Research Needs for Radiation Protection: Recommendations of the National Council on Radiation Protection and Measurements (Ncrp Report ; No. 117)

NCRP REPORT No. 117

RESEARCH NEEDS FOR RADIATION PROTECTION Recommendations of the NATIONAL COUNCIL O N RADIATION PROTECTION AND MEASUREMENTS

Issued November 30,1993

National Council on Radiation Protection and Measurements 7910 Woodmont Avenue 1 Bethesda, MD 20814

LEGAL NOTICE This Report was prepared by the National Council on Radiation Protection and Measurements (NCRP). The Council strives to provide accurate, complete and useful information in its reports. However, neither the NCRP, the members of NCRP, other persons contributing to or assisting in the preparation of this Report, nor any person acting on the behalf of any of these parties: (a) makes any warranty or representation, express or implied, with respect to the accuracy, completeness or usefulness of the information contained in this Report, or that the use of any information, method or process disclosed in this Report may not &ge on privately owned rights; or (b) assumes any liability with respect to the use of, or for damages resulting from the use of any information, method or process disclosed in this Report, under the Civil Rights Act of 1964, Section 701 et seq. m amended 42 U.S.C. Section 2000e et seq. (Title V I . or any other stdutory or common law theory goveining liability.

Iibmy of Congless Cdoging-in-PublicationData National Council on Radiation Protection and Measurements. Scientific Committee 83. Research needs for radiation protection : recommen&tions of the National Council on Radiation Protection and Measurements. c.m. -- (NCRP report ; no. 117) p. Developed by Scientific Committee 83 of the NCRP. "Issued November 30, 1993." Includes bibliographical references and index. ISBN 0-929600-32-0 1. Ionizing radiation--Safety measures. 2. Radiation dosimetry. 3. Ionizing radiation--Health aspects. I. Title. II. Series. [DNLM: 1. Radiation Protection. 2. Radiation Injuries. 3. Radiation Dosage. 4. Risk. 5. Research. WN 650 N27913r 19931 RA569.N353 1993a 616.9'89705-dc20 DNLMmLC for Library of Congress 93-34922 CIP

Copyright 0 National Council on Radiation Protection and Measurements 1993 All rights reserved. This publication is protected by copyright. No part of this publication may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotation in critical articles or reviews.

Preface This Report, developed by ScientSc Committee 83 of the NCRP, was formulated a s a result of a request by the U.S. Nuclear Regulatory Commission for the NCRP to provide advice on research needed to improve the bases for recommendations and regulations for radiation protection. I n 1988, the President of the NCRP asked the members of the Council to identify "critical questions in research, including laboratory and epidemiologic research, related to radiation protection and requiring resolution a t this time." The responses overwhelmingly identified estimation of the risks of low dose, and low-dose rate, low-LET radiation a s being the most important issue, but other problems were also singled out. It was with this background that Scienfic Committee 83 commenced its work. The Committee first created a listing of categorical needs, each backed by a statement of significance and rationale. These needs and the accompanying narrative were reviewed by a board of consultants who also critiqued the draft report before it was forwarded for the Council's review. Attempts were made to prioritize the recommended areas of research. However, no rational basis on which to do so could be defined and, therefore, no prioritization has been made or intended. Serving on Scienti6c Committee 83 during the preparation of this Report were:

S. J a m e s Adelstein, Chairman Harvard Medical School Boston, Massachusetts

Members Bruce B. Boecker Inhalation Toxicology Research Institute Albuquerque, New Mexico

Barbara J. McNeil Harvard Medical School Boston, Massachusetts

iv / PREFACE Antone L. Brooks Battelle Pacific Northwest Laboratories Richland, Washington Kenneth R. JSase Stanford Linear Accelerator Center Stanford, California

Roy E. Shore New York University Medical Center New York, New York

William L. Templeton Battelle Pacific Northwest Laboratories Richland, Washington

Amy Kronenberg Lawrence Berkeley Laboratory Berkeley, California

Consultants

Michael A. Bender Brookhaven National Laboratory Upton, New York John D. Boice, .Jr. National Cancer Institute Bethesda, Maryland Melvin W. Carter Atlanta, Georgia

William R. Hendee Medical College of Wisconsin Milwaukee, Wisconsin John B. Little Harvard School of Public Health Boston, Massachusetts Robert W. Miller National Cancer Institute Bethesda, Maryland

Merril Eisenbud Robert A. Schlenker Chapel Hill, Argonne National North Carolina Laboratory Argonne, Illinois

R J. Michael Fry Oak Ridge National Laboratory Oak Ridge, Tennessee

Paul Slovic Decision Research Eugene, Oregon

PREFACE / v

NCRP Secretariat William M. Beckner The Council wishes to express its gratitude to the participants in the work of Scientific Committee 83 for the effort they have made to produce this Report.

Charles B. Meinhold President, NCRP Bethesda, Maryland November 1, 1993

Contents Preface

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iii

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1

1. Introduction

Cellular a n d Molecular Biology . . . . . . . . . . . . . . . . 2.1 Acute Molecular Changes Produced by the . Exposure of Cells to Ionizing Radiation . . . . . . . . . 2.1.1 Risk of Mutation a s a Function of Dose Rate in Human-Derived Cell Systems . . . . . . . . . 2.1.2 Cellular and Molecular Changes Following Combined Exposures to Radiation, Drugs and Chemicals . . . . . . . . . . . . . . . . . . . . . . . 2.1.3 Molecular Markers for Cells a t Risk for Carcinogenesis in the Respiratory Tract . . . 2.2 Genetic Variability and Risk of Radiation-Induced Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Biochemical and Genetic Responses . . . . . . . . . . . 2.3.1 Induction of DNA Repair Enzymes (and Other Proteins) . . . . . . . . . . . . . . . . . . . . . . 2.3.2 Expression of Genes Associated with Mutational Loss, Activation and Induction . 2.3.3 Radiation-Induced Genetic Alterations a s a Function of Time for Cells That Retain Proliferative Capacity . . . . . . . . . . . . . . . . . 2.3.4 Persistence of Radiation-Induced Genetic Alterations . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.6 Biologic Bases for Species Differences in Radiation Response . . . . . . . . . . . . . . . . . . . 2.3.6 Studies in Animal Systems to Test Biologically Based Models of Carcinogenesis and Intervention in Radiation Carcinogenesis . . . . . . . . . . . . . . . . . . . . . . . 2.4 In-VitroStudies . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Biologic Markers of Radiation Exposure . . . . . . . .

viii / CONTENTS 2.6 Estimates of Genetic Effects . . . . . . . . . . . . . . . . . 2.6.1 Genetic Alterations in Germ Cells . . . . . . . . 2.6.2 Heritable Genetic Risk a s a Function of Dose Rate and Ionization Density ........ 2.6.3 Heritable Genetic Risks in Females of Species other than the Mouse . . . . . . . . . . . 2.6.4 Radiation-Induced Genetic Alterations in Reproductive Tissues . . . . . . . . . . . . . . . . . . 2.6.5 Induction of Aneuploidy . . . . . . . . . . . . . . . . 2.6.6 Multifactorial Genetic Diseases . . . . . . . . . . 2.7 In-UteroExposure . . . . . . . . . . . . . . . . . . . . . . . . . 2.7.1 Cancer and Developmental Risks ........ 2.7.2 Mental Retardation Risks . . . . . . . . . . . . . .

12 12 13 13 14 14 14 15 15 16

Dose Determination: Models, Measurements, Markers a n d Exposure Analysis . . . . . . . . . . . . . . . 17 3.1 Biologic and Physiologic Models .............. 18 3.1.1 Modscation of Current Metabolic Models for Internally Deposited Radionuclides Taking into Account Variations in Age, Health Status and Anatomy . . . . . . . . . . . . 18 3.1.2 Relationship of Bioassay Results (Excretory Measurements) to the Variables in Biokinetic Models . . . . . . . . . . . . . . . . . . . . 19 3.1.3 Determination of the Impact of Nonuniform Deposition and Retention of Radionuclides and Nonuniform External Exposure on Effective Dose and Consequent Risk . . . . . . 20 3.2 Physical Dosimetry Models and Radiation Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21 3.2.1 Development of Improved Calculational Models for Determining the Distribution of Energy Deposition &om Internal Emitters . 21 3.2.2 Development of Improved Calculational Models for Relating Exposure to External Radiation Fields ...................... 22 3.2.3 Relationship of the Microscopic and Submicroscopic Distribution of Energy Absorbed to the Risk of Radiation Injury . . . 23

CONTENTS / ix 3.2.4 Improvement of the Data Base of

Environmental Parameters for Use i n Dose Assessment Models . . . . . . . . . . . . . . . . . . . 23 3.3 Experimental Techniques, Measurements and Instrumentation . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.3.1 Development of Dosimetric Techniques for the Experimental Verification of Complex Calculational Models . . . . . . . . . . . . . . . . . . 25 3.3.2 Development of Accurate and Sensitive Methods for Monitoring Intake . . . . . . . . . . 25 3.3.3 Development of a More Exact Method for Monitoring Uranium Uptake . . . . . . . . . . . . 26 3.3.4 Development of a Generic Guidance Document for Environmental Monitoring of Radionuclides and Chemicals ........... 26 3.3.5 Development of Instrumentation to Relate Radiation Field Quantities to Relevant Dose Quantities . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.4 Exposures to Specific Sources . . . . . . . . . . . . . . . . 27 3.4.1 Development of Accurate Models of the Dose to Bronchial Tissues &om Radon Progeny in Relation to Airborne Radon Concentration . 27 3.4.2 Development of Screening Models for Environmental Contaminants . . . . . . . . . . . 28

. . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

4. Risk Assessment 4.1 Animal Studies and their Relationship to Human

Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4.1.1 Species Dose-Response Differences a t the Tissue, Cellular and Molecular Levels . . . . . 30 4.1.2 Integration of Animal and Human Data to Provide the Best Estimates of DoseResponse, Relative Biological Effectiveness and Dose-Rate Effectiveness Factor . . . . . . . 30 4.1.3 Studies in Animal Systems to Validate Mathematical Models of Radiation-Related Carcinogenesis ....................... 3 1 4.1.4 Determination of the Influence of Parental Exposure on Leukemia Risk in Offspring . 31 4.2 Human Epidemiologic Studies of Low-LET Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

.

x / CONTENTS 4.2.1 Improvement of Estimates of the Risks from

4.3

4.4 4.6

4.6

Exposure to Low-Dose and Fractionated or Protracted Low-LET Irradiation . . . . . . . . . 33 4.2.2 Development of Additional Information on the Temporal Expression of RadiationInduced Cancer . . . . . . . . . . . . . . . . . . . . . . 33 4.2.3 Development of Better Methods for Transfer of Risk Estimates Across Populations ..... 34 4.2.4 Development of a National Dose Registry of Radiation Workers . . . . . . . . . . . . . . . . . . . . 35 Risk Assessment of Exposure to Internal Radionuclides and Heavy, Energetic High-LET Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 4.3.1 Life-Span Studies of Dose-Response Relationships for Internally Deposited Radionuclides in Laboratory Animals . . . . . 35 4.3.2 Studies of Human Populations Exposed to Internally Deposited Radionuclides Medically Administered . . . . . . . . . . . . . . . . 36 4.3.3 Improvement of the Estimates of Risk &om Radon Exposure . . . . . . . . . . . . . . . . . . . . . 36 4.3.4 Improvement of Estimates of Risk for l3'1 . . 38 4.3.5 Determination of the Biologic Effects of Radiation in Space . . . . . . . . . . . . . . . . . . . 39 4.3.6 Determination of the Relative Biological Effectiveness of Neutrons in Humans . . . . . 39 Improvement of Epidemiologic Methods and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40 Elaboration of Risks by Studying Host Susceptibility Factors . . . . . . . . . . . . . . . . . . . . . . 41 4.5.1 Development of Models that Provide Individualized Molecular Risk Assessment for Cell Survival and Carcinogenesis . . . . . . 42 4.6.2 Characterization of Radiation Risks in Relation to Host Susceptibility Factors and Age a t Exposure ..................... 42 Interactions of Radiation and Other Toxicants . . . 43

6. Prevention, Intervention a n d Perception . . . . . . . . 45 6.1 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

CONTENTS / xi

5.1.1 Utilization of Molecular and Cellular

Techniques to Identlfy Individuals Who May Have an Increased Risk for RadiationInduced Cancer . . . . . . . . . . . . . . . . . . . . . . 45 6.1.2 Relationship of Patient Dose to Radiologic Image Quality and Diagnostic Outcomes . . . 45 5.1.3 Assessment of the Impact of New Technologies and Changing Demographics on Risks from Medical Radiation Sources . 46 6.1.4 Acquisition of Additional Data on Transmission, Scattering and Fragmentation That Will Help in the Development of Better Shielding . . . . . . . . . 47 5.2 Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 5.2.1 Development of Information on Countermeasures Following Large Radiologic Accidents . . . . . . . . . . . . . . . . . . 48 5.2.2 Development of Informational Materials for Public Use after a Radiation Accident . . . . . 49 5.3 Perception and Public Policy . . . . . . . . . . . . . . . . . 49 5.3.1 Development of Common Expressions of Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.3.2 Development of a Better Understanding of the Public's Perception of Risk and Improved Methods of Presenting Information on Exposure and Risk . . . . . . . 50 5.3.3 Assessment of Societal Values with Respect to Radiation and Other Risks . . . . . . . . . . . 51 5.3.4 Development of a Level of Acceptability for Different Types of Risk . . . . . . . . . . . . . . . . 52

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6. Resource Requirements

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55

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71

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82

References

NCRP Publications Index

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1. Introduction This Report addresses research needs for establishing guidelines for radiation protection from ionizing radiation and in some instances the combination of ionizing radiation and other agents. Research needs in the area of nonionizing radiation are not addressed. The general fields of research for which increased information would be most useful can be organized into the following categories: biologic studies including host factors and modifiers dose determination including models and exposure analysis risk assessment prevention and intervention including public understanding and public policy I n addition, there are five central, and a number of subsidiary, questions facing the radiation protection research community. *

-

What are the overall risks associated with low-dose exposure (below 100 mSv). Particularly, what is the shape of the lowdose-response curve in humans for cancer induction, inheritable disorders and developmental abnormalities? What are the effects of dose rate, if any, at-doses below 100 mSv and a t what dose levels does a linear response become "biophysically" sensible and not just a n assumption? What are the effects of ionization density, age a t exposure and individual susceptibility? How can we better define the spatial and temporal distribution of dose to improve the accuracy and precision of the dose term for dose-response relationships a t both macroscopic and microscopic levels? To what extent do new advances in molecular genetics and structural biochemistry permit us to expand our basic knowledge of the effects of radiation, thereby, shedding light on the steps leading to the production of cancer and other damage? From this knowledge can we derive a n insight into

2

/

1. INTRODUCTION

dose-response relationships a t a level not attainable by animal or human epidemiologic studies? Given that we live i n a world that has radiation in the environment, the work place, the clinic and outer space, what preventive measures can be taken to reduce exposure, or the potential for exposure and, when exposure has taken place, what intervening measures can be taken to minimize harm? What should we do about radiation combined with chemicals and other potential environmental toxins? Given the complexity of radiation effects, what can we do to promote public understanding and to ensure rational and informed judgements on policies related to the practice of radiation protection? There is no notion that the list of recommendations in this Report is complete or even definitive, but each of the 60-odd recommendations is considered important. Like all research agendas it is subject to revision a s data accrue and a s new developments bring further issues to the forefront. It is recommended that the question of research needs for radiation protection be revisited every three to five years.

