit. The compressed air may be supplied to the sprayer either by a hand pump mounted within the spray tank or, via a valve, from an external source. Cold fogging and thermal fogging: These machines produce very fine aerosol droplets that have a VMD <50 lm, and become airborne to carry insecticide to control insects that are either flying or resting on interior or exterior surfaces. The efficacy of these treatments is dependent on droplet size; those that are too large quickly fall from the air and those that are too small fail to impact on the target insects [16]. Machines are available which are hand-held, mounted on knapsacks, and on vehicles and aircraft. These, of course, vary considerably in their output and in the areas that can be treated in a given time period. Mistblowers: These machines produce droplets that are intermediate in size between spays and aerosols (i.e. 50 – 100 lm). They are used when a residual deposit is required on surfaces that are difficult or too time-consuming to access with compression sprayers. Aerosols tend to follow airstreams around objects and are inefficient in producing consistent deposits on surfaces and in this case the larger droplets produced by mistblowers are used. As in the case of foggers, mistblowers are available in a wide variety of forms and with different power outputs. Liquid pumping systems: Relatively large volumes of liquid insecticides are used in the exterior treatment of premises for nuisance insect control – so-called perimeter treatments. Such treatments are generally conducted using knapsack sprayers powered by a lever-operated manual pump. Even greater volumes are used in pre- and post-construction treatments for subterranean termites and these are delivered to the spray head by electrically powered pumps that are often vehicle-mounted. Bait application equipment: It is important when applying paste and gel baits to deliver the correct quantity at each baiting point. When the bait is a gel this is conveniently done using a ’bait gun’ that is a syringe-like apparatus. These vary in design and some allow variable amounts of bait to be delivered via graduated settings. Some are disposable, while others are re-usable and allow bait “cartridges” to be mounted in them. Dusting equipment: Applications of dusts can be made using simple hand-held devices that work on a bellows principle. For example, these are used to inject small quantities of insecticidal dusts into termite galleries in wooden structures. There are also a variety of motorized dusting machines and some mistblowers are capable of adaptation to allow them to be used to apply powders. Granules may be applied by hand or machinery normally used for the application of granular fertilizers can be modified to apply insecticide granules. Personal protective equipment (PPE): Generally most rodenticide baits are applied with simple PPE such as gloves and overalls because they should not contain particles that can become airborne and be respired. However, the purpose of many insecticide
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applications is to create airborne droplets and particles and, therefore, a very wide range of PPE is available [19]. Particularly important are respirators and clothing which provides the necessary degree of impermeability to dusts and liquids. Care is required in the operation of machines that produce fogs and mists so at to minimize the proportions of respirable particles (generally <10 lm) that are produced.
12.5
Conclusions
The last decade has seen considerable change in the way that we conduct urban pest control. Almost all of the changes have been for the better. Products are more efficacious, better targeted at the pests they seek to control and create less risk to those applying them, those inhabiting the places where they are used and, generally, to the environment. The future would appear to be quite different, however, for the two groups of products, the insecticides and rodenticides, which are dealt with in this chapter. For the insecticides, there appears to be an almost constant stream of new chemistry to provide novel products for the pest control industry. However, this may be both a benefit and a threat. As new products come to the market the companies that develop them invest large sums of money in the dossiers of data required to register them. There is little doubt that many of the older compounds, replaced in agriculture but for a variety of reasons still useful in urban pest control, will leave the market as it becomes no longer cost effective to modernize the dossiers on which their registrations are based. Nevertheless, novel chemistry, as well as research on biological control agents and in manipulating the genetics of the pests themselves [20], is likely to ensure a stream of innovation in insect pest management for the future. The situation is rather different in the case of the rodenticides. Almost a decade ago it was foreseen that the five second-generation anticoagulants would dominate rodent control for the foreseeable future [5]. Novel rodenticide active ingredients seem no nearer now than they were then. The lack of a substantial market for rodenticides in agriculture, as well as the fact that the efficacy of the current compounds is difficult to improve upon, has meant that there is little incentive to develop new molecules. Advances have been limited to the development of new bait formulations and to improved safety brought about by the introduction of “Bitrex” and the wider use of baiting stations. Generally, current rodent control products and practices seem adequate for the challenges that rodents present in most urban environments. However, the situation in some parts of the UK possibly presages wider problems. Resistance to anticoagulants in the House mouse is widespread, and some populations seem refractive to almost any control measure, both chemical and physical, employed against them.
References
Also, infestations of Norway rats are present on farms in some areas that are resistant in practical terms to the less potent second-generation anticoagulants difenacoum and bromadiolone. Although the more potent compounds would likely be effective against them, their use out of doors is prohibited and management programs have had to fall back on time-consuming and old-fashioned methods such as the use of acute rodenticides, with long pre-baiting, and trapping. It would seem that, if this situation becomes more widespread, the ingenuity of pest controllers, and the patience of those beset by rodent problems, will continue to be tested until novel control measures can be developed and introduced.
References
References
[1] J.T. Snelson, Grain Protectants, Australian Centre for International Agricultural Research, Canberra, Australia, 1987, p.448. [2] N. G. Gratz, Urbanization, Arthropod and Rodent Pests and Human Health, in Proceedings of the 3rd International Conference on Urban Pests, eds. W.H. Robinson, F. Rettich, G.W. Rambo, 19-22 July 1999, Prague, Czech Republic. pp.51 – 58. [3] A.P. Buckle, Rodent Control Methods: Chemical, in Rodent Pests and Their Control, eds. A.P. Buckle, R.H. Smith, CAB International, Wallingford, UK, 1993, pp. 127 – 160. [4] J.H. Greaves, Resistance to Anticoagulant Rodenticides, in Rodent Pests and Their Control, eds. A.P. Buckle, R.H. Smith, CAB International, Wallingford, UK, 1993, pp.197 – 217. [5] M.R. Hadler, A.P. Buckle, Forty Five Years of Anticoagulant Rodenticides – Past, Present, and Future Trends, in Proceedings of Fifteenth Vertebrate Pest Conference, Newport Beach, California, USA, 3-5 March, 1992, pp.149 – 155. [6] M. Domjan, The Principles of Learning and Behavior, Brooks/Cole Publishing, Brooks Grove, California, USA, 1993, p.459. [7] D.W. Macdonald, M.G.P. Fenn, The Natural History of Rodents: Preadaptations to Pestilence, in Rodent Pests and Their Control, eds. A.P. Buckle, R.H. Smith, CAB International, Wallingford, UK, 1993, pp.1 – 21.
[8] B.D. Rennison, A Comparative Field Trial, Conducted without Pre-Baiting, of the Rodenticides Zinc Phosphide, Thallium Sulfate, and Gophacide against Rattus norvegicus, Journal of Hygiene, Cambridge 1976, 77, 55 – 62. [9] A.C. Dubock, Pulsed Baiting – A New Technique for High Potency, Slow Acting Rodenticides, in Proceedings of a Conference on the Organisation and Practice of Vertebrate Pest Control, Elvetham Hall, U.K., 30 August–3 September, 1982, pp.105 – 142. [10] D.E. Kaukeinen, A.P. Buckle, Evaluations of Aversive Agents to Increase the Selectivity of Rodenticides, with Emphasis on Denatonium Benzoate (Bitrex) Bittering Agent, in Proceedings of Fifteenth Vertebrate Pest Conference, Newport Beach, California, USA, 3-5 March, 1992, pp.149 – 155. [11] M. Elliott, The Pyrethroids: Early Discovery, Recent Advances and the Future, in The Pyrethroid Insecticides a Scientific Advance for Human Welfare?, Society of Chemical Industry, Pesticides Science, 1989, 27, 337 – 351. [12] K. Slama, The History and Current Status of the Juvenoids, in Proceedings of the 3rd International Conference on Urban Pests, eds W.H. Robinson, F. Rettich, G.W. Rambo, 19-22 July 1999, Prague, Czech Republic. pp.9 – 25.
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12 Rodenticides and Insecticides [13] C.V. Prescott, A.P. Buckle, Resistance Test Methodologies–A Novel Test Procedure for the Potent Second-Generation Anticoagulants, in Rodent Biology and Management, ACIAR Technical Reports No. 45, 1999, Canberra, Australia, p.82. [14] G. Braness, Insecticides Used in Pest Control, in Handbook of Pest Control, ed A. Mallis, Mallis Handbook and Technical Training Company, USA, 1997, pp.1060 – 1101. [15] P.J. Wege, M.A. Hoppe´, A.F. Bywater, S.D. Weeks, T.S. Gallo, A Microencapsulated Formulation of Lambda-Cyhalothrin, in Proceedings of the 3rd International Conference on Urban Pests, (eds W.H. Robinson, F. Rettich, G.W. Rambo), 19-22 July 1999, Prague, Czech Republic, pp.301 – 310. [16] Anonymous, Equipment for Vector Control, World Health Organization, Geneva, Switzerland, 1990, p.310.