2. Cellular and Molecular Biology Research that illuminates molecular effects of acute radiation exposure and of chronic low-dose-rate exposure of humans may suggest methods of intervention following such exposures. New molecular and biochemical approaches are likely to enhance our understanding of cellular and tissue responses to ionizing radiation by contributing increased knowledge of radiation effects. Such approaches could provide a biologic basis for observed variations in the risks of carcinogenesis and in certain deterministic effects among individuals following radiation exposure. Efforts are needed to reduce uncertainties in the assessment of risks for defined biologic endpoints following exposure. Particular attention should be paid to the risks of low-dose, lowdose-rate exposures, high-LET exposures and combined exposure to radiation and other environmental agents. Advances in molecular biology and biochemistry have presented unprecedented opportunities to increase our understanding of cellular, tissue and organ responses to low doses of ionizing radiations. Certain techniques, such as the polymerase chain reaction (Saiki et al., 1988) and in-situ hybridization (Pinkel et al., 1986), permit the analysis of subtle alterations in the genetic constitution and functional integrity of individual cells within a complex milieu. Using these new approaches, it is possible that subtle effects of low-dose and lowdose-rate exposure will be revealed.

2.1 Acute Molecular Changes Produced by the Exposure of Cells to Ionizing Radiation

Studies are needed to improve the methods for the quantitation and distribution of DNA strand breaks, chromatin

4 / 2. CELLULAR AND MOLECULAR BIOLOGY

breaks and base alterations a t low doses. Biophysical models predict that the distribution of energy differs for sparsely and densely ionizing radiations and that these differences may be crucial to the increased effectiveness of densely ionizing radiations for a variety of biologic endpoints. These models require rigorous testing for the particular cases of low-dose and low-dose-rate exposures.

2.1.1

Risk of Mutation as a Function of Dose Rate in Human-Derived Cell Systems

The magnitude of the effect of dose rate on the induction of mutations in somatic cells and on the induction of cancer remains an open question that needs to be addressed. In addition, the biologic basis for the reported increased effectiveness of exposure to low-dose-rate, densely ionizing radiation for the induction of neoplastic transformation in vitro, tumorigenesis a t selected sites in vivo and somatic mutation has not been adequately assessed. Studies should be designed to determine whether these observations may be verified in various cell and tissue types of human or primate origin.

2.1.2

Cellular and Molecular Changes Following Combined Exposures to Radiation, Drugs and Chemicals

Humans are exposed in the environment to mixtures of chemicals, drugs and radiation. Our understanding of the risks of combined exposure to radiation and other environmental agents is poor and suggests an area for investigation. It is important to determine whether the biologic responses from these combined exposures can be predicted. Radiation protection standards, in general, have been set for exposure to radiation alone and do not take into account potential interactions between damage induced by radiation and that produced by additional agents. It is not possible to conduct epidemiologic studies that will address all potential interactions among the wide variety of agents a s a function of exposure sequences and

2.2 GENETIC VARIABILITY AND RISK

/ 5

dose patterns. However, short-term cellular and molecular techniques can provide evaluation over a wide range of conditions of exposure. With such approaches, mechanisms of interaction can be defined and then verified with animal experiments. This level of understanding can help in extrapolation &om individual chemicals or types of radiation to combined exposures.

2.1.3

Molecular Markers for Cells at Risk for Carcinogehesis in the Respiratory Tract

The only radionuclide exposure for which lung cancers have been observed in humans is exposure to radon and its progeny in uranium liiiners. However, radiation protection practice requires recommendations and standards covering a broad range of inhaled radionuclides that emit alpha and beta particles or photons with dose-response relationships different &om those occurring after exposure to radon and its progeny. A crucial step in the r e h e m e n t of risk estimates for cancer of the respiratory tract is the precise identikation of the number and type($) of cells a t risk for carcinogenesis. Information on the number and distribution of these cells in suitable animal models, together with determinations of Relative Biological Effectiveness (RBE), dose and dose-rate response for various radionuclide exposures is essential in order to permit appropriate extrapolations &om radon-associated human lungcancer data to the risks of exposures of other inhaled radionuclides.

2.2 Genetic Variability and Risk of

Radiation-Induced Cancer It is assumed that there is a wide range of susceptibility in human populations to radiation insult in the range of exposures of interest to radiation protection. It is important to determine whether there is a n overall genetic basis for such variability in cancer risks among individuals. Standards that take into

6 / 2. CELLULAR AND MOLECULAR BIOLOGY

account a range of susceptibilities may need to be considered in order to limit radiation exposures of sensitive subpopulations. The ability to identify host factors that are indicative of radiation sensitivity (or resistance) is important both for radiation protection and for an understanding of the radiationdependent pathways in carcinogenesis. Certain individuals have genetic disorders that are associated with deficiencies in DNA repair. In most cases, these individuals have an increased "spontaneous" incidence of cancers. Little is known about cancer induction by radiation among individuals with these disorders (e.g., ataxia telangiectasia, Bloom's syndrome, Fanconi's anemia, xeroderma pigmentosum and Cockayne's syndrome). Even less is known about the possibility of an increased risk of radiogenic cancer in individuals who are heterozygous carriers of these and other recessive inherited disorders (e.g., constitutional heterozygosity for one of several tumor suppressor genes). The number of persons in this latter grouping are far more numerous than those with overt disease. Emphasis should be placed on the identification of additional genetic traits that are indicators of increased susceptibility to cancer. As these genes are identified, it will be important to determine whether low-dose radiation exposure increases the likelihood that alterations associated with initiation or progression of carcinogenesis will occur in these loci. An attempt should be made to clarify these issues using in-vitro methods and tissue explants.

2.3 Biochemical a n d Genetic Responses

It is important to illuminate the biochemical steps of initial and delayed cellular and tissue responses to radiation with a view toward the design of avenues for interventions aimed a t limiting cancer induction and developmental defects. An understanding of biochemical and molecular pathways involved in cellular responses to ionizing radiation will assist in the development of strategies to counteract the effects of these exposures. It is likely that the constellation of cellular responses to low-dose, low-dose-rate exposure and those following acute exposure are somewhat different. While emphasis should be

2.3 BIOCHEMICAL AND GENETIC RESPONSES /

7

placed on the responses to very low-dose exposures, with a view toward intervening in the process of radiation-induced carcinogenesis, some attention should also be given to responses to higher doses such as might occur in accidents. These investigations may provide additional insight into the design of therapeutic strategies,

2.3.1

Induction of DNA Repair Enzymes (and Other Proteins)

Little information is available on the particular proteins involved in the acute radiation response and their functions. In addition, little is known about the involvement of specific proteins in programed cell death. Identillcation of the proteins implicated in such responses might lead to the development of therapeutic strategies to limit radiation necrosis following acute exposures. Studies are also required to identi? the DNA repair enzymes involved in the cellular response to ionizing- radiation exposure. Mutant cell lines with known DNA repair deficiencies, coupled with their repair-competent parental lines, should aid in the identification of specific enzymes involved in repair of radiation damage. Low doses of low-LET radiation have been shown to decrease the responsiveness of blood lymphocytes and some fibroblasts to acute high doses of radiation (Wolff et al., 1988). These low doses cause the release of unique proteins. It has been postulated that these proteins may be involved in the repair of DNA damage. I t is important to determine whether the induced proteins are repair enzymes and whether they can be induced in epithelial cells since these cells are so critical in carcinogenesis. These studies need then to be expanded into animals. If there is a change in the risk of cancer per unit dose over a range of doses, then such doses will not produce cancer as a linear function of dose. Therefore, the use of linear extrapolation models on data at high doses to define radiation dose-response relationships a t low doses may only be approximately applicable.

8 / 2. CELLULAR AND MOLECULAR BIOLOGY 2.3.2

Expression of Genes Associated with Mutational Loss, Activation and Induction

Extensive characterization of molecular genetic alterations commonly associated with the development of particular neoplasms is underway for a variety of human tumors. Studies are needed to describe the risk of radiation-induced alteration of genetic markers which have already been associated with the development of human cancers. Such studies should use human biopsy materials where possible and define the role of LET, dose and dose rate on mutational loss, activation and expression of genes associated with cancer induction. Certain in-vitro and invivo model systems, e.g., mouse mammary gland and rat tracheal epithelial cells may provide useful information on the modulation of cellular responses by host factors.

2.3.3

Radiation-Induced Genetic Alterations as a Function of Time for Cells That Retain Proliferative Capacity

The time course for the development of permanent genetic alterations in somatic cells following radiation exposure is a subject for investigation. Research has suggested that there are several phases to the development of heritable changes a t the DNA level - a rapid component that is a function of the ionization of the DNA and its aqueous environment, a second phase comprised of damage produced or resolved i n the first cell division cycle, and a more protracted phase of lesion modScation or development which may result in cell death, mutation or genomic instability. Further studies are required to define the importance and mechanisms of the delayed expression of radiation damage.

2.3.4

Persistence of Miation-Induced Genetic Alterations

The persistence of radiation-induced genetic alterations invivo has not been widely examined. Experimental approaches should be developed to determine whether there may be

2.3 BIOCHEMICAL AND GENETIC RESPONSES /

9

selection for or against the various types of alterations produced. Model systems for such studies might include peripheral blood lymphocytes, epithelial cells and germ cells.

2.3.6 Biologic Bases for Species Differences in Radiation Response To maximize the use of dose-response data obtained in nonhuman biologic systems for radiation protection applications, additional research should be devoted to establishing stronger links among studies conducted in different species of animals, and among studies a t the tissue, cellular and molecular levels. One recent example of an area in which information on species variation in response may have some bearing on the differences in rates of cancer induction is that of preferential repair of actively transcribed DNA, wherein the ability to repair nontranscribed DNA has been shown to vary widely between human and rodent cells exposed to certain environmental agents 1986; Mellon et al., 1986). I t (J3ohr et al., 1985; Madhani et d., is necessary to understand and account for differences in doseresponse relationships for a variety of radiation-induced endpoints in order to minimize errors in extrapolation of risk among species.

2.3.6

Studies in Animal Systems to Test Biologically Based Models of Carcinogenesis and Intervent ion in Rudiation Carcinogenesis

A limited number of animal studies may be required to evaluate specific biologic parameters in a multistage model of radiation-induced carcinogenesis.Emphasis should be placed on studies that cannot be carried out in vitro, such as the role of tissue organization on progression of initiated cells. Additional studies designed to focus on strategies for intervention in the process of carcinogenesis in animals that have been exposed to radiation may be useful, if the biologic parameters in a

10 / 2. CELLULAR AND MOLIECULAR BIOLOGY multistage model of radiation-induced carcinogenesis can be defined.

2.4 In-Vitm Studies

It is important to develop new resources for the in-uitro study of the processes leading to radiation-induced cancer in humans. These should include methods for detection of genetic alterations in transformed cells, methods for determination of candidate markers and perfection of biologic dosimeters. New techniques such as the polymerase chain reaction, fluorescence in-situ hybridization and the use of transgenic animals may enhance the likelihood of detecting important genetic alterations. Emphasis should be placed on the use of human biopsy materials in concert with these or other novel approaches. To date, the study of radiation effects a t the cellular and subcellular levels has been limited to a narrow group of model systems, many of which have a n unknown relevance to the assessment of the risks of radiation-related carcinogenesis. Emphasis should be placed on studies using human epithelial cells. In addition to carcinogenic risk, the effect of radiation exposure on the functional integrity of nondividing cells such as neurons is important to consider. Damage can accumulate as a knction of age and, in the case of astronauts, damage would be expected to possibly increase more rapidly on extended space missions due to potentially higher doses of high-LET radiations. Few measurements have been made on the cellular and molecular changes that are present during the early stages of carcinogenesis other than possibly the development of skin cancer in hairless mice. Many useful molecular probes have been developed for human cells and tissues to define changes as cells move from normal to neoplastic. These alterations in gene expression, activation of genes and gene loss provide mechanistic probes to help define the carcinogenic process. The expression of specsc mRNAs and proteins which may have important functions in the cellular response to radiation should be examined, e.g., growth factors and growth factor receptors,

2.5 BIOLOGIC hrlARKERS OF RADIATION EXPOSURE I

11

and cell-surface antigens. Cellular changes also need to be defined such a s alterations in cell proliferation, chromosome translocations and other karyotypic alterations. If these probes can be applied in animal models, such a s dogs or subhuman primates, where individual animals and tissues can be followed over time during the carcinogenic process, additional understanding can be developed. The process can be followed from the initial insult delivered by well-defined radiation doses, through the early changes in the cells and on to the ultimate development of cancer. Combining molecular techniques with animal models will link the molecular, cellular and animal data derived both in vitro and in vivo to human risks and will help define mechanisms involved in carcinogenesis. Better understanding of the biologic processes will help to validate mathematical models of carcinogenesis, which can, in turn, lead to new experimental directions.

2.5 Biologic Markers of Radiation Exposure Chromosome aberrations in human blood lymphocytes have provided a good biologic dosimeter for acute, whole-body radiation exposure when the cells are sampled shortly after the exposure mender et al., 1989). However, there are limitations to the usefulness of this system. First, a t low total doses it is very expensive to sample and score an adequate population of cells to estimate dose. Second, the distribution and number of aberrations change following partial body exposure or when there is a long time between exposure and evaluation of the aberration frequency. Both of these problems limit the utility of chromosome aberrations a s a biologic dosimeter. New techniques of either staining repeated sequences a t the telomere or centromere region or chromosome painting which uses molecular probes to paint a whole chromosome make it possible to score chromosome translocations more rapidly and accurately. Certain of these aberrations are stable and not markedly influenced by time after exposure. Their potential a s dosimeters should be explored further. Additional techniques to estimate exposure and dose are being developed by measuring the induction of mutations in

12 / 2. CELLULAR AND MOLECULAR BIOLOGY

blood lymphocytes a t the HPRT and HLA gene loci and in red blood cells at the glycophorin A and beta globin gene loci. If properly validated, these procedures may be usefulin screening large human populations accidentally exposed to radiation.