[17] D.K. Mueller, Fumigation, in Handbook of Pest Control, ed A. Mallis, Mallis Handbook and Technical Training Company, USA, 1997, pp.1102 – 1152. [18] E.J. Snell, Equipment, in Handbook of Pest Control, ed A. Mallis, Mallis Handbook and Technical Training Company, USA, 1997, pp.1186 – 1246. [19] J. Laughlin, Protective Clothing for Professional Pesticide Users, in Proceedings of the 2nd International Conference on Urban Pests, ed K.B. Wildey, 7 – 10 July 1996, Edinburgh, Scotland. pp.45 – 56. [20] J.M. Crampton, Prospects for Genetic Manipulation of Insect Vectors as a Strategy for the Control of Vector-Borne Disease, in Proceedings of the 2nd International Conference on Urban Pests, ed K.B. Wildey, 7 – 10 July 1996, Edinburgh, Scotland. pp.1 – 9.
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Antifoulants and Marine Biocides Carol Mackie and Graham Lloyd
13.1.
Introduction
Ever since man took to the water in boats some form of chemical treatment has been necessary to help prevent unwanted fouling of the underwater part of the hull. Fouling is not only unsightly and damaging it also has a serious adverse effect on the operating costs of the shipping companies. It has been estimated that the shipping industry would need an extra 70.6 million tonnes of fuel if antifoulings were not used. This level of increase would contribute 201 million tonnes of carbon dioxide and 5.6 million tonnes of sulfur dioxide to the atmosphere [1] at a time when governments are seeking reductions in environmental pollution. Over the years we have seen a dramatic increase in the regulatory control exerted upon the chemicals industry, much of which is aimed at manufacture, supply and use of chemicals in general. However there are other regulations where the control is aimed at specific uses e.g. pesticides, cosmetics, medicines, and industrial biocides; it is in the latter category that the active ingredients necessary for an antifouling paint to be effective resides. Approval of industrial biocides has been a requirement in several countries for many years with some counties such as the USA, the Netherlands, and Belgium requiring the registration of biocides for almost all use patterns whilst others including the UK, Denmark, Finland, and Sweden requiring approval in a limited number of applications. Countries with schemes for the assessment and approval of biocides used in antifoulants include the UK, USA, Canada, Sweden, the Netherlands, New Zealand, Australia, and the EU with the introduction of the Biocidal Products Directive [2] concerning the placing of biocidal products on the market. There are also moves on behalf of Japan and Korea to introduce recognized regulatory processes for biocides including antifoulants although these are still at a relatively early stage in their development. More recently Finland extended their registration program The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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to include antifouling paints. The program closely follows that put forward for the EU Biocidal Products Directive with a cut off date of 1st January 2001. March 2002 saw the first real milestone with the Biocidal Products Directive (BPD) when companies had to either identify or notify the actives they intend to support through the registration process. On a global scale the International Maritime Organization (IMO) who, following extensive concerns over adverse environment effects caused by the use of the organotin, issued a document in November 2001 entitled. The International Convention on the Control of Harmful Anti-fouling Systems on Ships [3]. It is the intention of this convention to ban any new applications of organotin based antifouling paints from January 1st 2003 and to ban its use on all ships after 2008. Concern about problems caused by organotin has resulted in a closer scrutiny of the regulatory procedures by regulating authorities with a subsequent tightening of the acceptance criteria.
13.2
Uses for Antifoulants
In terms of volume the major use for antifoulants is in the prevention of fouling on yachts, boats and ships. Other important areas include use on navigation and marker buoys, fishing nets and fish cages, and offshore structures. Failure to use an antifoulant causes increased drag leading to a decrease in speed, increased fuel consumption, and high service and cleaning costs.
13.3
What Type of Organisms Are Found
Although there are over 4000 organisms that can cause biofouling they can be divided into two groups, micro-organisms such as bacteria and algae that are first to colonize a surface, and the macrofouling species e.g. barnacles, tubeworms, limpets, and seaweeds that follow on. All contribute the problems associated with fouling.
13.4
Types of Antifoulant Used on Ships
Formulation of an antifoulant is dependent on the type of boat or ship on which it is to be used: inshore coastal, ferries, ocean going tankers, fresh water and marine. A major distinction is between ships and yachts where the life of a product to be used on large ocean going ships is up to five years whilst for yachts a coating is typically replaced after one season. A further division is into one of four main types.
13.5 Active Substances Used in Antifouling Paints
13.4.1
Soluble Matrix
This is relatively old technology. It is a soluble matrix of rosin that has low solubility in seawater allowing a slow release of any biocide contained within the rosin matrix. This process continues until the film is eventually exhausted. Products based on this technology typically exhibit a biocide release rate curve that decays exponentially.
13.4.2
Insoluble Matrix
Here the biocide is mixed into an insoluble matrix which is then released by dissolution when in contact with the sea. Initially there is a high release rate of biocide which decreases exponentially with time leaving behind the matrix as a honeycomb structure at the paint surface. A high mechanical strength is obtained with this type of coating.
13.4.3
TBT Self Polishing Copolymer
With this type biocide, TBT is chemically bound to a methacrylic acid/methylmethacrylate copolymer matrix. Hydrolysis together with physical wearing results in a polishing action that continually exposes a fresh surface layer, releasing biocide into the surrounding water at a predictable rate. TBT self-polishing copolymer has a high mechanical strength, allowing build up of very thick systems.
13.4.4
Ablative (Polishing Copolymer) Tin-free
This type relies on the incorporation of a biocide into a mixture of insoluble polymers together with a soluble medium e.g. a rosin. Biocide is released by physical ablation of the polymer which is less controlled than the chemical ablation making a steady release rate difficult to achieve.
13.5
Active Substances Used in Antifouling Paints
Various lists of active substances have been published and in 1999 the Antifoulant Manufacturers working group of CEPE (Consil Europee´en de I’Industrrie des Peintures, des Encres d’Imprimerie et des Couleurs d’Art), produced a list of those active substances in
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Active substances used in antifouling paints
Chemical Name
Common Name
CAS NO.
dicopper oxide
01317-39-1
Copper metal Cuprous oxide Copper thiocyanate Distannoxane, hexabutyl
0111-67-7 Bis-tributyltin oxide
00056-35-9
dichlofluanid
01085-98-9
Tributyltin copolymer N-(dichlorofluoromethylthio)-N,N’-dimethyl-N’(phenylsulfamide) 4,5-Dichloro-2-n-octylisothiazolin-3-one
dichloroisothiazolone
64359-81-5
2-Methylthio-4-tert-butylamino-6-cyclopropylaminotriazine
Irgarol
28159-98-0
Copper-bis(1-hydrox-2(1H)-pyridinethionato-O-S-)
copper pyrithione
14915-37-8
Zinc-2-pyridinethiol N-oxide
zinc pyrithione
13463-41-8
3-(3,4-Dichlorophenyldimethyl) urea
Diuron
00330-54-1
Dehydroabiethylamine
01446-61-3
2-(Thiocyanomethylthio)benzothiazole
TCMTB
N-(Dichlorofluoromethylthio)phthalimide
Fluorofolpet
00719-96-0
Methanesulfenamide-1,1-dichloro-N-(dimethylamino)sulfonyl1-fluoro-N-4-methylphenyl
Tolylfluanide
00737-27-1
Thiocarbamate
Thiram
Zinc ethylenebis(dithiocarbamate)
Zineb
12122-67-7
1-3-Benzenedicarbonitrile, -2,4,5,6-tetrachloro
Chlorothalonil
01897-45-6
Pyridintriphenylborane
Hokkocide
Manganese ethylenebis(dithiocarbamate) (polymeric) complex with zinc salt
Mancozeb
08018-01-7
Manganese, 1.2-ethanediylbis(carbamodithioato)(2)
Maneb
12427-38-2
use in antifoulants in the EU. Table 13.1 contains a list of active substances used in antifouling paints. It is envisaged that of the active substances listed a number will not be supported through all the increasingly stringent regulatory review procedures.
13.5.1
Copper and Copper Salts
Copper is also one of the essential elements involved in many biochemical reactions in all organisms. There is also a natural background level in the environment. Most is bound to organic matter with less than 0.1 % being bioavailable. Copper is also the backbone of past and present antifoulants. In its active form, Cu2+, it is a very effective biocide exerting its affect at very low concentrations. When formulated into an antifouling paint it will leach out at a controlled rate creating a micro-
13.5 Active Substances Used in Antifouling Paints
Fig. 13.1.
Toxicity/deficiency profile of copper
layer at the paint surface; this then controls or prevents the attachment and subsequent growth of fouling species on the hull. Of all the copper compounds available, copper(I)oxide and copper thiocyanate are the most commonly used. As an essential element, copper has a toxicity/deficiency profile as shown above (Figure 13.1). Copper is ideal for use as an antifouling active substance as it is a naturally-occurring material and is an essential element required for normal growth by all plants and animals. As such it is a normal and essential constituent in the ecosystem in both soil, sediment and water. It is generally agreed that it is the cupric ion, Cu2+, that is most responsible for toxicity. Numerous studies have shown that most of the copper present in marine environment is not present as cupric ion. In fact, the concentration of the cupric ion is an order of magnitude lower than the dissolved or total copper concentration. Most of the dissolved copper is complexed with organic and particulate material in marine and freshwater environments. This reduces or completely removes its bioavailability and therefore toxicity to marine organisms. Sedimentation removes particulate copper complexes from the water column and introduces it into sediment where it becomes tightly bound to organic matter and inorganic compounds. Sediments will be the final sink for all copper in the ocean, both natural and anthropogenic. Copper has a high tendency to become nonavailable also in sediments. Very important in this context is the binding to sulfides. The reaction between copper and sulfides in sediments results in the formation of insoluble inert copper sulfides that are nonbioavailable. Copper, having been through the risk assessment processes in many countries, is an active component in many antifoulant paints and in most countries, approvals have been successfully continued. Although some EU authorities have raised concern over
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copper compounds used in anti-fouling paints, leading to restrictions and/or bans of copper-based anti-fouling paints used in pleasure craft in Sweden and the Netherlands, adverse effects from copper have not actually been observed in either of these perceived highly environmentally-sensitive environments. Indeed, in many European waters where the aquatic life was severely affected by TBT pollution in the 1980’s, recoveries of commercially sensitive species of bivalves have been monitored and confirmed over the past 10 years as TBT-based yacht paints have been replaced with copper-based paints.
13.5.2
Tributyl Tin Oxide
Since its introduction in the early 1970s, TBT has been a very important active substance for use in antifoulants. It is very effective, exerting its effect on many fouling species. Antifoulants made with TBT have given long-term performance, provide good film integrity and due to the time they have been on the market have accumulated a large database of information on their efficacy, toxicity, ecotoxicology, and environmental fate effects. Values for the rate of degradation in the environment range from 1 to < 18 days by photolysis, to aerobic and anaerobic metabolism in soil of <180 days and in seawater 50 to 75 days. This level of persistence in the environment, the bioaccumulative nature of TBT and the toxic effects seen against nontarget species led to a move to restrict and eventually a total ban its use an antifoulant. Most countries now have a restriction on the use of TBT. Japan was the first to impose a ban on the use of TBT whist other countries opted for restricted use, banning application to non-aluminum hulls of vessels less than 25 meters in length and at a maximum release rate limit of <4 lg cm–2 day–1 TBT. More recently Germany and Belgium put forward plans for the introduction of an EU regulation to ban the use of organotin antifoulants and although very much supported by the remaining member states legislative action did not follow. After publication of the IMO Convention in October 2001 it was reported that the EU was to begin consideration of an extension of controls for the use of organotin under the Marketing and Use Directive. In the USA the EPA were to consider legislation to outlaw vessels coated with paints containing TBT [4].
13.5 Active Substances Used in Antifouling Paints
13.5.3
Booster Biocides
The move towards a ban on the use of TBT led to a reliance on the use of copper based antifoulants in association with organic booster biocides to broaden the scope of activity. Development and proving the value of TBT alternatives has proved to be a complex and time consuming procedure. In addition to the development of coatings to satisfy the stringent requirements of the industry, environmental factors are also a major consideration [5]. A number of acceptable TBT alternatives have now demonstrated long-term performance under different fouling conditions and have gained approval by regulatory authorities. As previously referenced there are a number of candidate booster biocides some of which have found greater success than others. 13.5.3.1 4,5-Dichloro-2-n-octyl-isothiazolin-3-one (DCOI) DCOI has a broad spectrum of activity against fouling organisms. An important feature of DCOI is the rapid rate of abiotic and biotic degradation when in seawater (Table 13.2). The resulting metabolites have been shown to be much less toxic to aquatic species than the parent substance [6]. Another feature is the relatively high partition coefficient indicating that DCOI will move out of the water phase and become predominantly associated with the sediment. DCOI has approval for use in a number of countries but is in the main recommended for use on marine shipping and in 1996 was awarded the USA Presidential Green Chemistry award in recognition of its contribution to the protection of the environment.
13.5.3.2 Zinc and Copper Pyrithione
Together with copper oxide, zinc and copper pyrithione have proven to be highly effective in antifoulant paints. Zinc pyrithione has a long history of use in applications
Tab. 13.2.
Summary of environmental fate of DCOIa)
Mechanism of Degradation
Half-life [h]
Abiotic degradation – Hydrolysis
216 – 720
– Photolysis
322
Biotic degradation – Aerobic metabolism
<1.0
– Anaerobic metabolism
<1.0
a) Half-life (the time it takes for 50 % of the parent substance to degrade).
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Summary of environmental fate of zinc and copper pyrithionesa
Mechanism of degradation
Conditions
Half-life Zinc Pyrithione
Half-life Copper Pyrithione
Hydrolysis Artificial seawater
abiotic-no light
>90 days
12.9 days
Hydrolysis Natural seawater
biotic-no light
4 days
4.0 days
Hydrolysis River/pond water
biotic-no light
7–8 h
–
Photolysis
abiotic-Xe lamp
17.5 mins
29.1 mins
Photolysis
abiotic–sunlight
<2 mins
–
Aerobic metabolism
Biotic
2 – 22 h
2 – 22 h
Anaerobic metabolism
Biotic
0.5 h
0.5 h
a Half-life (the time it takes for 50 % of the parent substance to degrade).
other than that as an active substance in antifoulants, whilst copper pyrithione is a relatively new introduction. Studies on both substances to assess their degree of impact on the environment show them to have a rapid rate of degradation in the water column (Table 13.3) via biotic and abiotic pathways leading to the production a series of less toxic metabolites [7]. Modeling predicts that the steady state environmental concentration would remain significantly below the toxic threshold for organisms with a low no observable effect concentration. Approval has been granted for zinc pyrithione in the majority of countries where approval is required with approvals pending in the others. There is also an active program to gain approval for copper pyrithione. 13.5.3.3 4-tert-Butylamino-2-methylthio-6-cyclopropylaminotriazine
By specifically inhibiting the growth of photosynthetic organisms so preventing the attachment of fouling organisms is an important quality of this highly active algaecide. It is effective at low concentrations and has a low water solubility. It has been reported that the rate of degradation by hydrolysis is slow but will undergo photodegradation under solar light with 80 % of the parent degraded in 15 weeks. The rate of degradation in natural seawater and river water was higher than that in pure water [8]. Irgarol has been detected during monitoring studies. It is approved for use in some countries.
13.5 Active Substances Used in Antifouling Paints Tab. 13.4.
Summary of environmental fate of dichlofluanida
Mechanism of Degradation
Half-life (h)
Abiotic degradation – Hydrolysis
<0.2 – 468
– Photolysis
No UV adsorption under sunlight
Biotic degradation – Aerobic metabolism
1.1 – 2.7
– Anaerobic metabolism
1.1 – 2.7
a Half-life (the time it takes for 50 % of the parent substance to degrade).
13.5.3.4 N-(Dichlorofluoromethylthio)-N,N’-dimethyl-N’-phenylsulfamide
Although the main use for this active is in crop protection it has found a niche market in antifoulants, particularly for use on yachts. This active will degrade rapidly when in the aqueous environment so fulfilling a number of important criteria for an acceptable antifouling active substance [4] (See Table 13.4).
13.5.4
Nonchemical Alternatives
In an effort to move away from the use of biocides in antifoulants there has been a move to the development of nonbiocidal antifoulant examples of which are described below. Silicone Elastomers These have a very low surface tension resulting in no water layer adhering to the hull of 13.5.4.1
the ship and so preventing the colonization by sticky bacteria and larvae. To be effective, boats and ships using this type of antifoulant must maintain a speed of at least 15 knots; if in dock for any length of time fouling will occur, however in most cases it can easily be removed with a sponge or a water jet. There are silicone-based products that contain a biocide to combat fouling when in dock. There are no regulatory requirements for the “biocide free” products. 13.5.4.2 Fibers
A coating is made up of millions of micro fibers held onto the surface of the ship by a strong adhesive so imitating the way some marine mammals protect themselves. Each microfibril is electrostatically charged enabling it to stand upright in the adhesive.
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13.5.4.3 Enzymes
This involves the use of hydrolytic enzymes and micro-organisms incorporated into an antifouling coating. This “live” film helps prevent colonization by unwanted species so giving protection to the coated vessel.
13.5.4.4
Aluminum Silicate
This research sponsored by the USA EPA demonstrated the feasibility of developing a waterborne antifouling coating based on aluminate chemistry which exhibits good antifouling properties. Coating produce a hard film that is easy to apply.
13.6
Data Requirements
An acceptable risk assessment result is key to the placing on the market of antifoulants, and key to the risk assessment calculation is the submission of a comprehensive package of data. Over the years the type and amount of data requested by the authorities has changed. With the introduction of the Biocidal Products Directive there is an increased demand for data not only on active substances but also on metabolites and substances of concern used in the formulation. Data required on the paint has also increased with an enhanced focus on exposure scenarios and environmental and worker exposure studies. Antifoulants are one of the few use patterns where the chemicals incorporated into the paint remain in close intimate contact with the aqueous environment for the lifetime of treatment. Because of this the data required to calculate the level of risk differs from that for many other use patterns, with a greater emphasis on the provision of data concerning ecotoxicology and environmental fate.
13.6.1
Data Requirements for an Active Substance According to the EU Biocidal Products Directive
Data required to support an active substance is divided into (see Table 13.5): a) the “common core data set”, this is data necessary to support all active substances regardless of what product types they are to be used in. b) “Additional data set” this is in addition to the core set and is determined by the product type in which the active will be used.