2.6 Estimates of Genetic Effects A new analysis of Japanese atomic-bomb data suggests a mutation doubling dose of about 2 Sv for acute exposure, a value which is higher than past estimates (Nee1 et al., 1990). Additional data are needed to confirm or disprove this. There are several views on how to proceed in developing sensitive and appropriate indices of mutation rates. One view is that new developments are needed with respect to protein markers: new technical means of looking for small radiationinduced changes in large numbers of proteins and better means for detecting "null" mutations in such proteins. Another is that genetic effects are best tested at the DNA level. There is general agreement that the greatest opportunity for such studies is in Hiroshima and Nagasaki. Work is underway there to establish cell Lines for DNA studies based upon exposed and unexposed parents and their offspring. The problem associated with further DNA studies is the rarity and heterogeneity of the radiationinduced DNA alterations. Additional DNA methods are required to deal with these problems before there will be a reasonable hope of learning much more from the established cell lines.

2.6.1 Genetic Alterations in Germ Cells I t is important to define genetic alterations more accurately in germ cells. New techniques to detect changes in sperm of humans and other animals are being developed using in-situ DNA hybridization. Additional mutation tests in transgenic animals have been reported. These new methods will facilitate an understanding of the impact of multifactorial genetic diseases on morbidity, mortality and radiation risk and, thereby, improve overall risk assessment.

2.6 ESTIMATES OF GENETIC EFFECTS /

2.6.2

13

Heritable Genetic Risk as a Function of Dose Rate and Ionization Density

The influence of dose rate on the induction of transmitted mutations in germ cells, especially for high-LET radiation, remains an open question. Studies of internally deposited plutonium demonstrated that the RBE for transmitted mutations is low (Russell et al., 1978). However, evidence indicates that the severity of the genetic damage produced by alpha particles may be qualitatively more serious than that induced by gamma rays (NCRP, 1989). Because of the sensitivity of mouse oocytes to cell killing (Dobson and Cooper, 1974) assumptions based on mouse data concerning risks to offspring of persons irradiated with densely ionizing radiations a t low-dose rates over long periods of time have been called into question (Dobson et al., 1978). Also, the data for neutroninduced mutations have been obtained with doses unlikely to be suitable for determining RBE values for low doses and dose rates.

2.6.3

Heritable Genetic Risks in Females of Species other than the Mouse

Data fiom the female mouse have been shown to have limited application for prediction of genetic damage in human females. Because of their synchronization, mouse oocytes are uniquely sensitive to radiation-induced cell killing (Dobson and Cooper, 1974) and, therefore, do not reflect the spectrum of mutation that would be generated in human oocytes. Thus the dose-rate effect observed in the mouse may not be applicable to other animals, especially humans. There is need for additional female animal systems to study dose-response relationships for induction of both dominant and recessive mutations. The observed unique sensitivity of oocytes to cell killing in experimental animals should be further characterized to determine whether such effects are present in exposed human oocytes.

14 / 2. CELLULAR AND M O L E C m BIOLOGY 2.6.4

Radiat ion-Induced Genetic Alterations in Reproductive Tissues

Little is known about the persistence of radiation-induced genetic alterations in germinal tissues in vivo. Experimental approaches should be developed to determine whether there may be selection for or against the various types of alterations produced and whether these have greater or less impact depending on the type of alteration. 2.6.5

Induction of Aneuploidy

Errors in chromosome segregation, resulting in aneuploidy, produce genetic diseases many of which are related to mental retardation and congenital malformations. Evidence to date that a relationship exists between radiation exposure and the induction of aneuploidy has been marginal, resulting in high doubling doses and low-risk estimates for radiation-induced aneuploidy (NAS/NRC, 1990). Recent estimates of the magnitude of genetic disease from radiation-induced aneuploidy have been made (Abrahamson et al., 1990) based on new mouse data (Griffin and Tease, 1988) and human data (Martin et al., 1986). The data base for these estimates is weak and additional information and analysis are required for these estimates to be made with the needed degree of accuracy. 2.6.6

Multifactoriul Genetic Diseases

Estimates of the magnitude of risk for multifactorial genetic diseases in the population have increased markedly during the past few years (NAS/NRC, 1990). Depending on the assumptions made for dose-response relationships for induction of these diseases and the amount of time required after exposure for the diseases to reach genetic equilibrium, multifactorial diseases can have a major impact on genetic risk estimates. The Committee on the Biological Effects of Ionizing Radiations (BEIR V) (NASNRC, 1990) suggested that "while the risks could be negligible, they could also be a s large or larger than all other" genetic risks of radiation combined. New experimental methods

2.7

IN-UTEROEXPOSURE / 15

are required to determine potential dose-response relationships for radiation-induced multifactorial genetic diseases. Some suggestions have been made for animal model systems that use direct methods (Selby, 1990) to estimate risks for genetic disorders of complex etiology (Russell, 1990). Research is also necessary to develop animal models that will define the time required after radiation exposure for multifactorial diseases to reach genetic equilibrium. Such research is difficult because of the length of time for the expression of many of these diseases, but essential because of the large potential impact multifactorial diseases could have on genetic risk.

2.7 In-Utero Exposure

2.7.1

Cancer and Developmental Risks

The influence of irradiation in utero needs to be further defined in terms of potential risk both for induction of cancer in the offspring and for developmental changes. After high-dose and high-dose-rate exposures, there were no increases in the cancer rate in the F, population of atomic-bomb survivors. However, increasing numbers of reports are being released to indicate that irradiation in utero (prenatally) at low doses and dose rates can cause increased risks for cancer induction in experimental animals (Antal et al., 1991;Benjamin et al., 1991; Watanabe et al., 1991). These studies have been conducted on a range of species with a series of different cancer endpoints. Additional research is needed to determine whether these observations are applicable to humans and whether the results can be translated into meaningful changes in human risk. Such information can be derived with additional mechanistic studies that combine in-vivo exposure of animals with in-vitro studies a t the cellular and molecular levels. This approach makes it possible to follow changes with time and radiation dose and type. When this information becomes available, extrapolation of risk between species will be improved.

16 / 2. CELLULAR AND MOLECULAZt BIOLOGY 2.7.2

Mental Retardation Risks

Mental retardation was induced in human populations exposed in utero to the atomic bombs (Schull et al., 1988). This risk has its highest sensitivity during the 8th to 15th week of gestation when approximately 30 IQ points are lost per sievert of exposure. This risk is somewhat less during the 16th to the 25th week of gestation and is thought to be low or essentially zero in other periods of gestation. This is one of the most sensitive endpoints for high-dose and high-dose-rate radiationinduced damage in utero. This observation can be further evaluated in experimental animal models to define the site and extent of the damage. Careful study of the toxic effects of radiation and other teratogenic agents is needed to unravel the neurobiology of these phenomena. The incorporation of molecular biology and neurotoxicologic concepts, approaches and techniques into studies of brain development provides opportunities for understanding the processes and defining the mechanisms involved in these effects. With this understanding, decisions concerning the shape of dose-response relationships can be made. The mechanisms of action of these effects can be addressed in animal studies i n many cases.

3. Dose Determination: Models, Measurements, Markers and Exposure Analysis To understand and to quantify the risks related to radiation exposure, and then to establish appropriate control measures, the radiation dose must be determined. For epidemiologic studies, an unbiased estimate of organ doses is needed. For radiation protection purposes, a dosimeter reading is often used, which in cases of external exposure generally errs in the direction of an overestimation of organ doses. While this may be appropriate for radiation protection, it may not be directly useful for studies in radiation epidemiology. Methods of translating between organ doses, like those calculated for the Japanese survivors and dosimeter doses for radiation protection and vice versa are needed as well as estimates of the nature and magnitude of the uncertainties and biases involved. A .example of an uncertainty assessment and analysis of bias dealing with dosimetry is that contained in the 1989 National Research Council report on Film Badge Dosimetry in Atmospheric Nuclear Tests (NAS/NRC, 1989). At the present time, calculational models do not take into consideration physiologic differences among individuals and are only beginning to adjust for differences related to age and sex. Further research and development are required to account more precisely for human metabolism and physical dose distributions related to radioactive materials taken internally. Such information is particularly needed for the determination of doses to the embryolfetus due to internal radionuclide deposition in the mother. Radiation transport calculations for dose reconstruction of both internal and external radiation sources use analytical models as well as Monte Carlo simulations. These methods

18 / 3. DOSE DETERMINATION

appear to work well a t energies above a few tens of kilovolts. However, increased sophistication is needed in modeling particle tracks on the scale of macromolecules and a t very low energies. Verification of these calculational models necessitates development of experimental techniques and instrumentation. New dosimeters, especially a biologic system using specific markers that can identify the occurrence of a radiation exposure a s well as measure its magnitude, would be a s i d c a n t advance in dosimetry (see Section 2.5). Some specific markers associated with genetic mutations have been identified. These have potential for establishing radiation exposure, if not a s quantitative dosimeters (Mendelsohn, 1990). Exposure to particular sources of radiation demands special attention in dose determination. At this time, exposure of the public to naturally occurring decay products of radon gas, potential exposure of the public to radioactive material present in the environment near contaminated disposal sites, and potential exposure of spacecraft crew members to high atomic number, high energy (HZE) cosmic radiation are three important areas in need of research.

3.1 Biologic and Physiologic Models

3.1.1

Modification of Current Metabolic Models for Internally Deposited Radionuclides Taking into Account Variations in Age, Health Status and Anatomy

Radiation protection for internally deposited radionuclides requires an in-depth understanding of the relationship between exposure by various routes (e.g., inhalation, ingestion and uptake through wounds), dose to critical tissues and cells, and the resulting biologic effects. Both the exposure-to-dose and the dose-to-response relationships are influenced by a broad range of biologic and physiologic factors. Particularly in need of being addressed is the development of metabolic models that account for age and health-related variations.

3.1 BIOLOGIC AND PHYSIOLOGIC MODELS

1 19

As more attention is given to past and present general population exposures to radionuclides in the environment, there is a n increasing need for metabolic models that reflect more accurately the differences that may occur among individuals. For instance, very young children may have patterns of radionuclide intake and uptake considerably different from adults. Individuals with diseases of the lungs, gastrointestinal tract and kidneys may exhibit rates of absorption and excretion different from individuals who are not diseased. These factors should be incorporated into the models used to calculate population doses to ensure adequate radiation protection for these subpopulations. The biologic and physiologic data describing the uptake, transfer and elimination of radionuclides and specific chemical compounds containing radionuclides need to be established. This is particularly important for medical diagnostic applications where patients may be of various ages and disease states (NCRP,1985a; 1985b).

3.1.2

Relationship of Bioassay Results (Excretory Measurements) to the Variables in Biokinetic Models

There is a need to relate accurately biokinetic models and bioassay information in order to assess potential exposure and to control intake for workers. The uncertainties associated with assessment of intake, deposition and excretion need to be better defined. Bioassay protocols are vital components of radiation protection programs for situations where internal exposure to radionuclides is possible. Results from bioassay determinations are used to detect the occurrence of exposures and to estimate the doses that will be received by various body organs and tissues. Many of the mathematical models currently available for estimating intake, deposition, excretion and subsequent organ doses from bioassay results are simplified, general purpose models, devised primarily for health protection planning. More research should be devoted to element-spec&c bioassay models and the physical, chemical and biologic factors that influence them.

20 / 3. DOSE DETERMINATION 3.1.3

Determination of the Impact of Nonuniform Deposition and Retention of Radionuclides and Nonuniform External Exposure on Effectiue Dose and Consequent Risk

Radionuclides may be deposited nonunifomly in various regions of target organs. There is a need to understand the relationship between the nonuniform deposition of radioactivity and the resultant nonuniform dose distribution to critical cells and cellular components and the ultimate risk. With penetrating low-LET radiation, the dose quantity can be averaged over an organ or organ system, whereas with low-energy electrons and alpha particles, the microscopic distribution of the energy absorption may be more appropriate for assessing the risk. It is well known that such nonuniformity of radionuclide deposition occurs in various organs from occupational, medical and environmental exposures. Each of these exposures has its own characteristics related to the energy deposited in critical cells and structures (Hui et al., 1992). Research is needed to determine when average dose calculations provide adequate information and protection and when more detailed dosimetric relationships or calculations are necessary to ensure that the required level of radiation protection is achieved. The current concept of effective dose is based on a summation of weighted risk to various body organs from acute external irradiation. The applicability of these risks to the estimation of the risks due to irradiation from internally deposited radionuclides, which may have widely differing temporal and spatial dose distributions, must be verified. Uncertainties in the specification of the appropriate dose quantity and its relationship to measured quantities and ultimate risk to the individual need to be evaluated. There is a need to define more accurately the dose quantity that is most appropriate to the assessment of the risk to an individual from internal radiation exposure, and its dependence upon age, sex and the rate at which the dose is accumulated. Effective dose, which measures the dose to the total body based on weighting partial body exposures in a prescribed way, has been recommended a s the appropriate dose quantity (NCRP, 1993).There is some question of whether specific organ or tissue

3.2 PHYSICAL DOSIMETRY MODELS /

21

doses are not more appropriate for highly nonuniform or partial body exposure, as well as exposure to low-energy electrons and other charged particles, than the effective dose. The tissue weighting factors for various organs currently applied i n the calculation of effective dose are derived from brief, acute exposures of the Japanese population to a n external radiation source, primarily of gamma rays. However, they are used to weight the risk of individual organs when exposed to low-dose and low-dose-rate chronic irradiation by x rays, gamma rays, neutrons, HZE and other charged particles. Such a procedure does not address the possible variations in the weighting factors due to these different types of exposure. Additional biologic response data are needed to define the uncertainties i n these relationships.

3.2 Physical Dosimetry Models a n d Radiation Transport

3.2.1

Development of Improved Calculatwnal Models for Determining the Distribution of Energy Deposition from Internal Emitters

The present models used for determining doses to organs from internally deposited radionuclides do not take into account the variation among individuals in age, sex and anatomy, the complex geometry of internal structures and the heterogeneity of tissues. Because of this, the uncertainty in the dose calculated from these models for any spec& individual is large. This is caused, in part, by the lack of biologic and physiologic data, but also by the lack of physical models that incorporate age- and sex-dependent variations and tissue heterogeneity. Present calculations assume homogeneous organ composition and do not address heterogeneities that will affect the distribution of energy deposition. The complex geometry of the bronchial airways must be better modeled to determine accurately the radiation dose from inhaled radionuclides, i n particular radon decay products.