13.6 Data Requirements Tab. 13.5.
Data requirements for an active substance used in an antifouling paint
Company Information
Information about the applicant and the tonnage of active substance to be place on the market per year
Identity of substance
Structure, purity, impurities
Physical and chemical properties
e.g. appearance, density, melting point, solubility, log octanol water partition coefficient, adsorption spectra, thermal stabilityidentification of breakdown products, surface tension, flash point, reactivity to containers
Analytical methods
in pure substance, water, soil, air, body fluids
Efficacy
effectiveness against target organisms, mode of action
Exposure date
environmental, workers, general public
Toxicological and metabolic studies
acute toxicity, metabolism in mammals, repeat dose, chronic toxicity; carcinogenicity, genotoxicity, reproductive toxicity, teratogenicity, fertility, neurotoxicity, mechanistic study
Medical data
health records, epidemiological studies, medical surveillance date, clinical cases,
Poisoning
incidents, diagnosis of poisoning, specific treatment in case of an accident or poisoning, prognosis following poisoning sensitization/allergenicity observations
Toxic effects to
livestock and pets, transfer of toxicity to food and feeding stuffs, identification of residues.
Toxicity of metabolites and degradation products
amount of data is dependent on the level of toxicity
Environmental fate
fate and behavior in water and sediments, biodegradation in seawater, absorption an desorption in water/sediment, rate and route of degradation
Ecotoxicity
freshwater, marine, brackish, sp., bioconcentration, prolonged toxicity to fish, effects on reproduction, and growth on fish and invertebrates-marine and freshwater, bioconcentration, bioaccumulation, effects on sediment dwelling organisms and aquatic plants
Effects on; nontarget organisms.
birds, worms
Measures necessary to protect humans, animals and the environment
methods and precautions concerning handling, use, storage, transport or fire, nature of reaction products, combustion gases, etc., due to fire, emergency measures in case of an accident, destruction, or decontamination following release, waste management of the active substance, neutralization of effects, conditions for controlled discharge
Of particular relevance to this industry is the requirement for the testing of marine and brackish species, bioconcentration and bioaccumulation, and environmental fate in sediments. Another important feature in the risk assessment process is the rate at which an active substance will leach out of the paint film. For antifoulants used on fishnets and cages information concerning the potential for the contamination of foodstuffs is essential.
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13.6.2
Data Requirements for Antifouling Paints
The amount of data to support a finished paint has also increased, with the potential to supply more acute and long term aquatic studies, exposure scenarios, and environmental and worker exposure data.
13.6.3
Leach Rates
Release rates of biocides from antifouling paints are required by a number of regulatory authorities to review/regulate the release of biocides into the aquatic environment. An accurate biocide release rate value is essential when conducting an environmental risk assessment. Leaching rates can be measured using internationally accepted guidelines developed by ASTM or ISO working groups that are listed below (Table 13.6). Leaching rates can also be determined by a calculated method developed by CEPE. This calculation method for the determination of leaching rates is based on the assumption that the total release of biocide can never exceed the amount incorporated into the coating. Both of these methods have their limitations; however the importance of obtaining an accurate leaching rate for the specified lifetime of an active substance within a paint film cannot be over emphasized for several reasons: 1. The leaching rate is the initial step in determining a Predicted Environmental Concentration (PEC) for risk characterization in regulatory risk assessment and is used by the majority of the regulatory authorities for determining whether the active substance in the antifouling product gives rise to an acceptable risk to the aquatic environment. 2. Many regulatory authorities can impose leaching rate restrictions on active substances used in antifouling products, e.g. for TBT the leaching rate is <4 lg cm–2 day–1.
Tab. 13.6.
ASTM or ISO guidelines to measure leach rates
ASTM D5108-90
organotin release rates from A/F coating systems in sea water
ASTM D6442-99
copper release rates from A/F coating systems in seawater
ISO 15181-1
determination of release rate of biocides from A/F paints – general method for extraction of biocides
ISO 15181-2
determination of release rate of biocides from A/F paints – determination of copper-ion concentration in the extract and calculation of the release rate
13.7 What for the Future
13.6.4
Exposure Assessments and Emission Scenarios
As stated above the determination of a Predicted Environmental Concentration is an important factor in determining whether an active substance within an antifouling product will be deemed acceptable to a regulatory authority. There are now several methods going through validation in order to determine the PEC for an active substance and perhaps two of the most important have been recently developed within the EU. In a project commissioned by CEPE and the European Commission, a model (MAM-PEC) was developed to generate PEC’s in the marine environment. This model was developed at the University of Amsterdam and Delft Hydraulics Institute in the Netherlands and determines PEC values for five antifouling product scenarios: 1. 2. 3. 4. 5.
commercial ships in harbors yachts in marinas ships at open sea ships in shipping lanes ships in an estuarine harbor
The model takes into account emission factors (leaching rates, shipping intensities, residence times, ship hull underwater surface areas), compound-related properties and properties and processes related to the specific environment (currents, tides, salinity). A further model has been included that predicts the copper speciation and expected ranges of free Cu2+ ion concentrations [9]. Another environmental model was recently developed by the UK Health and Safety Executive and was used in their recent review of booster biocides used in antifouling paints. This model (REMA) is an estuarine model and predicts the environmental concentrations of active substances used in antifouling products from a multitude of point sources within an estuary. REMA has been developed and based on the Mackay fugacity concept and a quantitative water, air, and sediment interaction model [10]. At present no recognized model is available to predict the human health exposure and emission scenarios from antifouling products.
13.7
What for the Future
The legacy of TBT has led to an increased awareness of what problems can arise if biocides are not thoroughly scrutinized before being allowed on the market. Around the world there is an increase in regulatory activity concerning the use of antifoulants.
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The introduction of the Biocidal Product Directive in the EU and the pending enforcement of the IMO International Convention on the Control of Harmful Anti-fouling Systems on Ships will have a dramatic effect on the industry. The number of actives put forward for approval is set to be reduced considerably as suppliers having carried out a cost benefit analysis decide to pull actives from the market. Factors to be considered include high costs of providing data, uncertainty of success in the review process, and concern about comparative assessment, a process that can remove a product from the market even though it meets the stringent requirements of the risk assessment process. Such factors will also adversely impact on the development of new active substances and products with the inevitable result of a reduced level of choice. Following the publication of the IMO treaty a number of paint suppliers announced plans to push forward with the phase out of TBT base antifoulants and increasing their activity in the production and development of TBT free antifoulants.
References
References
[1] J.E. Hunter, Personal Communication;. International Coatings Ltd, Akzo Nobel. [2] Directive 98/8/EC of the European Parliament and the Council of the 16 February 1998: [3] International Conference on the Control of Harmful Anti-fouling Systems for Ships; 8 October 2000; International Maritime Organisation. [4] Lloyds List; 27th December 2001. [5] Factors to be Considered in the Development of an Antifoulant; G. R.; Lloyd, I. Watt, Tomasgaard, L. Ensus, 2000 Marine Science and Technology for Sustainability, September 4th to September 6th 2000, University of Newcastle upon Tyne, UK. [6] The Environmental Fate of Isothiazolines Biocides, A. Jacobson & T. Williams, Rohm and Haas Company, Chimica Oggi/Chemistry Today; October 2000.
[7] Pyrithiones as Antifoulants: Environmental Chemistry and Preliminary Risk Assessment; P.A. Turley, R.J. Fenn, J.C. Ritter, Arch Biocides Technology. Biofouling, 2000, pp. 174 – 182, Vol. 15(1-3). [8] Okamura et al., Photodegradation of Irgarol 1051 in Water, J. Environ Sci. Health 1999, B34 (2), 225 – 238. [9] Utilization of More “Environmentally Friendly” Antifouling Products, EC Project No, 96/559/3040/DEB/E2. [10] S. Comber, G.S. Franklin, D. Mackay, A.B.A. Boxhall, D. Munro, C.D. Watts, Environmental Modelling of Antifoulants, HSE Contract Research Report 342/2001; 2001.
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Subject Index a Acanthamoebae 245 acaricides 131, 351 acceptable – daily intake (ADI) 160 – operator exposure level (AOEL) 160 active ingredient / substance 49, 81, 326 – 330 – additional data set 335 – 338 – authorization 49 – basic 49, 57, 304, 308 – data requirement 81 – existing 49, 54 – follow-up registration 82 – low risk 49 – new (see there) 49 ADBAC 232 adhesive preservation (see polymer emulsion and adhesive preservation) 243 – 244 adverse effects information 95 – 96 – adverse effect incident 95 – foreign parents or subsidaries 95 advertising 321 aerosol 281 agriculture – Food and Agriculture Organization (FAO) 240 – Institute for Control of Agrochemicals, Ministry of Agriculture (ICAMA) 120 air compartment 168, 182, 363 algae 229 algicide 48, 138 all-in-one-approach 52 aluminium silicate 296 amateur wood preservatives 213 – 214 Ames test – Japan 109 – Korea 116
animal – testing / studies 8, 145, 146 – – ethical issues 8 – welfare 304 Anthrenus flavipes 246 antibiotics 251 anticoagulants 271 antifoulant 130, 132, 287 – 300, 352 – ablative polishing 289 – BPD (biocidal products directive) 288 – copper and copper salts 290 – 292 – data requirements 296 – 299 – insoluble matrix 289 – nonchemical alternatives 295 – 296 – self polishing copolymer 289 – soluble matrix 289 – tributyl tin oxide 292 antimicrobial 75 – 80 – active ingredient 81 – 82 – – data requirement 81 – – follow-up registration 82 – division 76, 80 – pesticides 28, 77 – review time frames 77, 79 – 80 Antimicrobial Reform Technical Corrections Act (ARTCA) 75 – 77 antiseptics 251 approval certificate 120 aquatic compartment 168, 185, 362 arbitration 91 – 92 arsenic 219 – pentoxide 117 Aspergillus niger 246 assessment factor (AF), human health 151, 158 Australia 124 – 128 – early introduction permit 125 – environment program of the commonwealth department of environment 128 – exemption 125
The Biocides Business: Regulation, Safety and Applications. Edited by Derek J. Knight and Mel Cooke Copyright ª 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30366-9
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– low volume chemicals 125 – National Industrial Chemicals Notification and Assessment Scheme (NICNAS) 124 – National Occupational Health and Safety Comission (NOHSC) 124, 127 – National Registration Authority (NRA) 126 – risk assessment 127 – safety data sheet 125 Australian Inventory of Chemical Substances (AICS) 124 authorization 308 avicides 131, 133, 321, 351 azoles 219
b Bacillus – B. anthracis 246 – B. subtilis 246 bacteria, slimicide 226 – 227, 230 – slime-forming 227 – spore-forming 227 basic substance 49, 57, 304, 308 BCDMH 232 Belgium 45, 67 benchmark toxicology, human health 159 – 161 benefit, human health 164 Bhopal disaster 5 bioaccumulation factor 109, 189, 191, 358 biocide / biocidal 1 – definition 307 – industry (see there) 35, 37 – 38 – low-risk 308, 309, 312 – market 27 – 43 – pest control 29, 47, 76, 131, 162, 351 – product (see product, biocidal) 27, 29, 36 – 40, 49, 53, 231, 331 – 334 – public health biocides 251 – regulation 1 – in situ generated 48 – use 1, 4 Biocidal Products Directive (see BPD) Biocide Products for Pest Control (BPPC) 120 bioconcentration factor (BCF) 176, 363 biodegradation 108, 177 – ready biodegradation 179 biological degradation, wood preservative 197 – 200 – aquatic environment 199 – 200 – insects 199 – microbial 198 – 199 – termites 199
bis(tri-n-butyltin) oxide (TBTO) 220 boric acid 219 BPD (Biocidal Products Directive) XV, 2, 21 – 23, 27, 45 – 58, 168, 233, 288, 296, 303 – 365 – Annex I 49, 55, 313, 315, 325 – Annex IIA 53, 57, 325, 326 – 330 – Annex IIB 53, 57, 325, 331 – 334 – Annex IIIA 335 – 338 – Annex IIIB 339 – 340 – Annex IVA 341 – 345 – Annex IVB 345 – 349 – Annex V 47, 350 – 352 – Annex VI 353 – 364 – antifoulants 288 – biocide categories 78 – cost 58 – data requirements 296 – exemptions 306 – history 36 – 40 – human health 161 – product categories 76 – scope 47 – technical notes for guidance (TNG) 49, 51 – US regulatory equivalents 78 Brazil 138 bromide 231 bronopol 232 Bureau – European Chemicals Bureau (ECB) 56, 214 – National Chemicals Bureau, Slovenia 139 Bureau of Standards, South Africa 137 business 4
c California EPA department of pesticide regulation 90 Canada 131 – 135 – Domestic Substances List (DSL) 134 – environmental import regulations 133 – Food and Drugs Act (FDA) 133 – inventory 134 – Nondomestic Substances List (NDSL) 135 – Pest Control Products Act (PCPA) 134 – Pest Management Regulatory Agency (PMRA) 131, 134 – Toxic Substances Control Act (TSCA) 134 – Workplace Hazardous Materials Information System (WHMIS) 135 Canadian Environmental Protection Act (CEPA) 134 cancellation and suspension 97 – cancellation hearings 97
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– emergency suspension 97 – imminent hazards 97 – suspension orders 97 cancer 7 – environmental causes 7 – war on cancer 7 Candida spp. 236 carbamate 219, 277 carcinogenicity, human health 149 CB I 122, 128 cell membrane 231 Center for Food Safety and Applied Nutrition (CFSAN) 76 – 77, 87 Central Europe 140 CEPE (Consil Euroepee´en de l’Industrie des Peintures, des Encres d’Imprimerie et es Coluleurs d’Art) 289 certificate – Confirmation Certificate (CC) 118 – of composition (COC) 118 chemical – Australian Inventory of Chemical Substances (AICS) 124 – Korean – – Chemical Management Association (KCMA) 116, 118 – – Existing Chemicals Inventory (KECI) 116 – manufacture 3 – observational / restricted chemicals, Korea 117 – Philippine Inventory of Chemicals and Chemical Substances (PICCS) 122 – Priority Chemical List (PCL) 123 – Substances Control Law, Japan 104 – 112 – Toxic Chemicals Control Law (TCCL), Korea 115 – 118 Chemical Control Order (CCO) 123 China 120 – 122 – Biocide Products for Pest Control (BPPC) 120 – disinfectants and general biocidal products (DGBP) 120 – 122 – Environmental Management on the First Import of Chemicals (EMFIC) 121 – State Environmental Protection Agency (SEPA) 121 chlorhexidine 255 chlorine 131, 231 – active compounds 256 – – chlorine gas 256 – – hypochlorite solutions 256 chlorofluorocarbon (CFC) 23 cholera epidemic 13
classification 60, 320 – 321 Clostridium botulinum 239 codex alimentarius commission 7, 16 Common Core Data 144, 331 – 334 Common Principles 53, 304, 353 – 364 comparative assessment XVI, 49, 192, 300, 314 competent authority 322 competition / competitiveness, industrial 42 – law 42 confidental/confidentiality 15, 319 – 320 Confidental Business Information (CBI) 118 Consil Euroepee´en de l’Industrie des Peintures, des Encres d’Imprimerie et es Coluleurs d’Art (CEPE) 289 constructional material preservation 237 – 238 – brick 237 – concrete 237 – concrete additives 237 – lichen 237 – stone 237 consumption of biocidal products 30 – 31 – EU by end use 30 – global by region 31 control – Japan, chemical substances control law 104 – 112 – of pest 29, 47, 76, 131, 162 – regulatory control of biocides in Europe 45 – 72 – Toxic Chemicals Control Law (TCCL) 115 – 118 – Toxic Substances Control Act (TSCA) 15 – Toxic Substances and Hazardous Wastes Control Act (TSHWCA), US 122 Control of Pesticides Regulations (COPR), UK 37, 67 cooling – tower, slimicide 229 – water biocides 235 – 236 – – Legionella pneumophila 235 – – non-oxidizing biocides 235 – – oxidizing biocides 235 copper – compounds 219 – and copper salts 290 – 292 – pyrithione 290, 293 core data / data waiving / core data set 53, 145, 296, 326 corporations, large 14 corrosive / corrosivity, human health 147
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cosmetics – and pharmaceutical preservation 236 – 237 – – dermatophytic fungi 236 – – Candida spp. 236 – – Pseudomonas spp. 236 – – Staphylococcus aureus 236 – – Staphylococcus epidermidis 236 – cosmetic directive, EU 237 – Federal Food, Drug, and Cosmetics Act (FFDCA), USA XVI, 7, 75 – 77, 167 – Slovenia 138, 139 cost – effectiveneness 11 – opportunity cost 10 Council of the European Union 303 Council of Ministers 46 cradle-to-grave approach 171 creosote 218 Cryptosporidium parvum 245 cultural theory of risk 9 Czech Republik 140
d dangerous – preparations directive, EU 45, 53 – 54, 60 – 62 – substances directive, EU 45, 60 – 62, 304 – – seventh amendment, EU 45, 67, 304 data – additional data set for active substance 335 – 338 – antifoulant, data requirements 296 – 299 – call-in 92, 94 – – binding arbitration 94 – – Notice of Intent to Suspend (NOIS) 94 – common core data 144 – compensation 89 – 93 – core data, data waiving 145, 296 – EPA’s role 92 – human data 146 – MPD (minimum pre-marketing set of data) 17 – offers to jointly develop data 92 – protection 36, 89 – 93 – – cite-all method 91 – – selective method of citation 91 – requirements 50 – 52 – SIDS (screening information data set) 18 dazomet 232 DBNPA 232 DCDIC 232 DCOI 293