22 /

3. DOSE D E T E R F A T I O N

Knowledge of the radiation dose to the bone marrow is particularly important in radionuclide therapy and some occupational and environmental exposures. The dose to bone marrow progenitor cells from beta particles and low-energy electrons must be accurately assessed (NCRP, 1985a; 1985b). Dose estimates to date depend on a single computer model. Completely independent computer algorithms should be developed to verify the single algorithm that has been used for almost all calculations of dose from internal emitters. The algorithms must be improved to increase the range of particle energies considered (NCRP, 1989).

3.2.2 Development of Improved Calculational Models for Relating Exposure to External Radiation Fields The present models used for determining doses to organs from external radiation fields do not completely take into account the variation among individuals in age and anatomy, the complex geometry of internal structures and the heterogeneity of tissues. Because of this, there is still a large uncertainty in the dose calculated from these models for any speci.6~individual. Calculational models have been developed by the International Commission on Radiation Units and Measurements (ICRU, 1985; 1988) to relate specifically defined, measured radiation quantities to the dose. However, the measured quantities include energy-dependent quality factors for neutron radiation, and in general they greatly overestimate the dose for both photon and neutron radiation. External exposure to high-energy particles is not addressed. There is a need for further development of calculational algorithms that relate the fundamental field quantity of energy fluence to absorbed dose, especially for neutrons and HZE particles (including secondary neutrons resulting from HZE particle interactions). These models must include methods to account for age- and sex-dependence, tissue heterogeneities and complex internal geometries. I n medical diagnostic applications, there is a need for accurate dosimetry taking into account

3.2 PHYSICAL DOSIMETRY MODELS

1 23

variations in organ size based on computed tomography. In terms of accurate bone-marrow dose, changes in the distribution of active marrow with age need to be assessed.

3.2.3

Relationship of the Microscopic and Submicroscopic Distribution of Energy Absorbed to the Risk of Radiation Injury

There is a need to understand the relationship between microscopic and submicroscopic energy distribution from radionuclides in the body and the dose quantity most appropriately related to risk. This relationship may be most applicable to low-energy electrons and alpha particles from internally deposited radionuclides. A limited number of studies have demonstrated that the microscopic distribution of energy deposition is more descriptive of risk than is the average energy deposition. In particular, these investigations have involved the incorporation into DNA of the low-energy beta emitter 3~ and the Auger-electron emitter 125~.Other studies have shown that the distribution of an alpha-particle emitter in the testis (and thus the distribution of energy deposition) can affect the ultimate risk. However, the specification of the appropriate dose quantity to be related to risk remains uncertain. In some cases, particularly for low-LET radiation, an average organ dose may be appropriate. With high-LET particles or very low-energy electrons, risk may be more closely related to the microscopic or submicroscopic energy deposition.

3.2.4

Improvement of the Data Base of Environmental Parameters for Use in Dose Assessment Models

Improvement in environmental dose assessment models depends on having an accurate data base of environmental factors that affect the transport and resultant effects of long-

24 / 3. DOSE DETERMINATION

lived radioactive material. United States agencies have sigd5cantly reduced support for research on the fate and effect of long-lived radionuclides in the environment. Without continued support for the acquisition of information about the basic physical, chemical and biologic processes that occur when these radionuclides reach the environment, improved modeling capabilities and attempts to reduce the uncertainties in these models will be nullified by the use of potentially inaccurate transport parameters. One example is technetium. This radionuclide has a six percent fission yield, a n extremely low affinity for soil and sediment particles, and an extremely high degree of bioavailability, and thus it is a unique component of the nuclear fuel cycle. Significant quantities of technetium are present in soil and ground water a t sites where fuel is reprocessed. However, unlike most of the radionuclides associated with reprocessed fuel, technetium has been identified a s presenting more of a risk a s a chemical toxicant than a s a radiological hazard. I t interacts as a sulfur analog in metabolic and chemical processes. This can lead to the metabolic dysfunction and death of the involved organism. Evidence indicates that this interaction is most pronounced with the complex proteins used i n electron transport: thus in plants, photosynthesis and protein metabolism are d e c t e d . While there is a wealth of information for the soil-plant system, its implications for the subsequent food pathways have been neglected and require attention. Carbon is ubiquitous and of all elements has been the most researched; substantial pool and flux information is available, especially on a global basis. However, there are several important unknowns concerning the fate of gaseous radiocarbon close to release points. These include the rates of equilibration with soil carbonate minerals, the flux rates for photosynthetically fixed radiocarbon to accumulated refractory carbon (including soluble fulvates and humates) and the flux rates for soil-borne radiocarbonates to plant roots. Each of these processes can influence the transport of radiocarbon to humans. Acquisition of these necessary data would reduce the present uncertainty. Additionally, there are questions about the observation that deposited radionuclides such a s ''~r, 1 3 7 ~ s12q , and 14care depleted from the available biosphere more rapidly than can be accounted for by physical decay alone.

3.3 EXPERIMENTAL TECHNIQUES /

25

3.3 Experimental Techniques, Measurements and Instrumentation 3.3.1 Development of Dosimetric Techniques for the Experimental Verification of Complex Calculational Models There is a need to verify the mathematical models used in the calculation of energy deposition distributions and dose in situations that cannot be directly measured, especially relating to internal radiation emitters (NCRP, 1985a). It is also important to substantiate the models for exposure to external radiation that take into account age and sex differences, tissue heterogeneities and complex internal structures. Similarly, the models used to relate measured field quantities to absorbed dose or equivalent dose or effective dose must be validated by some measurement technique. These requirements could result in the development of new radiation measurement and dosimetric devices (including biologic dosimeters) and phantoms.

3.3.2 Development of Accurate and Sensitive Methods for Monitoring Intake Accuracy and sensitivity of monitoring must be improved to assure good radiation safety practice and compliance with current recommendations for annual reference levels of intake. The concept of a 50 year committed effective dose that is currently the basis for many occupational radiation-protection standards for control of internal exposure to radionuclides makes it necessary to detect and to quantify very low annual intakes from in-vivo or in-vitro bioassay samples or from air samples collected in the work area. Although each of these approaches has strengths and weaknesses, all have been impacted by the need to detect and to quantify radionuclides a t levels that are much lower than previously required. Additional research should be directed to the development of more sensitive methodologies for detection and analysis, in order to facilitate these monitoring programs. Also, improved approaches for

26 / 3. DOSE DETERMINATION distinguishing the exposure of interest from background exposures must be developed.

3.3.3

Development of a More Exact Method for Monitoring Uranium Uptake

There is a particular need to develop a more exact method for determining the exposure of individuals to uranium, because the present method is not optimal for regulating chronic exposures. The exposure limit for soluble forms of uranium is based on limiting the peak concentration value for uranium in the kidney to 3 pg g-l of tissue. Although this approach appears to have provided a n overall adequate level of protection to uranium workers, it may not be the best way to control prolonged, or repeated, brief occupational exposures. Chronic exposures might produce dose-response relationships that are different from those related to acute exposures. In turn, this might lead to different health protection approaches for soluble uranium compounds of low specific activity. 3.3.4

Development of a Generic Guidance Document for Environmental Monitoring of Radionuclides and Chemicals

Environmental monitoring is crucial to the assessment of the potential radiation dose resulting from the release of radioactive material to the environment. Guidance is required so that this procedure is performed in a consistent manner that is useful for accurate dose assessment. Over the last four decades a number of strategies have been developed for monitoring the environment following radioactive releases. These testing efforts should be extended to include hazardous chemicals. Thus, there is a requirement for a guidance document detailing the constitution of a n effective, cost-efficient, environmental monitoring program. Such a document would assist facilities in the development of more defensible monitoring programs, particularly when coupled with a methodology for prospectively evaluating the risks of

3.4 EXPOSURES TO SPECIFIC SOURCES / 27

radionuclides in the environment, as well as a method for demonstrating compliance. 3.3.5

Development of Instrumentation to Relate Radiation Field Quantities to Relevant Dose Quantities

There is a need for instrumentation that can accurately measure radiation field quantities so that the measurements can be related to radiation dose or equivalent dose for purposes of radiation protection. To assess the risk to persons exposed to radiation from external sources, measurement devices are placed on the individual. The response of these devices must then be related to a radiation dose received by the individual or a radiation dose to specific organs of the individual. Although for x-and gamma-ray radiation the response of these devices does not underestimate the effective dose to the individual, there is considerable uncertainty in the actual relationship between the instrument response and the equivalent dose or effective dose to the individual. These uncertainties must be reduced. In particular, for neutron radiation and for HZE charged-particle radiation, better instrumentation is required for measuring dose quantities a t levels necessary for radiation protection. M i c a 1 neutron measurement devices are still very insensitive in the range of energies and intensities that are important for many neutron exposures (ICRU, 1988; NCRP, 1989). 3.4 Exposures to Specific Sources 3.4.1 Development of Accurate Models of the Dose to

Bronchial Tissues from Radon Progeny in Relation to Airborne Radon Concentration There is a need for more accurate modeling of radiation dose

to bronchial tissue from radon progeny and for more accurate methods of relating radon exposure of the general public to the exposure data from studies of underground miners. Additional research is necessary to determine which exposure and response factors for the general population's exposure to indoor radon

28 / 3. DOSE DETERMINATION differ &om those that apply to uranium miners, and how these differences might affect the extrapolated health risk per unit of exposure to radon and its progeny. The relationship between airborne radon and the dose to bronchial tissues &om radon decay products involves many physical and biologic factors, some of which are age- and sexdependent and some of which are dependent on the health status of the individual. In addition to better models, as discussed in Section 3.1, a greater understanding of the physical relationship between airborne radon and the radiation dose to bronchial tissue (e.g., radiation equilibrium, particle size and attachment to aerosols) must be achieved. 3.4.2

Development of Screening Models for Environmental Contaminants

There is a need to improve and further develop screening models that will identify the significant environmental contaminants and assess their contribution to the dose the public receives. Uncertainty analysis must be applied to these models and site-specific testing must be instituted. Many of the tools that are used to produce quantitative risk assessments rely heavily upon the use of computer models. These assessments are subject to large uncertainty. To address this problem it is recommended that intentionally biased screening calculations be developed to eliminate contaminants, and possibly sites, whose contribution to the population radiation dose and risk is clearly trivial. At the same time, these models must clearly identify those contaminants and sites that could pose a significant risk. This methodology should not only allow the decision-maker to set consistent national priorities, but also provide priorities for site-specific remediation. Once additional data on the most important contaminants become available, more realistic models can be employed. It is essential that these models include uncertainty analyses to provide confidence limits on dose and risk predictions and to delineate the exposure pathways and model parameters that contribute most to the uncertainty. These results will then identify site-specfic research essential for testing and improving the reliability of the models and parameters used for risk assessment.

4. Risk Assessment This Section provides a n overview of a number of areas encompassed by risk assessment and highlights particular requirements for more research. The key concerns relate to knowledge about carcinogenesis and, to a lesser extent, genetic effects pertaining to dose-response relationships, the magnitude of effects a t low doses and the effects of fractionation or protraction of exposure. The need for further research is motivated by several considerations: few data may be available or they may be of questionable quality, the uncertainties a s they affect risk may be large, and the exposures may be ubiquitous so that the public health implications may be great.

4.1 Animal Studies a n d t h e i r Relationship t o H u m a n Studies Many human populations are exposed a t the low doses and low-dose rates of interest. These populations, however, are not suitable in size, and their exposure records, etc., are not adequate to obtain precise risk estimates. The need for a precise dose estimate for each individual in the study, and for a very large number of individuals, in order to achieve reliable risk estimates render these studies prohibitively expensive. Also the potential for confounding factors and the possibility of interaction of radiation with other environmental carcinogens make such studies impracticable. In experimental animal studies, radiation dose can be defined and exposure to other agents regulated to a major extent. Moreover, animals can be used to study radiations for which there are not adequate sample sizes of exposed individuals, such a s neutron exposures, internal deposition of plutonium, etc. Additional discussion of animal experiments involving high-LET radiation is given in Section 4.3.

30 1 4. RISK ASSESSMENT

4.1.1

Species Dose-Response Differences a t the Tissue, Cellular and Molecular Levels

To maximize the use of dose-response data obtained in nonhuman biologic systems, additional research should be devoted to establishing stronger links among studies conducted in humans, in different species of laboratory animals and a t the tissue, cellular and molecular levels. It is well known that different dose-response relationships for internally deposited radionuclides can occur among various species including humans. Recognizing that much of our current knowledge in this area has been derived from studies in nonhuman systems, it is then necessary, in the extrapolation process from animals to humans, to understand and account for these dissimilarities which can arise a s a result of dosimetric differences among species and from variations i n the types and degrees of biologic response. New techniques applied to studies a t the tissue, cellular and molecular levels are facilitating a deeper understanding of the bases for species differences that should enhance our ability to combine dose-response data from diverse sources to obtain better health-risk estimates for people exposed to internally deposited radionuclides.

4.1.2

Integration of Animal and Human Data to Provide the Best Estimates of Dose-Response, Relative Biological Effectiveness and Dose-Rate Effectiveness Factor

Several principal issues of radiobiology, e.g., dose-response curves, Relative Biological Effectiveness (RBE) and Dose-Rate Effectiveness Factor (DREF), deserve a thorough analysis based on all available data. There is a need to develop reliable methods, or improve existing ones, to factor in the body of knowledge derived from studies of mammalian radiobiology and carcinogenesis, and to apply it to human cancer and genetic risk estimation. Some of this work has been done, e.g., Storer et al. (1988). Data sets from certain mouse experiments have been analyzed by sophisticated methods. Other available data sets should be reviewed to see if there is a n opportunity for further analyses. This may require the development of new

4.1

STUDIES / 31

methodological approaches, in both modeling and integrating the animal data and in extrapolating radiation risks from animals to humans.

4.1.3 Studies in Animal Systems to Validate Mathematical Models of Radiation-Related Carcinogenesis

A goal in modeling data from animal studies is to make the transition from a n assumption of mechanisms to models based on mechanisms that are biologically realistic. There is a continuing need for making models of carcinogenic doseresponse relationships more realistic in terms of knowledge about mechanisms. Many models of carcinogenesis suggest a multistage process. Few measurements have been taken to provide data on cellular and molecular changes during the early stages of carcinogenesis that could elaborate or validate models. Some data that could be useful in model validation are modifications of cell proliferation, karyotypic alterations and activation or inactivation of oncogenes and other growthregulating factors. Data on the effect of inflammation or immunologic changes on cell types, proliferation and differentiation observed during early stages of carcinogenesis can also provide useful input into models of carcinogenesis.