decision – decission-making process 143, 360 – manual 52 – risk management 3 Delaney amendment 7 Denmark 45, 70 Department of Environment and Natural Resources (DENR), Philippines 122 designated substances, Japan 110 – 112, 114 detergent and household product preservation 238 – 239 – antibacterial – – cleaner 238 – – textile wash product 238 – toilet cleaner 238 – washing up liquid 238 developing countries 5 dichloro-diphenyl-trichloroethane (DDT) 276 DIDAC 232 disinfectant 132, 134, 138, 179, 253 – 258, 350 – chlorine active compounds (see there) 256 – design 254 – 255 – efficacy of 264 – 265 – and general biocides XVIII, 29, 47 – phenolic disinfectants 256 – 257 – procedure 253 – 254 – and public health biocides 251 – 265 – – microorganisms 251 – 252 – types of disinfectant 255 Disinfectant and General Biocidal Products (DGBP) 120 – 122 dithiol 232 Domestic Substances List (DSL), Canada 134 dose-response assessment, human health 152 – threshold dose 152 drinking water 13 drug – Federal Food, Drug, and Cosmetics Act (FFDCA), USA XVI, 7, 75 – 77, 167 – Food and Drug Administration, USA (see FDA) 75 – 77, 85, 133
e early introduction permit 125 effects assessment 141 efficacy 359, 364 – wood preservative 222 EHC (Environmental Health Criteria) 18 embalming fluids 134 emission scenario 171 – 173, 299
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endocrine – disrupters 9 – effects 358 end-use product formulations 82 enterprices, small- and medium-sized 40 environment / environmental 353 – Australia 128 – Canadian Environmental Protection Act (CEPA) 134 – compartments 357 – Department of Environment and Natural Resources (DENR), Philippines 122 – exposure assessment 174 – 184 – – environmental behavior 174 – 180 – – environmental concentrations 180 – 184 – import regulations, Canada 133 – National Institute of Environmental Research (NIER), Korea 115, 117 – Predicted Environmental Concentration (see PEC) 54, 190 – 191, 299 – State Environmental Protection Agency (SEPA), China 121 Environmental Antimicrobial Division (EAD) 76 Environmental Health Criteria (EHC) 18 Environmental Management on the First Import of Chemicals (EMFIC), China 121 Environmental Protection Agency (see EPA) 6, 28, 75 – 77 EPA (Environmental Protection Agency), USA 6, 28, 75 – 77 – California EPA Department of Pesticide Regulation 90 – enforcement 98 – – civil penalities 98 – – criminal prosecution 98 EPA – EPA Office Pesticide Programs (OPP) 28, 76 – 77 – EPA Registration Division (ERD) 76 – EPA Special Review and Registration Division (SRRD) 76 ERMA, New Zealand 129 Escherichia coli 239 ethical consideration, human volonteer studies 152 Europe / European – Central Europe 140 – Chemical Industry Federation (CEFIC) 38 – Council of the European Union 303 – EU Biocide Environmental Emission Scenarios (EUBEES) 53 – EU future chemical policy 40
European Chemical Bureau (ECB) 56, 214 European Commission 46, 303 European Crop Protection Association 20 European Inventory of Existing Commercial Chemical Substances (EINECS) 61 European Parliament 46, 303 exemption – formulator’s 82 – from tolerance 84 existing chemical regulation, EU 23, 61 exposure assessment 53, 143, 153 – 157, 168 – 184, 299, 353 – antifoulant (see there) 299 – environmental – – behavior 174 – 180 – – concentrations 180 – 184 – estuarine model 299 – human health 153 – 157 – – characteristics of human exposure 153 – 154 – – consumer exposure 153, 156 – 157 – – external exposure 154 – – indirect exposure 156 – – industrial workers 155 – – internal exposure 154 – – magnitude of exposure 154 – – non-industrial users 155 – – non-professional users 153 – – occupational exposure 154 – 156 – – primary exposure 153 – – private users 156 – – professional users 153 – – residental exposure 156 – – route of exposure 153 – – secondary exposure 153 – reasonably foreseeable misuse 143 – release estimation 171 – 174 – risk assessment (see there) 167 – 193 – transforming and degradation processes 177 – 180 – uses – – by non- professionals 143 – – by professionals 143 – worst-case scenario 143
f FDA (Food and Drug Administration, USA; see also food) 75 – 77, 85, 240 – Canada 133 – Center for Food Safety and Applied Nutrition (CFSAN) 76 – 77, 87 – food additive 76, 85 – 86 – food-contact substances 76, 85 – 86 – – petition for a food additive regulation 86
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– – premarket notification (PMS) 86 – jurisdiction for antimicrobial food-contact uses 85 – Office of Food Additive Safety 76, 87 – pesticide chemical residue 85 Federal Food, Drug and Cosmetic Act (FFDCA), USA XVI, 7, 75 – 77, 167 – Delaney amendment 7 Federal Fungicide, Insecticide and Rodenticide Act (FIFRA), USA XVI, 7, 20, 39, 59, 75 – 77, 167 – registration 39 – re-registration 39 Federal Office of Public Health (BAG), Switzerland 135 film preservative 132 Finland 45, 70 food – contact substance 87 – Federal Food, Drug, and Cosmetics Act (see FFDCA), USA XVI, 7, 75, 77, 167 – Food Quality Protection Act (see FQPA) 8, 75 – 77, 87 – 89 – preservation 239 – 240 – – Clostridium botulinum 239 – – Escherichia coli 239 – – Listeria monocytogenes 239 – – Salmonella spp. 239 – – Shigella spp. 239 – UN Food and Agriculture Organization 16 – World Health Organization (WHO) 240 Food and Agriculture Organization (FAO) 240 Food and Drug Administration (see FDA), USA 75 – 77, 85, 133, 240 formaldehyde 255 formulators – biocidal supply chain, formulators service companies 33 – 34 – exemption 82 FQPA (Food Quality Protection Act), USA 8, 75 – 77, 87 – 89 – risk assessment provisions 87 frame formulation 41, 50, 308 – 309, 360 fuel preservation 240 – 241 – aircraft 240 – ASTM 241 – H2S generation 240 – heating 240 – microbially induced corrosion 240 – power generating 240 – rail 240 – road 240 – ship 240
fungi, slimicide 227 – 228 – moulds 227, 230 – yeast 227 fungicide 341 – 349 – Federal Fungicide, Insecticide and Rodenticide Act (FIFRA) XVI, 7, 20, 39, 59, 75 – 77, 167 – – registration 39 – – re-registration 39 furmecylcox(carboximide) 218
g gas, oil and gas preservation (see there) 242 – 243 genotoxicity, human health 149 – in vitro tests 149 – in vivo methods 149 Giardia lamblia 245 GLP (good laboratory practice) 17, 51, 81, 144 glutaraldehyde 54, 232, 255 green detergent 23 Greenpeace 22 – 23 growth – expected growth of the biocide industry 35 – regulator 48
h harmful organism 28 harmonization 5 hazard identification 3, 10, 141, 144 – 152, 353, 356 – 357 – information gathering 144 – 145 Hazardous Substances Act, South Africa 137 Hazardous Substances and New Organisms (HSNO) Act, New Zealand 128 health, human health / public health (see there) 141 – 165, 251 Health and Safety Guides (HSGs) 18 Henry’s law constant 175, 180 hepatotoxicity 152 household, detergent and household product preservation (see there) 238 – 239 human health / public health 141 – 165, 251 – acute toxic effect 146 – 147 – assessment factor 151 – benchmark toxicology 159 – 161 – benefits 164 – carcinogenicity 149 – corrosivity 147 – data 146 – disinfectant and public health biocides (see there) 251 – 265
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dose-response assessment (see there) 152 exposure assessment (see there) 153 – 157 genotoxicity (see there) 149 hepatotoxicity 152 irritation 147 mechanistic studies 150 medical data (see there) 151 – 152 neurotoxicity 150, 152 no-observed-adverse-effect-level (NOAEL) 142, 158, 355, 356 – personal protecitve equipment (PPE) 155 – probably risk assessment 158 – regulatory decision-making (see there) 161 – 164 – repeated dose toxicity (see there) 148 – 149 – reproductive toxicity 150, 152 – risk – – characterization 157 – 161 – – communication 164 – – risk-benefit analysis 164 – safety margins 158 – 159, 361 – sensitization 147 – threshold exposure levels 157 – 158 – toxicokinetics and metabolism 147 – 148 – volonteer studies, human, ethical consideration 152 Hungary 140 hydrogen peroxide 257 – 259 hydrolysis 177
i identification 56 – hazard 10 IMO (International Maritime Organization) 20 in vitro testing 146 India 138 – safety data sheet 138 industry, biocidal / industrial – competitiveness 38 – costs of compliance 38 – European Chemical Industry Federation (CEFIC) 38 – expected growth 35 – innovation 37 – wood preservatives, industrial 211 – 213 Industrial Safety and Health Law (ISHL), Korea 119 inert ingredients 93 – 94 information gathering 141 insect growth regulators (IGRs) 278 insecticide 131, 267 – 271, 276 – 284, 321, 351 – application methods 282 – 284
– – – – – – – –