4.1.4

Determination of the Influence of Parental Exposure on Leukemia Risk in Offspring

A recent report (Gardner et al., 1990) has suggested that children of fathers who worked in a nuclear reprocessing plant have an increased risk for the development of leukemia if the fathers received more than 10 mSv in the six months before conception of the children andfor more than 100 rnSv in preceding years. An attempted replication of this study at another nuclear facility did not confirm these findings (Urquhart et al., 1991). However, the Urquhart et al. results were not statistically inconsistent with the Gardner et al. hdings. Other studies of leukemia and preconception paternal irradiation have

32 / 4. RISK ASSESSMENT shown mixed results (Buckley et al., 1989; Graham et al., 1966; Hicks et al., 1984; McKinney et al., 1991; Shiono et al., 1980; Shu et al., 1988; Yoshimoto, 1990). The very limited &dings fiom animal research with regard to this issue are also equivocal (Batra and Sridharan, 1964; Kohn et al., 1965; Nomura, 1982;Vorobstova, 1989). Additional human and animal studies are needed to clanfy the presence, nature and magnitude of possible risks &om preconception irradiation.

4.2 Human Epidemiologic Studies of Low-LETExposures

This Section provides a n overview of the areas of research encompassed by radiation epidemiology and highlights those in which there is a need for more work. In all areas of research in radiation epidemiology, i t is important to consider carefully the value of potential (or completed) studies. Several elements enter into this consideration, and if one or more is lacking, the study is of limited value even though the topic may be of high interest. The elements include: Can the pertinent individual exposures or doses be adequately characterized, and do they have a s f i c i e n t range so a s to be informative? Will the combination of dose, number of persons and length of observation be sufficient that effects are likely to be seen, i.e., does the study have adequate statistical power? Is there enough ancillary information available to check on or control for important covariates of risk? Do the study design and the data collection methods avoid potential biases in subject selection or information acquisition, and are the measures employed sufficiently reliable? Have the primary hypotheses and analyses been specified in advance, so that a "fishing expedition" is avoided in the data analysis phase? For completed studies, have they been interpreted in a balanced fashion and in the light of other available data?

4.2 HUMAN EPIDEMIOLOGIC STUDIES

4.2.1

/ 33

Improvement of Estimates of the Risks from Exposure to Low-Dose and Fractionated or Protracted Low-LET Irradiation

Much of the concern about the effects of ionizing radiation pertains to situations where the total exposures are low or where they have been accrued over a period of weeks or years. There is a large range of uncertainty about the relative amount of risk from such exposures when compared with acute, highdose radiation. Thus, information on DREFs is of critical importance. A s a basis for estimating DREFs, studies i n which the radiation exposure is fractionated or protracted should be contrasted with those i n which similar doses are received acutely, provided the cumulative doses are s f i c i e n t l y high to be informative. Careful parallel analyses of low-dose-rate studies and high-dose-rate studies may provide the best opportunity for such comparisons. For example, a recent analysis of three occupational radiation studies gave results consistent with the atomic-bomb survivor data, but a dose-rate effect could not be eliminated. The differences are not statistically significant and do not yet contribute to a resolution of this issue (Gilbert et al., 1989).

4.2.2

Development ofAdditional Information on the Temporal Expression of Radiation-Induced Cancer

The time-response (latency) of radiation-related carcinogenesis has both practical and theoretical implications and, a t present, our knowledge is very incomplete. Assumptions about latency have an impact on lifetime risk projections. In recent years, the risk assessment community has been shifting from using the absolute risk model for projecting lifetime radiation risks to using the relative risk model for most cancer sites, which tends to fit the existing data better The constant (over time since irradiation) relative risk model predicts higher risks for the remaining, a s yet not observed, lifetime than does the absolute risk model. This is particularly pronounced for those exposed very early in life. Several recent

34 / 4. RISK ASSESSMENT

analyses of epidemiologic radiation data have suggested that a constant relative risk model may overestimate risk a t longer follow-up times (and older ages), but the results are uncertain. For the major cancer sites, there is a need to analyze all available irradiated cohorts and to pursue additional years of follow-up to better estimate the temporal pattern of risk. Discontinuance of follow-up of any of the several dozen major groups that have been studied is shortsighted, because the scientiiic information from a cohort increases substantially with longer follow-up time. The atomic-bomb survivors exposed early in life and now reaching ages of 40 plus have had a substantial impact upon the recent revisions in risk estimates, so further follow-up of these groups is particularly important to determine whether the high relative risks continue unabated or decline at older ages (Shimizu et al., 1988). Continued follow-up of those in the Japanese atomic-bomb study irradiated in utero will also be valuable.

4.2.3

Development of Better Methods for Transfer of Risk Estimates Across Populations

The scientific guidelines for transferring risk estimates from one population to another with different characteristics are not well developed. This is particularly important since risk coefficients derived largely on the strength of the Japanese atomic-bomb data have to be transferred to American and European populations where different cancer rates (e.g., stomach cancer) and age-dependencies (e.g., breast cancer) prevail (Land and Sinclair, 1991). Methodological work is needed to evolve additional statistical methods or to evaluate the circumstances in which alternative methods would be preferable. I t is also important that expert groups developing risk estimates consider more comprehensively the full range of data sets available from various populations in deriving and evaluating risk estimates. This will help assure compatibility in the transfer of risk estimates from one population to another.

4.3 RISK ASSESSMENT OF EXPOSURE 1 35

4.2.4

Development of a National Dose Registry of Radiation Workers

A comprehensive and integrated registry of individual occupational radiation doses would be very valuable both for worker protection and for preliminary epidemiologic purposes. An example of such a system is the National Registry of Radiation Workers in the United Kingdom. The present ad hoc system of documenting previous worker radiation exposures is inefficient, expensive and often misleading. Especially if "assigned" doses are mandated when past doses cannot be documented. A national dose registry should be designed to largely obviate such assigned doses and this would facilitate epidemiologic studies of radiation workers and assist in controlling workers' cumulative lifetime exposures. Developing accurate rosters of workers and their doses is currently a very expensive proposition and a registry should largely automate such a task.

4.3 Risk Assessment of Exposure to Internal

Radionuclides and Heavy, Energetic High-LET Particles

4.3.1

Life-Span Studies of Dose-Response Relationships for Internally Deposited Radionuclides in Laboratory Animals

Major life-span studies of dose-response relationships for internally deposited radionuclides in laboratory animals, especially those i n a long-lived species, should be followed to completion with a degree of intense scrutiny and analysis comparable to that accorded the human studies which are, of necessity, more limited in scope. Because of the small number of radionuclides and routes of exposure available for study in human populations, much of our knowledge of dose and dose-response relationships for many radionuclides, and the factors that can modify these

36 /

4. RISK ASSESSMENT

relationships, come &om laboratory studies. Detailed analysis and modeling of the results of such studies will provide a stronger basis for recommendations concerning radiation protection and for the conduct of future studies directed a t identifying underlying mechanisms of radionuclide-induced cancer. 4.3.2

Studies of Human Populations Exposed to Internally Deposited Radionuclides Medically Administered

It is of major importance that studies of human populations that have had known exposures to internally deposited radionuclides, such a s medicafiy administered 2 3 2 ~ h2, 2 4 ~ora 13'1, be continued to ensure completeness of follow-up, especially for the individuals exposed a t low-to-moderate levels where there is the most uncertainty about the magnitude of radiation risks. Because these exposures resulted primarily from past medical practices, the populations represent a unique, current opportunity for study that may not be available in the future. It is critical that these studies be pursued to completion to ensure that maximum scientific benefits are derived from the available subjects. 4.3.3

Improvement of the Estimates of Risk from Radon Exposure

Radon is a very important issue from both a health and an economic viewpoint. When expressed on the basis of the total average effective dose equivalent received by the United States population, exposure to radon and its progeny is the largest apparent contributor. The BEIR IV Committee (NASNRC, 1988) made a number of recommendations regarding radon research with which this Report agrees. Briefly, they are:

"... provide more information on the interaction between smoking and radon exposure; and, with improved dosimetry, narrow the uncertainties in the application of lung-cancer risk data derived from miners to the estimation of risk in the

4.3 RISK ASSESSMENT OF EXPOSURE / 37

general population. Collecting and reporting smoking data on these miners should be an essential part of the study design." "... continued epidemiological study, with parallel multivariate analysis, of the temporal expression of lung cancer in underground miners exposed to radon progeny." "F'urther studies of dosimetric modeling in the indoor environment and in mines are necessary to determine the comparability of risk per WLM (working level month) in domestic environments and underground mines." "... continuation of epidemiological studies of lung cancer and other health outcomes resulting hom indoor radon exposure; such studies must have sufficient statistical power to quantify any significant differences between the risks in environmental and occupational settings." Several related comments and recommendations can be added. Studies of additional miner populations would be valuable if they have well-characterized, sufficient person-year sieverts of exposure for adequate statistical power and reliable smoking histories. Many of the present studies are weak in one or both of these attributes. Also, investigation of an inverse dose-rate effect for the alpha radiation involved should be considered. Although the BEIR IV Committee (NAS/NRC, 1988) made advances in risk estimation by assessing risk horn several studies and by delineating the factors that may modify risk (e.g., age a t exposure, dose rate, time since exposure, smoking history), there is a need to conduct analyses of additional miner data sets to increase the precision and ensure the generality of the risk estimates and their modifiers. I t would also be useful to conduct uncertainty analyses in radon exposure estimates, smoking estimates, etc. Several particular questions need to be addressed: What are the cells a t risk for lung cancer h m radon progeny? What is the impact of the radon progeny equilibrium factor upon dose to the lung?

38 /

4. RISK ASSESSMENT

How does the risk following childhood exposures compare to the risk from exposures a s an adult? [The Chinese tin-miner study may provide valuable information on juvenile exposures (Lubin et al., 1990)l. It is important to determine the degree of difference between the exposure and response factors for exposures of the general population to indoor radon and those for miners and how much these differences might alter extrapolated health risks. Similarities and differences among exposures in the mine, home, school and workplace need to be evaluated as to the temporal and spatial patterns by which the radiation dose is received, since these factors may alter the biologic effects and doseresponse relationships. A number of studies of residential radon exposure and lung cancer are ongoing. These studies are expensive and difficult and many suffer &om various weaknesses (e.g.,limited exposure assessments). When more are undertaken, the populations should be chosen selectively. Important selection criteria are: a potential for good historical exposure assessment and an adequate population fraction a t higher exposure levels, adequate smoking histories and Limited population mobility (in order to permit the assessment of radon exposure levels in residences over the entire lifetime). When the several residential studies currently underway have been completed, it is essential to conduct parallel analyses to obtain the most accurate assessment of risk. The comparative findings also will help identify important gaps in our knowledge or unresolved questions. New studies can then be targeted to reduce these uncertainties. 4.3.4 Improvement of Estimates of Risk for

131~

An unresolved issue of importance to the radiation protection community is the magnitude of thyroid-cancer risk from 13'1 for people exposed a s children and adults. More human data are needed, especially among those irradiated with 1311 a s children,

4.3 RISK ASSESSMENT OF EXPOSURE /

39

since the current thyroid cancer risk estimates are based mainly on studies of childhood exposures to external radiation and the limited age data for external exposure suggest that children's thyroid glands have greater radiation sensitivity than adult glands. The present data on the carcinogenicity of l3'1 exposures in children or animals are sparse. Children subjected to fallout from the Chernobyl accident may represent an important population to study for thyroid neoplasia. This population is large and the thyroid doses range up to several tens of Gy (IAEA, 1991). 4.3.5

Determination of the Biologic Effects of Radiation in Space

The biologic effects of HZE particles are much less studied than those of lighter particles, e.g., electrons, photons and protons. Of particular interest are probabilistic endpoints such a s carcinogenesis and deterministic endpoints such as central nervous system damage. The relative biologic effectiveness of these particles for cancer production in animals and mutagenesis i n cell systems must be determined. Also, whether the underlying mechanisms for the action of HZE particles are the same a s those for light particles needs to.be resolved. I n the case of central nervous system damage, the production of microlesions (i.e., a central core of cells killed by the dirBct effects of HZE particles and a surrounding shell of cells damaged by secondary radiation) needs to be reexamined and whether such lesions could critically damage a vital center in the brain investigated. Of particular interest is how well the radiation damage caused by HZE particles is repaired, especially in neurons, and whether late "break down" occurs. Lastly, the interaction of effects of radiation and microgravity need to be analyzed. 4.3.6 Determination of the Relative Biological Effectiveness of Neutrons in Humans

The question of the RBE of neutrons is of some practical concern because of occupational neutron exposures. Attempts to

identify neutron-exposed populations that might be appropriate for epidemiologic studies of cancer, however, have met with little success. Neutron doses to Chinese oil well loggers were much too low to provide information about the carcinogenicity of neutrons (Inskip et al., 1991). Preliminary follow-up data of patients given neutron therapy for cancer have been generally negative, reflecting, perhaps, the fact that neutron exposure to small volumes of tissue results more in cell-killing than cell transformation (Boice, personal communication, 1993).Although the revised DS86 dosimetry for the atomic-bomb survivors indicated that the neutron exposure in Hiroshima was much less than earlier thought, recent data based on neutron activation measurements (Straume, 1992) and chromosome aberrations (Stram, 1992) suggest that neutron exposure in Hiroshima may have been underestimated. If so, then the atomic-bomb survivor data might, in the future, provide information on the RBE of neutrons in humans. 4.4 Improvement of Epidemiologic Methods a n d Applications

A number of suggestions for improvement of epidemiologic methods and for application of epidemiologic results can be listed synoptically, some of which have been touched on in other sections a s well. Pooled analyses have the potential to provide more insights into radiation effects and more precise estimates of risk. They may aid in developing a better understanding of the relationship between radiation effects and complex phenomena that modify the risk. The increased precision of the pooled data sets, compared with individual studies, might permit the examination of various important parameters in more detail and with more confidence. Parameters that might be examined include (but are not limited to): the shape of the dose-response curve; the slope of the linear component of the curve; the temporal pattern of risk, possibly as modified by age; variations in risk associated with dosefractionation or dose-protraction as compared to acute highdose exposures; modification of risk by sex, age, lifestyle

4.5 ELABORATION OF RISKS

/ 41

factors, etc. An evaluation should be made of the available data sets to determine those that would provide better data if they were pooled than they do individually. In pooled analyses, some studies may afford the opportunity of examining comparability by country or ethnic group. Attention should be given to the best way(s) to transport risk estimates from one population to another. The absolute and relative risk projection models should be compared with respect to sex and other factors in association with the transfer of risks from one population to another. Some attention should be given to statistical issues involved in the temporal and dose relationships for protracted exposure, e.g., those associated with long-lived internal emitters. Further techniques should be developed that allow appropriate adjustment for errors in dose measurement or other uncertainties associated with the data. Better methods for assessing uncertainties in lifetime-risk estimates resulting from inappropriate model assumptions such a s the wrong DREF, the wrong transport model, etc., should be created. Mathematical models that attempt to describe the biologic processes of cancer, e.g., the Moolgavkar-Knudson model (Moolgavkar and Knudson, 1981), rather than just the performance of curve-fitting may provide new insights into radiation-induced cancer risks and, therefore, improve the estimate of risk. It is important that the most sensitive and informative statistical procedures available be applied to all studies. Not to analyze the data well is extremely wasteful since data collection is so expensive, while good quality analyses usually add little cost relative to the cost of data collection.