bait application equipment 283 compounds 276, 276 compressed air sprayers 282 consumer retail market 268 – 269 crawling insect killers (CIKs) 269 dusting equipment 283 equipment methods 282 – 284 Federal Fungicide, Insecticide and Fodenticide Act (FIFRA), USA XVI, 7, 20, 39, 59, 75 – 77, 167 – flying insect killers (FIKs) 269 – fogging 283 – – cold 283 – – thermal 283 – formulations 279 – 282 – knockdown agents (KDAs) 269 – liquid pumping system 283 – market sign 268 – mistblower 283 – municipal market 270 – 271 – personal protective equipment 283 – professional pest management (PPM) market 269 – resistance 279 – use of patterns 282 – 284 – wood preservative 220 – 221 Institute for Control of Agrochemicals, Ministry of Agriculture (ICAMA), China 120 Intergovernmental Forum on Chemical Safety (IFCS) 19 Interim Status Permit (ISP), Philippines 122 International Maritime Organization (IMO) 20 International Program on Chemical Safety (IPCS) 18 – Environmental Health Criteria (EHC) 18 – Health and Safety Guides (HSGs) 18 Inventory of Existing Chemical Substances in China (IECSC) 122 iodophores 256 irritation, human health 147 isothiazoline 220, 232
j Japan 104 – 115 – biodegradation 108 – Chemical Substance Control Law (CSCL) 104 – 112 – – flow scheme 106 – designated substances 110 – 112, 114 – exemptions from notification 107 – 108 – handbook 105 – hazard communication 113 – 115
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– inventory of existing substances 105 – 107 – low-volume exemption (LVE) 107 – ministries (see there) 105 – poison 114 – safety data sheet 113 – standard notification 108 – 110 Japanese Industrial Safety and Health Law (JSHL) 112 – 113 – flow scheme 112 JUCLID 57
k kathon 232 Korea 115 – 120 – Industrial Safety and Health Law (ISHL) 119 – low volume exemption (LVE) 116 – material safety data sheet (MSDS) 119 – ministry of environment 115 – 118 – ministry of labor toxicity examination 119 – 120 – National Institute of Environmental Research (NIER) 115, 117 – notification requirements 116 – 118 – Toxic Chemicals Control Law (TCCL) 115 – 118 Korean Chemical Management Association (KCMA) 116, 118 Korean Existing Chemicals Inventory (KECI) 116
l labelling 320 – 321 leach rates 298 leather preservation 241 – Aspergillus spp. 241 – Mucor spp. 241 – Penicillium spp. 241 – pickling 241 – Rhizopus nigricans 241 – Trichoderma viride 241 – wet blue 241 Legionella pneumophila 235 letter of access 308, 309, 312, 315 Listeria monocytogenes 239 lowest-observed-adverse-effect-level (LOAEL) 143, 356
m Macedonia 140 mancozeb 290 maneb 290 manual of decissions, EU 30 margins of safety (MOS) 158 – 159, 161
marine biocides (see also antifoulant) 287 – 300 market, biocidal 27 – 43 – development 34 – 36 marketing – and use directive, EU 45, 62 – minimum pre-marketing set of data (MPD) 17 material safety data sheet (MSDS) 119 MBT 232 medical data, human health 151 – 152 – epidemiology 151 – human volunteer studies 151 metalworking fluid preservation 242, 351 – ASTM 242 – microemulsions 242 – oil emulsions 242 – synthetic fluids 242 “me-too” registrations 83 Mexico 138 microbiocides, wood preservative 218 – 220 microcapsule 280 microorganisms 251 – 252, 341 – 349 Ministry of Economy, Trade and Industry (METI, also known as MITI, Japan) 105 – 107, 109 Ministry of Health, Labor, and Welfare (MHLW or MHW, Japan) 105 Ministry of Health and Welfare (MHW) 105 Ministry of Labor (MOL), Japan 105 molluscicides 131, 133, 321, 351 Montreal protocol 62 moulds 227, 230 MPD (minimum pre-marketing set of data) 17 mutual – acceptance of data 17, 28 – recognition 306, 309 – 310 Mycobacterium marinum 245
n Naegleria fowleri 245 NAFTA (North American Free Trade Agreement) 138 National Academy of Sciences (NAS), USA 97 National Chemicals Bureau, Slovenia 139 National Industrial Chemicals Notification and Assessment Scheme (NICNAS), Australia 124 National Institute of Environmental Research (NIER), Korea 115 National Occupational Health and Safety Comission (NOHSC), Australia 124, 127
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National Registration Authority (NRA), Australia 126 Netherlands 45, 64 – 66 neurotoxicity 150, 152 new active – ingredient 80 – – data requirement regulation 80 – 81 – substance 49 New Zealand 128 – 131 – ERMA 129 – Hazardous Substances and New Organisms (HSNO) Act 128 – inventory 129, 130 – pesticides 130 – 131 – toxic substances act (TSA) 128, 129 NIER (National Institute of Environmental Research), Korea 115, 117 Nondomestic Substances List (NDSL) 135 non-target organism 363 no-observed-adverse-effect-level (NOAEL) 142, 158, 355, 356 Nordic council 23 North American Free Trade Agreement (NAFTA) 138 Notice of Arrival of Pesticide and Devices (NOA) 96 Notice of Intent to Suspend (NOIS) 94 notification 57
o observational / restricted chemicals, Korea 117 OECD (Organization for Economic CoOperation and Development) 1 – 3, 16 – 17, 28, 139, 144, 167 – cross reference to OECD product / use types 132 – 133 – harmonization 28 – minimum pre-marketing set of data (MPD) 17 – mutual acceptance of data 17, 28 – principles of good laboratory practice 17 – screening information data set (SIDS) 18 – test guidelines 17 offers to jointly develop data 92 Office of Food Additive Safety 76 oil and gas preservation 242 – 243 – drilling mud 242 – H2S generation 242 – injection waters 242 – sulfate reducing bacteria 242 opportunity cost 10 Ordinance on Environmentally Hazardous Substances (OEHS), Switzerland 136
organism, non-target 363 Organization for Economic Cooperation and Development (see OECD) 1 – 3, 16 – 17, 28, 132 – 133, 139, 144, 167 organo 117, 130 – 131 organophosphates (OPs) 277 Organotin Environmental Program Association (ORTEPA) 20 orthophenylphenol 218 ozone 48
p packaging 320 – 321 papermaking process (see also slimicide) 225 – 226, 232 – paper mill 225 – 226 – pulp 225, 227 – slime-forming bacteria 227 – spore-forming bacteria 227 partition coefficient 174 – 176, 180 patient 24 – protection 4 PEC (Predicted Environmental Concentration) 54, 190 – 191, 299 – PEC / PNEC ratio 190 Penicillium spp. 246 pentachlorophenol (PCP) 211, 219 pentoxide, arsenic 117 percistence / persistent 191, 358 – organic pollutant (POPs) 6, 110 personal protecitve equipment (PPE) 155 pest / pest control 29, 47, 76, 131, 162, 351 – biocide products for pest control (BPPC), China 120 – professional pest management (PPM) market, insecticides 269 Pest Management Regulatory Agency (PMRA), Canada 131 Pest Control Products Act (PCPA), Canada 134 pesticide 28, 76, 136 – antimicrobial 28, 77 – California EPA department of pesticide regulation 90 – chemical residues 84 – 85 – – exemption from tolerance 84 – 85 – – tolerance 84 – Control of Pesticides Regulations (COPR), UK 37, 67 – EPA Office Pesticide Programs (OPP), USA 28, 76 – 77 – export 96 – 97 – – foreign purchaser acknowledgement 97
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– – multilingual translation requirements 96 – import 96 – 97 – inert integredients 93 – 94 – licensing in individual states 98 – New Zealand 130 – 131 – notice of arrival of pesticide and devices (NOA) 96 – re-registration 88 – 89 Pesticide Assessment Guidelines (PAGs) 81 pharmaceutical preservation (see also cosmetics) 236 – 237 phenolic disinfectants 256 – 257 pheromone 48 Philippines 122 – 123 – Department of Environment and Natural Resources (DENR) 122 – Interim Status Permit (ISP) 122 – inventory 122 Philippine Inventory of Chemicals and Chemical Substances (PICCS) 122 photodegradation 177 piscides 131, 133, 351 plant protection products directive, EU 22, 28, 46 – 48 plastic preservation 243 – soil burial 243 – tensile strength 243 PNEC (predicted no effect concentration) 54, 184 – 185, 187 – 191, 358 – PEC / PNEC ratio 190 – uncertainly factors for PNECs 184 – 185 POIDC 232 poison 114 – control 321 – 322 Poland 140 politics / political 11 – institutions 11 pollutant – persistent organic pollutant (POPs) 6, 110 Pollutant Release and Transfer Register (PRTR) 113 polymer emulsion and adhesive preservation 243 – 244 – acrylic – – adhesive 243 – – sealant 243 – animal glue 244 – polyurethane adhesive 243 – silicone sealant 243 – vegetable glue 243 POPs (persistent organic pollutant) 6, 110 practically guidelines 52