4.5 Elaboration of Risks by Studying Host Susceptibility Factors Determining host factors that identify especially sensitive subpopulations is very important for radiation protection and is also likely to provide insights for understanding radiation

42 / 4. RISK ASSESSMENT

carcinogenesis (see Section 2.2). This is, therefore, a n issue of some importance, but biomarkers must be developed for detecting cancer (or other disease) susceptibility before meaningful studies of carriers can be conducted. 4.6.1

Development of Models that Provide Individualized Molecular Risk Assessment for Cell Survival a n d Carcinogenesis

Extensive efforts have been made to develop predictive models for cell survival following radiation exposure. These models have rarely included experimentally derived biochemical parameters, e.g., rate constants for the function of repair enzymes. As such biochemical information becomes available, it should be utilized in the development of biologically based radiation-response models. This is perhaps most important in the development of models of radiation-induced carcinogenesis, where the physical aspect of the radiation exposure is the best understood variable in the outcome. I n the carcinogenic process, the intervening stages between the deposition of energy in the affected cell and the endpoint of tumor development are dependent on a series of biochemical events each with an associated Likelihood of occurrence. Efforts to develop models of carcinogenesis and mutation should aim to determine which of the experimentally observed biochemical changes are crucial to the outcome in question (see Section 2.3.).

4.6.2

Characterization of Radiutwn Risks in Relation to Host Susceptibility Factors and Age at Exposure

The development and function of the immune system may be altered by radiation exposure. Differences in immune competence have been defined among individuals with genetic disease. Other subclinical differences exist i n some fractions of the population. The role these subclinical differences play in individual sensitivity for development of radiation-induced cancer needs to be defined. There is evidence that in-utero irradiation may alter the development of the immune system. I t

4.6 RADIATION AND OTHER TOXICANTS /

43

is important to determine whether this alteration can affect the frequency of radiation-induced cancer. There is considerable information &om human and experimental data sets with regard to the degree to which age a t exposure to ionizing radiation modifies the risk for various cancer sites. The BEIR V Committee (NAS/NRC, 1990) found age-at-exposure effects for numerous cancer sites including leukemia, breast cancer, digestive cancer and "other cancers." Age-at-exposure effects among the other tumor sites were statistically unreliable because of the small number of cancer deaths involved. The mechanism of suppression of tumor expression for many years following exposure and why it occurs for a longer period of time, for some cancer types a t least, when radiation is received a t a younger age are interesting radiobiologic problems. A special case of age a t exposure pertains to prenatal irradiation. I n addition to developing estimates of cancer risk fkom in-utero irradiation, two new concerns over prenatal irradiation have recently surfaced that require further study: intelligence deficits associated with irradiation primarily during weeks 8 to 15 of gestation (see Section 2.7), and the possible association between leukemia and preconception irradiation which was suggested by a recent study of residence near Sellafield Nuclear Power Station (Gardner et al., 1990) (see Section 4.1.4). It is important to evaluate the utility of studying a given population for host susceptibility factors or interactions among factors. A situation i n which the radiation dose is low, and hence the magnitude of effect is low, would not likely be useful for delineating factors that modify the radiation effect. Resources should be invested only in studies that have reasonable prospects of yielding meaningful results. 4.6 Interactions of Radiation and Other Toxicants

Humans are exposed to mixtures of chemicals, drugs and radiation. It is important to determine whether the biologic responses h m these combined exposures can be predicted. Because there are many potential types of chemical exposure in the environment and wide ranges of radiation exposure

44 1 4. RISK ASSESSMENT

aequences and dose patterns, it is not feasible to conduct studies that will address all potential interactions. However, short-term cellular and molecular techniques allow evaluation of a wide range of different exposure conditions. Chemicals and types of radiation exposure with potential for antagonistic or synergistic interactions can be identified for further investigation. With cellular and molecular approaches, mechanisms of interaction can also be examined. This level of understanding can help in extrapolation from individual chemicals or types of radiation to combined exposures. Few interactions of radiation and other agents have been identified in human studies to date, perhaps because large populations with substantial exposure to both radiation and some other specific toxicant are uncommon. Some epidemiologic information is available concerning the joint effects of smoking and radiation exposure upon lung-cancer risks, ultraviolet and ionizing radiations upon skin-cancer risks and cancer chemotherapy and radiation exposure upon various secondcancer risks. All of these interactions have been rather crudely defined and more information is needed. Other agents which are likely candidates for epidemiologic study based on laboratory research or other considerations include asbestos, extremelylow-frequency electromagnetic fields and heat.

5. Prevention, Intervention and Perception 5.1 Prevention Prevention starts with a n understanding of who is a t risk and of the factors that amplify their risk.

5.1.1

Utilization of Molecular and Cellular Techniques to Identify Individuals Who May Have an Increased Risk for Radiation-Induced Cancer

Certain individuals are hemizygous for tumor-suppressor genes. Thus, single deletions of the remaining active gene may result in cancer development. Tumor-suppressor genes have been identsed that are associated with the induction of various malignancies such as the Rb gene in retinoblastomas and osteosarcomas, the WT-1gene in Wilm's tumor, the p53 gene in bladder, liver, breast, lung, colon and other cancers and the APC gene i n colorectal cancers. Additional research is required to establish the presence of other tumor-suppressor genes that may be associated with other types of cancers and genetic diseases. Molecular techniques can be developed to determine sensitive human subpopulations. Standards might then be set to limit radiation exposure of sensitive subpopulations (see Section 2.2).

6.1.2 Relationship of Patient Dose to Radiologic Image Quality and Diagnostic Outcomes Poor quality radiologic examinations result in little, or no, benefit to the patient while exposing the patient to a potentially

46 / 5. PREVENTION. INTERVENTION AND PERCEPTION significant radiation dose and its attendant risk. The technical and diagnostic accuracy of imaging i n radiology is a n area that could benefit from research evaluating the efficacy of the imaging procedure and examining potential actions to reduce the collective dose to the general population.

6.1.3 Assessment of the Impact of New Technologies a n d Changing Demographics on Risks from Medical Radiation Sources Three factors may contribute to increases in annual and lifetime per capita doses to the population. In some cases, these doses can be translated into a higher risk of induced malignancies. The factors are: the salvaging of very low birth weight infants on whom multiple diagnostic and therapeutic procedures are performed, primarily after birth, but in some cases in utero, the increased use of computed tomography and interventional radiology techniques for diagnosis andlor therapy with associated increases in gonadal and marrow doses, and the increasing life expectancy of the population, many of whom will live long enough that greater risk results, for a given dose, due to the increased period of expression. On the basis of risk estimates made in 1985 and exposure values from 1977, previous work indicated that less than one percent of all breast cancers and one percent of all cases of leukemia resulted from diagnostic radiology and that the highest incidence for these occurred at ages 76 and 69, respectively (Evans et al., 1986). I n terms of research, further efforts should be made to estimate the magnitude of radiation exposure from diagnostic and therapeutic sources and to use these with updated risk estimates to determine the magnitude of induced cancers under present conditions.

5.1 PREVENTION /

6.1.4

47

Acquisition of Additional Data on Dansmission, Scattering and Fragmentation That Will Help in the Development of Better Shielding

The need for research in radiation shielding arises primarily from a reduction in radiation-dose design standards that have been recommended under revised protection guidelines (NCRP, 1993). Substantial work will be required to verify existing calculational models, develop new models and evaluate various existing and potentially new construction models. This information will be important in optimizing the design of facilities, e.g., medical and industrial facilities and shielding for spacecraft, to provide suitable shielding for radiation protection while controlling cost and space requirements to reasonable values. I t has been pointed out that the error (overestimation) in tenth value layer for leakage radiation from a 10 MeV electron accelerator may be a s much a s 50 percent (Tochilin and LaRiviere, 1979). This could lead to substantial overshielding and a cost overrun of $10,000 or more, depending on the facility. Including a safety factor of ten in shielding design to account for unknown uncertainties could have similar results. Although much of the necessary information has been determined for materials and energies used in diagnostic radiology, there is a need for better attenuation information for x rays in concrete in the range 50 keV to 25 MeV. This information is required for the different concrete mixes using various aggregates. Because of the reduction in allowable occupational radiation exposures (NCRP,1993), new techniques should be developed for evaluating more accurately the transport of radiation through and around shielding. Currently, estimates of radiation transport through ducts and entrance mazes to radiation facilities are based on a few measurements and use empirical models, generally leading to overdesign of protective barriers. More measurements of neutron and photon scattering and transport are needed a s well as more accurate calculational models in order to design the optimal shielding for facilities. Galactic cosmic rays are the major radiations found in space outside of the magnetosphere. They are composed principally of

48 / 5. PREVENTION, INTERVENTION AND PERCEPTION protons (87 percent) and helium ions (12 percent). A small but significant remaining component is HZE particles, of which iron is thought to be the most important. The penetration of these HZE particles into spacecraft may cause fragmentation of the particles with the production of secondary particles. These secondary particles may be an important source of radiation for missions deep in space. In order to better estimate the doses likely to be received by those exposed during these flights, more information is required about the fragmentation of iron and other heavy particles as they pass through the exterior of spacecraft and about the spectra of the resulting secondary particles. In addition to radiations not normally encountered on earth, space exploration may involve the use of materials that are not normally used in construction on earth. Materials available for use in spacecraft and in potential construction on other planets may be substantially different from those that have been previously evaluated for radiation shielding. 5.2 Interventions

Interventions cover several areas and this Section is partly based on material already discussed in Section 3 on Dose Determination. The development of interventional strategies can be based on experience with previous radiologic accidents. 5.2.1

Development of Information on Countermeasures Following Large Radiologic Accidents

The information being released on the experiences a t Chelyabinsk and Chernobyl indicates how important postaccident countermeasures are in mitigating health and environmental problems and how little we know about their efficacy. While considerable research was conducted in the United States on countermeasures in the case of nuclear war, this research was never validated. The events in those countries subjected to Chernobyl fallout, provide an opportunity to examine the model predictions and to compare them with data from the accident. The areas of importance are those related to

5.3 PERCEPTION AND PUBLIC POLICY /

49

the urban environment, such as indoor reduction of inhalation and external dose, particle-size deposition rates inside and on building surfaces and decontamination techniques for buildings, roads, gardens and parks. Considerable data are also available on variations in particle deposition on different agricultural crops, translocation, resuspension, rainsplash, rates of transfer to animal products and subsequent elimination. An additional area for study is the agricultural practices that were employed to reduce the accumulation of long-lived radionuclides in agricultural products. Correlation of these data should lead to the development of a generic plan for implementing countermeasures and clean-up activities following a nuclear accident. 6.2.2 Development of Informational Materials for Public Use after a Radiation Accident Experiences a t Three Mile Island- and Chernobyl have indicated the need for better educational materials for the public following a radiation accident. This material should cover several items, including the nature of the accident (see Section 5.3 on approaches to describing the risks associated with the accident), safe living practices (e.g., eating, drinking, traveling) and information on the availability of social support and counseling mechanisms. The optimum source of this information (e.g., a member of the radiation protection community or a lay person) and the factors that will maintain the confidence of the public in the source of this information should be determined.

6.3 Perception and Public Policy A greater, more systematic effort to develop a thorough understanding of public perceptions of radiation risks and adequate methods for communicating these risks is needed. From the technical perspective, much effort and many resources have been spent to discover and assess risks. Only a small fraction of the effort has been devoted to obtaining knowledge needed for managing risks in the public domain. I t is important to begin to address this imbalance.

50 / 5. PREVENTION, INTERVENTION AND PERCEPTION

5.3.1

Development of Common Expressions of Risk

Assessments that quantify health and environmental risks are essential to ensure that remedial actions are cost effective and to compare and evaluate alternatives. Often, past assessments have been limited solely to examining regulatory compliance regarding permissible dose, exposure and concentration. Risk evaluation is the only meaningful way to compare potential exposures to chemicals and radionuclides. Unfortunately, risk conversion factors for radionuclides and chemicals are neither derived nor interpreted in a consistent manner. When the bases for chemical risk factors and radionuclide risk factors are examined, it is evident that they do not have common points for comparison nor are they based on similar exposure time periods. Risk factors for chemical carcinogens are usually derived from laboratory studies in the absence of human data and represent the upper 95 percent extrapolation for the occurrence of excess cancer incident, assuming a lifetime exposure. This lifetime exposure is usually taken to be 70 years. Risk factors for radionuclides are derived from best-estimate extrapolations from extensive human data, but represent only the incidence of fatal cancer. To be meaningful, risk factors need to be developed that reflect common endpoints. An appropriate endpoint might be a weighted lifetime risk of developing cancer with fatal cancers receiving a higher weight than nonfatal cancers. 5.3.2

Development of a Better Understanding of the Public's Perception of Risk and Improved Methods of Presenting Information on Exposure and Risk

It appears that individuals do not easily understand small risks, make systematic errors in evaluating small versus large risks and may be swayed to make choices regarding the magnitude of risk depending on the analytic presentation of the information. Some of this was summarized in NCRP Proceedings No. 1, Perceptions of Risk (NCRP, 1980); other material is presented in the publications of Bell et al. (1988), Starr (1969) and others. Further basic work in cognitive

5.3 PERCEPTION AND PUBLIC POLICY /

51

psychology will increase our understanding of how members of the public evaluate risks. In the context of radiation protection, several specific research applications should be encouraged. These are: assessment of factors that contribute to the public's misunderstanding of either the magnitude or impact of radiation exposure; development of better ways to express exposures, particularly in relation to natural background or to accepted exposures from other sources (environmental, occupational health, etc.); development of better methods to teach probabilistic concepts to students and other members of the general public. The evolution of improved methods to describe risks may depend upon gradually increasing the ability of students a t all levels to understand probabilistic concepts, ranging from an understanding of a simple probabilistic event to an understanding of more complicated situations (conditional events, conjunctive or disjunctive situations, etc.). Although students are sometimes exposed to these concepts a t the high school level and more frequently a t the college level, current approaches fail to give them an intuitive understanding of probabilistic events. 5.3.3

Assessment of Societal Values with Respect to Radiation and Other Risks

Public policies related to risks of any sort depend upon the extent to which a society values gains achieved from risk reduction and supports the costs necessary to achieve these gains. Preliminary information is increasingly available from the field of medicine on the extent to which society is willing to devote resources for particular purposes. Some of this information comes from explicit cost-effectiveness (or less frequently cost-benefit) calculations on the use of particular screening, diagnostic or therapeutic interventions. Some is obtained from extrapolation of these same techniques to decisions regarding the provision of health services. Research on assessing these values and associated willingness-to-pay estimates should be performed for risk reductions related to

52 / 5. PREVENTION, INTERVENTION AND PERCEPTION

medical and environmental radiation sources. Willingness-to-pay estimates should be made with explicit consideration of the effect of such expenditures on other public goods. 5.3.4

Development of a Level of Acceptability for Different n p e s of Risk

Currently there is an inconsistent interpretation of risk limits. For example, the boundaries of acceptable and unacceptable risks need to be defined. For any given situation, there will be a level of risk that can usually be considered clearly acceptable just as there is a level of risk that most individuals would see a s clearly unacceptable. Studies to define levels of risk that are clearly acceptable, clearly unacceptable and a level considered trivial and warranting no further investigation could be very beneficial. Risks occurring between the clearly acceptable and clearly unacceptable levels could then be reduced as far as it is economically, socially and politically practical to do so.

6. Resource Requirements The prosecution of the research identified in this Report will require appropriate resources. These can be defined in terms of people, facilities and data bases. First, the continued flow of young investigators, trained in radiobiology, epidemiology, medical and health physics and environmental sciences into radiation protection and related fields is essential. I n particular, the support of positions at universities, research institutes, teaching hospitals and national laboratories is required to provide a cadre of people capable of addressing the research agenda laid out in this Report and maintaining a response to this national and worldwide need. Second, special facilities are required for the pursuit of this research, e.g., long-term tissue banking units; special animal quarters with radiation sources, shielding and facilities for the handling of radionuclides, a s well a s for caging animals for lifeterm maintenance; irradiation sources including low-dose and low-dose-rate photon fields, particle accelerators and sources of neutrons of proper energies. Third, certain collections of animal and human epidemiologic data must be developed and maintained. These include the completion and recording of animal life-span studies for internally deposited radionuclides (see Sections 4.1 and 4.3); the completion of human studies involving medical (232~h, 224~a, 1311) and occupational ( 2 2 6 ~ a2,2 2 ~and n progeny, and 2389239F'~) radionuclides deposited internally (see Sections 4.3.2 and 4.3.3); the maintenance of registries of radiation workers starting with those working in the nuclear industries (see Section 4.2.4) but ultimately extending to the medical professionals in radiology and nuclear medicine; the establishment of a pilot collection system of dose information from patients; and a compendium of data obtained from large radiation accidents such as Chernobyl. It is difficult to see how this research agenda can be pursued absent the infrastructure described above. Certainly, if the research issues of radiation protection are not addressed, there will be no research strategy designed or proposals formulated.

54 / 6. RESOURCE REQUIREMENTS

Nor can the research proceed without the specialized capital investments that will be required. Moreover, the cost of not completing and storing the data bases now in existence or currently being gathered is enormous and the possibility of recreating them nonexistent or prohibitively expensive. I t is in the interest of those agencies, public and private, that hold themselves responsible for radiation protection to work collaboratively to see that these data bases are completed and preserved. Lastly, a continuing source of funding for the year-to-year support of this research will be needed. I n particular, the continued support of investigator-initiated research is required. I t is the Council's intent that the specifics of this Report provide a rational basis for research allocations in the field of radiation protection.

References ABRdllIAMSON, S., AWA, A.A. and NAKAMURA, N. (1990). "New risk estimates for trisomy induction by radiation exposure," in RERF Update, Vol. 1, Issue 4, pages 3 to 4 (Radiation Effects Research Foundation, Hiroshima, Japan). ANTAL, S., s h R h Y , G., SCHOLTZ, B., UNGER, E. and H I D ~ G I , E.J. (1991). "Neoplasms in mice after irradiation in utero," page 253 in Radiution Research: A lhentieth-Century Perspective, Volume 1: Congress Abstracts, Chapman, J.D., Dewey, W.C. and Whitmore, G.F., Eds. (Academic Press, San Diego). BATRA, B.K and SRIDHARAN, B. (1964). "A study of the progeny of mice descended h m x-irradiated females with special reference to the gonads," Acta Unio Int. Contra Cancrum 20, 1181-1186. BELL, D.E., RAIFFA, H. and TVERSKY,A. (1988). Decision Making: Descriptive, Normative and Prescriptive Interactions (Cambridge University Press, New York). BENDER, MA., PRESTON, R.J., LEONARD, R.C., PYATT, B.E. and GOOCH, P.C. (1989). "Chromosomal aberration and sisterchromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. 11. Extension of age range," Mutat. Res. 212, 149-154. BENJAMIN, SA., SAUNDERS, W.J., LEE, A.C. and ANGLETON, G.M. (1991). "Thyroid neoplasia in dogs after prenatal and postnatal irradiation," page 255 in Radiation Research: A lhentieth-Century Perspective, Volume 1: Congress Abstracts, Chapman, J.D., Dewey, W.C. and Whitmore, G.F., Eds. (Academic Press, San Diego). BOHR, V.A., SMITH, CA., OKUMOTO, D.S. and HANAWALT, P.C. (1985). "DNA repair in an active gene: Removal of pyrimidine dimers h m the DHFR gene of CHO cells is much more efficient than in the genome overall," Cell 40, 359-369. BUCKLEY, J.D., ROBISON, L.L., SWOTINSKY, R., GARABRANT, D.H., LeBEAU, M., MANCHESTER, P., NESBIT, M.E., ODOM, L., PETERS, J.M., WOODS, W.G., et al. (1989). "Occupational exposures of parents of children with acute nonlymphocytic leukemia: A report fmm the Children's Cancer Study Group," Cancer Res. 49, 4030-4037.

56 1 REFERENCES DOBSON, R.L. and COOPER, M.F. (1974). "Tritium toxicity: Effect of low-level 3~~~ exposure on developing female germ cells in the mouse," Radiat. Res. 58, 91-100. DOBSON, R.L., KOEHLER, C.G., FELTON, J.S., KWAN, T.C., WLTEBBLES, B.J. and JONES, D.C.L. (1978). "Vulnerability of female germ cells in developing mice and monkeys to tritium, gamma rays, and polycyclic aromatic hydrocarbons," pages 1to 14 in Developmental Toxicology of Energy-Related Pollutants, CONF771017, Mahlum, D.D., Sikov, M.R., Hackett, P.L. and Andrew, F.D., Eds. (National Technical Information Service, Springfield, Virginia). EVANS, J.S., WENNBERG, J.E. and McNEIL, B.J. (1986). "The influence of diagnostic radiography on the incidence of breast cancer and leukemia," N. Engl. J. Med. 315, 810-815. GARDNER, M.J., SNEE, M.P., HALL, A.J., POWELL, C.A., DOWNES, S. and TERRELL, J.D. (1990). "Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria," Br. Med. J. 300, 423-429. GILBERT, E.S., FRY, S.A., WIGGS, L.D., VOELZ, G.L., CRAGLE, D.L. and PETERSEN, G.R. (1989). "Analyses of combined mortality data on workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant," Radiat. Res. 120, 19-35. GRAHAM, S., LEVIN, M.L., LILIENFELD, A.M., SCHUMAN, L.M., GIBSON, R., DOWD, J.E. and HEMPELMANN, L.H. (1966). "Preconception, intrauterine, and postnatal irradiation as related to leukemia," Monogr. Natl. Cancer Inst. 19, 347-371. GRIFFIN, C.S. and TEASE, C. (1988). "Gamma-ray-induced numerical and structural chromosome anomalies in mouse immature oocytes," Mutat. Res. 202, 209-213. HICKS, N., ZACK, M., CALDWELL, G.G., FERNBACH, D.J. and FALLETTA, J.M. (1984). "Childhood cancer and occupational radiation exposure in parents," Cancer 53, 1637-1643. HUI, T.E., FISHER, D.R., PRESS, O.W., EARY, J.F., WEINSTEIN, J.N., BADGER, C.C. and BERNSTEIN, I.D. (1992). "Localized beta dosimetry of 13'1-labeled antibodies in follicular lymphoma," Med. Phys. 19, 97-104. IAEA (1991). International Atomic Energy Agency. !Zhe International Chernobyl Project, Technical Report, Assessment of Radiological Conseqllencesand Evaluat ion of Protective Measures (International Atomic Energy Agency, Vienna). ICRU (1985). International Commission on Radiation Units and Measurements. Determination of Dose Equivalents Resulting from External Radiation Sources, ICRU Report 39 (International

REFERENCES / 57 Commission on Radiation Units and Measurements, Bethesda, Maryland). ICRU (1988). International Commission on Radiation Units and Measurements. Determination of Dose Equivalents Resulting from External R&t ion Sources-Part 2, ICRU Report 43 (International Commission on Radiation Units and Measurements, Bethesda, Maryland). INSKIP, P.D., WANG, Z.Y. and FEN, Y.S. (1991). "Suitability of Chinese oil well loggers for a n epidemiologic study of the carcinogenic effects of neutrons," Health Phys. 61, 637-640. KOHN, H.I., EPLING, M.L., GUTTMAN, P.H. and BAILEY, D.W. (1965). "Effect of paternal (spermatogonial) x-ray exposure in the mouse: Life span, x-ray tolerance, and tumor incidence of the progeny," Radiat. Res. 25, 423-434. LAND, C.E. and SINCLAIR, W.K (1991). "The relative contributions of different cancer sites to the overall detriment associated with low-dose radiation exposure," pages 31 to 57 in Risks Associated with Ionizing Racliatwn, Annals of the International Commission on Radiological Protection 22, 1 (Pergamon Press, Elmsford, New York). LUBIN, J.H., QIAO, Y.L., TAYLOR, P.R., YAO, S.X., SCHATZKIN, A., MAO, B.L., RAO, J.Y., XUAN, X.Z. and LI, J.Y. (1990). "Quantitative evaluation of the radon and lung cancer association in a case control study of Chinese tin miners," Cancer Res. 50, 174180. MADHANI, H.D., BOHR, VA. and HANAWALT, P.C. (1986). "Differential DNA repair in transcriptionally active and inactive proto-oncogenes: c-abl and c-mos," Cell 45, 417-423. MARTIN, R.H., HILDEBRAND, K., YAMAMOTO, J., RADEMAKER, A., BARNES, M., DOUGLAS, G., ARTHUR, K., RINGROSE, T. and BROWN, I.S. (1986). "An increased frequency of human sperm chromosomal abnormalities after radiotherapy," Mutat. Res. 174, 219-225. McKINNEY, PA., ALEXANDER, F.E., CARTWRIGHT, R.A and PARKER, L. (1991). "Parental occupations of children with leukaemia in West Cumbria, North Humberside, and Gateshead," Br. Med. J. 302, 681-687. MELLON, I., BOHR, V.A., SMITH, C.A. and HANAWALT, P.C.(1986). "Preferential DNA repair of an active gene in human cells," Proc. Natl. Acad. Sci. USA 83, 8878-8882. MENDELSOHN, M.L. (1990). "New approaches for biological monitoring of radiation workers," Health Phys. 59, 23-28.

58

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REFERENCES

MOOLGAVKAR, S.H. and KNUDSON, A.G., JR. (1981). "Mutation and cancer: A model for human carcinogenesis," J. Natl. Cancer Inst. 66, 1037-1052. NAS/NRC (1988). National Academy of SciencesNational Research Council. Health Risks of Radon and Other Internally Deposited Alpha-Emitters, Committee on the Biological Effects of Ionizing Radiations, BEIR IV (National Academy Press, Washington). NASINRC (1989). National Academy of SciencesINational Research Council. Film Bczdge Dosimetry in Atmospheric Nuclear Tests, Committee on Film Badge Dosimetry (National Academy Press, Washington). NAS/NRC (1990). National Academy of SciencesNational Research Council. Health Effects of Exposure to Low Levels of Ionizing Radiations, Committee on the Biological Effects of Ionizing Radiation, BEIR V (National Academy Press, Washington). NCRP (1980). National Council on Radiation Protection and Measurements. Proceedings of the Fifteenth Annual Meeting of the National Council on Radiation Protection and Measurements, Perceptions of Risk, Proceedings No. 1 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). NCRP (1985a). National Council on Radiation Protection and Measurements. The Experimental Basis for Absorbed-Dose Calculations in Medical Uses of Radionuclides, NCRP Report NO. 83 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). NCRP (1985b). National Council on Radiation Protection and Measurements. General Concepts for the Deposition of Internally Deposited Radionuclides, NCRP Report No. 84 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). NCRP (1989). National Council on Radiation Protection and Measurements. Guiaiance on Radiation Received in Space Activities, NCRP Report No. 98 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). NCRP (1993). National Council on Radiation Protection and Measurements. Limitation of Exposure to IonizingRadicrtion,NCRP Report No. 116 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). NEEL, J.V., SCHULL, W.J., AWA, A.A., SATOH, C., KATO, H., OTAKE, M. and YOSHIMOTO, Y. (1990). "The children of parents exposed to atomic bombs: Estimates of the genetic doubling dose of radiation for humans," Am. J. Hum. Genet. 46, 1053-1072. NOMURA, T. (1982). "Parental exposure to x rays and chemicals induces heritable tumours and anomalies in mice," Nature 296,575577.