Predicted Environmental Concentration (see PEC) 54, 190 – 191 Predicted No Effect Concentration (see PNEC) 54, 184 – 185, 187 – 191, 358 preservation / preservative XVIII, 29, 47, 54, 132, 236 – 246, 251, 350 – 351 – constructional material preservation (see there) 237 – 238 – cosmetics and pharmaceutical preservation (see there) 236 – 237 – detergent and household product preservation (see there) 238 – 239 – film preservative 132 – food preservation (see there) 239 – 240 – fuel preservation (see there) 240 – 241 – leather preservation (see there) 241 – metalworking fluid preservation (see there) 242, 351 – oil and gas preservation (see there) 242 – 243 – plastic preservation (see there) 243 – polymer emulsion and adhesive preservation 243 – 244 – selection 234 – swimming pool and spa treatments (see there) 245 – 246 – surface coating preservation (see there) 244 – 245 – textile preservation (see there) 246 – wood preservative (see there) XVIII, 48, 56, 58, 131, 132, 136, 197 – 223, 351 prior informed consent 19 – 21, 63 – Rotterdam convention 19 – 21 Priority Chemical List (PCL) 123 product, biocidal 27 – Annex (see BPD) 49, 53, 55, 57, 313, 315, 325 – 334 – biocidal products directive (see BPD) XV, 2, 21 – 23, 27, 36 – 40, 45 – 55 – consumption of biocidal products (see there) 30 – core data set for biocidal products 331 – 334, 339 – 340 – low-risk 40 – plant protection products directive, EU 22, 28, 46 – 48 – product-specific data 83 – supply chain 32 – 34 – – active-ingredient manufactures 32 – 33 – – distributors 34 – – formulators service companies 33 – 34 – types 29, 47, 51, 167, 173, 350 – 352 – – disinfectant and general XVIII, 29, 47 – – other 29
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– – pest control 29, 47 – – preservatives XVIII, 29, 47 Pseudomonas spp. 236 – P. aeruginosa 245 – 246 – P. fluorescens 246 public health (see human health) 251
q quaternary ammonium compounds (QACs) 220, 257, 259 – 261 – benzalkonium chloride 260 – centrimide 260
r radiation risk 11 reference doses (RfD) 143 – acute (ARfD) 160 registration 308 regulatory decision-making, human health 161 – 164 – active substances 161 – 162 – biocidal products 162 – 164 release estimation 171 – 174 remedial (professional) wood preservatives 213 repeated dose toxicity 148 – 149 – chronic 148 – long-term 148 – subacute 148 – subchronic 148 reporting and recordkeeping requirements 96 – registered establishments 96 reproductive toxicity, human health 150, 152 – teratogenicity 150 re-registration – fungicide 39 – pesticide 88 – 89 Re-Registration Eligibility Decision (RED) Document 88 responsible care 5 restricted / observational chemicals, Korea 117 review – first review regulation, EU 31 – program 49, 55, 317 – regulation 56 – 58 risk 141 – analysis 9 – assessment XVII, 9, 11, 14, 51, 53 – 55, 61, 89, 127, 141 – 143, 167 – 193, 354, 365 – – data requirements 169 – – definitions and process 167 – 169 – – effects assessment 184 – 187
– – exposure assessment (see there) 169 – 184 – – regulatory decision-making 188 – 193 – characterization 143, 353 – – benchmark values 143 – – human health 157 – 161 – communication 164 – cultural theory of 9 – management 2 – 3, 10 – 12 – – decisions 3 – overall integration of conclusions 365 – perceptance 3, 13 – probability risk assessment 158 – radiation risk 11 Risk Characterization Ratio (RCRs) 188 Risk Reference Doses (RfD) 143, 160 risk-benefit analysis 164 rodenticide 48, 56, 58, 131, 132, 267 – 268, 271 – 276, 321, 351 – acute compounds 271 – application method 273 – 276 – bait formulations 272 – 273 – chronic compounds 271 – Federal Fungicide, Insecticide and Rodenticide Act (FIFRA), USA XVI, 7, 20, 39, 59, 75 – 77, 167 – sub-acute compounds 271 – use pattern 273 – 276 Rotterdam Convention 6
s safety – data sheet 61, 113, 122, 125, 137, 138, 312, 321 – – material safety data sheet (MSDS) 119 – Health and Safety Guides (HSGs) 18 – Intergovernmental Forum on Chemical Safety (IFCS) 19 – International Program on Chemical Safety (IPCS) 18 – margins (MOS) 158 – 159, 161, 361 – Office of Food Additive Safety 76 Salmonella spp. 239 sanitizer 132, 134, 138 Scandinavia 70 – 71 science / scientific 15 – principle 15 scope 30 – gray areas 30 screening information data set (SIDS) 18 sediment 186, 291 – surface water and sediment 180 – 182 sensitization, human health 147
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SEPA (State Environmental Protection Agency), China 121 Seveso directive, EU 63 sewage treatment plants (STPs) 178, 180 Shigella spp. 239, 245 SIDS (screening information data set) 18 silicone – elastomers 295 – sealant 243 slime deposit 225, 229 – 231 slime-forming bacteria 227 slimicide (see also papermaking process) XVIII, 54, 132, 138, 225 – 232, 351 – active ingredients 231 – algae 229 – bacteria (see there) 226 – 227, 230 – biocidal products 231 – cooling tower 229 – fungi (see there) 227 – 228 – papermaking process (see there) 225 – 226, 232 – performance 230 – pulp 225, 227 – slime deposits 229 – 231 Slovenia 138 – 139, 140 – cosmetics (see there) 138, 139 – national chemicals bureau 139 sodium hydroxide 255, 261 – 263 soil compartment 182 – 184, 186 – 187, 363 South Africa 137 – 138 – bureau of standards 137 – hazardous substances act 137 – safety data sheet 137 South America 138 – North American Free Trade Agreement (NAFTA) 138 spa treatment (see swimming pools and spa treatment) 245 – 246 Special Review and Registration Division (SRRD) 76 spore, slimicide 228 – spore-forming bacteria 227 State Einvironmental Protection Agency (SEPA), China 121 Staphylococcus aureus 236 Staphylococcus epidermidis 236 structure-activity relationship 109, 177 substance of concern 308 Substances Control Law, Japan 104 – 112 surface – coating preservation 244 – 245 – – dry film 24 – – in-can 244 – water and sediment 180 – 182
surfactant 231 Sweden / Swedish 45, 70 – 71 – sunset program 23 swimming pools 132, 134 – and spa treatments 245 – 246 – – Acanthamoebae 245 – – adenoviruses 245 – – Cryptosporidium parvum 245 – – dermatophyte fungi 245 – – Giardia lamblia 245 – – hepatitus A virus 245 – – Mycobacterium marinum 245 – – Naegleria fowleri 245 – – papilloma virus 245 – – Pseudomonas aeruginosa 245 – – Shigella 245 Swiss Agency for the Environment, Forrests, and Landscape (BUWAL or SAFEL) 136 Switzerland 59, 135 – 137, 140 – Federal Office of Public Health (BAG) 135 – Ordinance on Environmentally Hazardous Substances (OEHS) 136 – Toxic Substances List (Giftliste) 135
t task force (TF) 41 – 42 – memorandum of understanding 42 TBT (tributyl tin) 20 tebuconazole 54 technical – guidance document on risk assessment 53 – 55, 173 – notes for guidance (TNG) 41, 49, 51, 324 teratogenicity 150 terrestrial compartment 168 test – guidelines, OECD 17 – methods 51 textile preservation 246 – Anthrenus flavipes 246 – Aspergillus niger 246 – Bacillus anthracis 246 – Bacillus subtilis 246 – Penicillium spp. 246 – Pseudomonas aeruginosa 246 – Pseudomonas fluorescens 246 – Tinea pellionella 246 – Tineola bisselliela 246 thiram 290 threshold exposure levels 157 – 158 tin 117, 130, 290 – tributyl tin oxide 292 Tinea pellionella 246
379
Tineola bisselliela 246 tolerance – exemption from tolerance, pesticide chemical residues 84 – 85 – reassessment 88 – 89, 93 toxic / toxicity – acute toxic effect 146 – 147 – repeated dose toxicity (see there) 148 – 149 – reproductive toxicity 150 Toxic Chemicals Control Law (TCCL), Korea 115 – 118 Toxic Substances Control Act (TSCA), USA 15, 128, 134 Toxic Substances and Hazardous Wastes Control Act (TSHWCA), Philippines 122 Toxic Substances and Hazardous Wastes Control Act (TSHWCA), US 122 Toxic Substances List (Giftliste), Switzerland 135 toxicokinetics and metabolism, human health 147 – 148, 154 trade 2 transnational corporations 5 tributyl tin (TBT) 20 tri-n-butylin oxide (TBT) 211, 292 twin-track approach 58
u UK (United Kingdom) 45, 67 – 69 UN Conference on the Human Environment (UNCHE) 18 UN Food and Agriculture Organization 16 UN Conference on Environment and Development (UNCED) 19 – Chapter 19 of Agenda 21 19 UN Environment Program (UNEP) 18 US (United States) 75 – 99 – North American Free Trade Agreement (NAFTA) 138 – regulatory equivalents 78 – South America (see there) 138 US Department of Agriculture 11 use and marketing directive, EU 45
w warfarin 271 water, surface water and sediment 180 – 182 wettable powders (WPs) 280 wood preservative XVIII, 48, 56, 58, 131, 132, 136, 197 – 223, 351 – application methods 208 – 210 – biological degradation (see there) 197 – 200 – disposal of treated wood 217 – 218 – durability 207 – 208 – efficacy 222 – mechanism of action 218 – 221 – – insecticides 220 – 221 – – microbiocides 218 – 220 – – some characteristics 200 – 201 – systems 215 – 216 – – amateur 216 – – industrial 211 – 213, 215 – – remedial 213, 216 – – usage rates 216 – 217 – treatability 207 – 208 – types 210 – 214 – – active substances 214 – – amateur 213 – 214 – – biological hazard classes 203 – 206 – – curative 200 – – curative preservative treatments 207 – – degree of protection 201 – 202 – – desirable characteristics 201 – – European chemicals bureau 214 – – industrial 211 – 213 – – preventive 200 – – preventive preservative treatments 206 – – regulation 200 – – remedial (professional) 213 – – service factors 203 Workplace Hazardous Materials Information System (WHMIS), Canada 135 World Health Organization (WHO) 7, 16, 240 World Trade Organization 19 – 21, 121 World Wide Fund for Nature 6
z v viruses 245, 341 – 349
zinc pyrithione 290, 293 zineb 290