REFERENCES / 59 PINKEL, D., STRAUME, T. and GRAY, J.W. (1986). "Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization," Proc. Natl. Acad. Sci. USA 83, 2934-2938. RUSSELL, W.L. (1990). "Problems and possibilities in genetic risk estimation," pages 385 to 395 in Biology of Mammalian Germ Cell Mutagenesis, Banbury Report 34 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York). RUSSELL, W.L., CUMMING, R.G., KELLY, E.M. and LINDENBAUM, A. (1978). "Plutonium-induced specific-locus mutations in mice," Genetics 88, 685 (Abs). SAIKI, R.K., GELFAND, D.H., STOFFEL, S., SCHARF, S.J., HIGUCHI, R., HORN, G.T., MLTLLIS, K.B. and ERLICH, H.A. (1988). "Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase," Science 239, 487-491. SCHULL, W.J., OTAKl3, M. and YOSHIMARU, H. (1988). Effect on Intelligence Test Score of Prenatal Exposure to Ionizing Radiation in Hiroshima and Nagasaki: A Comparison of the T65DR and DS86 Dosimetry Systems, RERF TR 3-88 (Radiation Effects Research Foundation, Hiroshima, Japan). SELBY, P.B. (1990). "Importance of the direct method of genetic risk estimation and ways to improve it," pages 437 to 449 in Bwlogy of Mammalian Germ Cell Mutagenesis, Banbury Report 34 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York). SHIMIZU, Y., KATO,H. and SCHULL, W.J. (1988). Life Span Study Report 11 Part 2. Cancer Mortality in the Years 1950-85 Based on the Recently Revised Doses (DS86), RERF TR 5-88 (Radiation Effects Research Foundation, Hiroshima, Japan). SHIONO, P.H., CHUNG, C.S. and MYRIANTHOPOULOS, N.C. (1980). "Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia," J. Natl. Cancer Inst. 65, 681-686. SHU, X.O., GAO, Y.T., BRINTON, LA., LINET, M.S., TU, J.T., ZHENG, W. and FRAUMENI, J.F., Jr. (1988). "A population-based case-control study of childhood leukemia in Shanghai," Cancer 62, 635-644. STARR, C. (1969). "Social benefit versus technological risk," Science 165, 1232-1238. STORER, J.B., MITCHELL, T.J. and FRY, R.J. (1988). "Extrapolation of the relative risk of radiogenic neoplasms across mouse strains and to man," Radiat. Res. 114, 331-353. STRAM, D.O., SPOSTO, R., PRESTON, D., ABRAHAMSON, S., HONDA, T. and AWA, A.A. (1992). Stable Chromosome Aberrations AmongAtomic Bomb Survivors, RERF TR 13-92 (Radiation Effects Research Foundation, Hiroshima, Japan).

60 1 REFERENCES STRAUME, T., EGBERT, S.D., WOOLSON, W.A., FINKEL, R.C., KUBIK, P.W., GOVE, H.E., SHARMA, P. and HOSHI, M. (1992). "Neutron discrepancies in the DS86 Hiroshima dosimetry system," Health Phys. 63, 421-426. TOCHILIN, E. and LaRMERE, P.D. (1979). "Neutron leakage characteristics related to room shielding," page 145 in Proceedings of a Conference on Neutrons from Electron Medical Accelerators, NBS Special Publication 554, Heaton, H.T. and Jacobs, R., Eds. (National Technical Information Service, SpringEield, Virginia). URQUHART, J.D., BLACK, R.J., MUIRHEAD, M.J., SHARP, L., MAXWELL, M., EDEN, O.B. and JONES, D.A. (1991). "Casecontrol study of leukaemia and non-Hodgkin's lymphoma in children in Caithness near the Dounreay nuclear installation," Br. Med. J. 302, 687-692. VOROBSTOVA, I.E. (1989). "Increased cancer risk a s a genetic effect of ionizing radiation," pages 384 to 401 in Perinatal and Multigeneratwn Carcinogenesis, Napalkov, N., Rice, J., Tomatis, L. and Yamaaaki, H., Eds. (International Agency for Research on Cancer, Lyon, France). WATANABE, H., TAKAHASHI, T., TOYOTA, K., TERADA, A.Y., SHIMURA, K. and ITO, A. (1991). "The effects of paternal 252-Cfneutron exposure to their F1 offsprings of mice," page 259 in Radiutwn Research :A Twentieth-Century Perspective, Volume 1: Congress Abstracts, Chapman, J.D., Dewey, W.C. and Whitmore, G.F., Eds. (Academic Press, San Diego). WOLFF, S., AFZAL, V., WIENCKE, J.K., OLMERI, G. and MICHAELI, A. (1988). "Human lymphocytes exposed to low doses of ionizing radiations become re6actory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA," Int. J. Radiat. Biol. 53, 39-47. YOSHIMOTO, Y. (1990). "Cancer risk among children of atomic bomb survivors. A review of RERF epidemiologic studies," JAMA 264, 596-600.

The NCRP The National Council on Radiation Protection and Measurements is a nonprofit corporation chartered by Congress in 1964 to: 1. Collect, analyze, develop and disseminate in the public interest information and recommendations about (a) protection against radiation and (b) radiation measurements, quantities and units, particularly those concerned with radiation protection. 2. Provide a means by which organizations concerned with the scientific and related aspects of radiation protection and of radiation quantities, units and measurements may cooperate for effective utilization of their combined resources, and to stimulate the work of such organizations. 3. Develop basic concepts about radiation quantities, units and measurements, about the application of these concepts, and about radiation protection. 4. Cooperate with the International Commission on Radiological Protection, the International Commission on Radiation Units and Measurements, and other national and international organizations, governmental and private, concerned with radiation quantities, units and measurements and with radiation protection. The Council is the successor to the unincorporated association of scientists known as the National Committee on Radiation Protection and Measurements and was formed to carry on the work begun by the Committee. The Council is made up of the members and the participants who serve on the scientific committees of the Council. The Council members who are selected solely on the basis of their scientific expertise are drawn from public and private universities, medical centers, national and private laboratories and industry. The scientific committees, composed of experts having detailed knowledge and competence in the particular area of the committee's interest, draft proposed recommendations. These are then submitted to the full membership of the Council for careful review and approval before being published.

62 1 THE NCRP

The following comprise the current officers and membership of the Council:

Officers President Vice President Secretary and Treasurer Assistant Secretary Assistant Treasurer

CHARLESB. MEINHOLD S. JAMES ADELSTEIN W . ROGERNEY CARLD. HOBELMAN JAMES F . BERG

Members SEYMOURABRAHAMSON ADELSTEIN S. JAMES PETERR. ALMOND LYNNR. ANSPAUGH JOHN A. AUXIER JOHN W. BAUM HAROLD L. BECK MICHAELA. BENDER B. GORDONBLAYLOCK BRUCEB. BOECKER JOHN D. BOICE. JR. ANDRI~ BOUVILLE ROBERTL. BRENT A. BERTRAND BRILL ANTONEL. BROOKS PAULL. CARSON MELVINW. CARTER JAMES E. CLEAVER FREDT. CROSS GAIL DE PLANQUE SARAHDONALDSON CARLH. DURNEY KEITH F. ECKERMAN CHAM. E~SENHAUER THOMASS. ELY

THOMASF. GESELL ETHELS. GILBERT ROBERTA GOEPP JOEL E. GRAY ARTHURW. GUY Emc J. HALL NAOMIH. HARLEY

WILLIAMA. MILIS DADEW. MOELLER GILBERTS. OMENN LESTERJ. PETERS RONALDPETERSEN J O H N W. POSTON.SR. ANDREW9.POZNANSKI GENEVIEVES. ROESSLER WILLIAMR HENDEE DAVIDG. HOEL MARVINROSENSTEIN F. OWENHOFFMAN LAWRENCE ROTHENBERG DONALDG. JACOBS MICHAELT. RYAN A EVERETTEJAMES, JR. KEITHJ. SCHIAGER R. JOHNSON ROBERTA. SCHLENKER JOHN BERNDKAHN ROY E. SHORE KENNETHR. KASE DAVIDH. S m AMY KRONENBERG PAULSLOVIC HAROLD L. KUNDEL RICHARDA TELL CHARLESE. LAND L TEMPLETON W~LLIAM JOHN B. LITTLE THOMASS. TENFORDE HARRY R. MAXON RALPH H. THOMAS ROGER0. MCCLELLAN JOHN E. TILL BARBARA J. MCNEIL ROBERTL ULLRICH CHARLESB. MEINHOLD DAVIDWEBER FRED k ME'ITLER,JR. F. WARDWHICKER MARVIN C. ZISKIN

THE NCRP 1 63 Homrtwy Members

TAYLOR, Honomry President WARREN K. SINCLAIR, President Emeritus

h U E i r s T o ~S.

RJ. MICHAEL FRY ROBERT0. GORSON JOHN W. HEALY PAULC. HODGES GEORGEV. LEROY WILFRIDB. A ANN A. ALAN MOGHISSI KARL2. MORGAN ROBERTJ. NELSEN WESLEY L. NYBORG CHESTERR RICHMOND HARALD H. ROSSI

WILLIAML RUSSELL JOHN H. RUST EUGENEL SAENGER A. SAGAN LEONARD WILLLAM J. SCHULL J. NEWELLSTANNARD JOHN B. STORER ROY C. moMFsoN ARTHURC. UPTON GEORGEL VOELZ EDWARD W. WEBSTER GEORGEM. WILKENING HAROLD 0.WYCKOFF

Currently, the following subgroups are actively engaged in formulating recommendations: SC 1

Basic Radiation Protection Criteria SC 1-3 Collective Dose SC 1-4 Extrapolation of Risk from Non-human Experimental Systems to Man SC 1-5 Uncertainty in Risk Estimates SC 9 Structural Shielding Design and Evaluation for Medical Use of X Rays and Gamma Rays of Energies Up to 10 MeV SC 16 X-Ray Protection in Dental Oftices SC 46 Operational Radiation Safety SC 46-2 Uranium Mining and Milling - Radiation Safety Programs

SC 46-8 Radiation Protection Design Guidelines for Particle Accelerator Facilities SC 46-9 ALARA at Nuclear Plants SC 46-10 Assessment of Occupational Doses from Internal Emitters

64 1

THE NCRP SC 46-11 Radiation Protection During Special Medical Procedures SC 46-12 Determination of the Effective Dose Equivalent (and Effective Dose) to Workers for External Exposure to Low-LET Radiation Dosimetry and Metabolism of Radionuclides SC 57-2 Respiratory Tract Mode1 SC 57-9 Lung Cancer Risk SC 57-10 Liver Cancer Risk SC 57-14 Placental Transfer SC 57-15 Uranium SC 57-16 Uncertainties in the Application of Metabolic Models Radiation Exposure Control in a Nuclear Emergency SC 63-1 Public Knowledge Radionuclides in the Environment SC 64-6 Screening Models SC 64-17 Uncertainty in Environmental Transport in the Absence of Site S p d c Data SC 64-18 Plutonium SC 64-19 Historical Dose Evaluation Quality Assurance and h a c y in Radiation Protection Measurements Biological Effects and Exposure Criteria for Ultxa~~und EEcacy of Radiographic Procedures Radiation Protection in Mammography Guidance on Radiation Received in Space Activities Guidance on Occupational and Public Exposure Resulting from Diagnostic Nuclear Medicine Pmcedures Radionuclide Contamination SC 84-1 Con-ted Soil SC 84-2 Decontamination and Decommissioning of Facilities Risk of Lung Cancer from Radon Hot Particles in the Eye, Ear or Lung Radioactive and Mixed Waste SC 87-1 Waste Avoidance and Volume Reduction SC 87-2 Waste Classilkation Based on Risk SC 87-3 Performance Assessment

THE NCRP / 65

SC 88 Fluence as the Basis for a Radiation Protection System for Astmnauta SC 89 Nonionizing Electmmagnetic Fields SC 89-1 Biological Effects of Magnetic Fields SC 89-2 Practical Guidance on the Evaluation of Human Exposure to Radiofkquency Radiation SC 89-3 Extremely Law-Frequency Electric and Magnetic Fields SC 90 h u t i o n s in the Management of Patients Who have Received Therapeutic Amounts of Radionuclides SC 91 .Radiation Protection in Medicine Ad Hoc Committee on the EmbryolFetus and Nursing Child Ad Hoc Committee on Council Involvement in Public Deckion Making

In recognition of its responsibility to facilitate and stimulate cooperation among organizations concerned with the scientific and related aspects of radiation protection and measurement, the Council has created a category of NCRP Collaborating Oqgmhtiom. Organizations or groups of organizations that are national or international in scope and are concerned with ScientSc problems involving radiation quantities, units, measurements and effkts, or radiation protection may be admitted to collaborating status by the Council. Collaborating Organhtions provide a means by which the NCRP can gain input into its activities h m a wider segment of society. At the same time, the relationships with the Collaborating Organkitions facilitate wider dissemination of information about the Council's activities, interests and concerns. CollaboratingOrgankitions have the opportunity to comment on draft reports (at the time that these are submitted to the members of the Council). This is intended to capitalize on the fact that Collaborating Organhtions are in an excellent position to both contribute to the identScation of what needs to be treated in NCRP reports and to iden* problems that might result h m proposed mmmendations. The present Collaborating Organizations with which the NCRP maintains liaison are as follows: American Academy of Dermatology American Association of Phyxjickts in Medicine American College of Medical Physics American College of Nuclear P4yaiciana

66 / THE NCRP American College of Occupational and Envimnmental Medicine American College of Radiology American Dental Amxiation American Industrial Hygiene Assmiation American Institute of Ultrasound in Medicine American Insurance Services Group American Medical Association American Nuclear Society American Pediatric Medical Association American Public Health Amxiation American Radium Society American Roentgen Ray Society American Society of Radiologic TechnolOgiets American Society for Therapeutic Radiology and onc~l~gy Asmiation of University Radiologists Bicelectromagnetics Society College of American Pathologists Conference of Radiation Control Program Directore Electric Power Research Institute Federal Communications Commission Federal Emergency Management Agency Genetica Society of AmericA Health Physics Society Institute of Nuclear Power Operatho International Brotherhood of Electrical Workers National Aeronautics and Space Administration National Electrical Manufacturers Association National Institute of Standards and Technology Nuclear Management and Resources Council Oil, Chemical and Atomic Workers Union Radiation Research Society Radiological Society of North America Society of Nuclear Medicine United States Air Force United States Army United States Department of Energy United States Department of Housing and Urban Development United States Department of Labor United States Environmental Protection Agency United States Navy United States Nuclear Regulatory Commission United States Public Health sf3~C-e~ Utility Workers Union of America

THE NCRP / 67 The NCRP has found its relationships with these organizations to be extremely valuable to continued progress in its program. Another aspect ofthe cooperative efforts ofthe NCRP relates to the Special Liaison relationships established with various gwernmental oqganimqtions that have an interest in radiation protection and measurements. This liaison relationship provides: (1)an opportunity for participating organizationsto designate an individual to provide liaison between the organization and the NCRP; (2) that the individual designated will receive copies of draft NCRP reports (at the time that these are submitted to the members of the Council) with an invitation to comment, but not vote; and (3) that new NCRP e&rts might be discussed with liaison individuals as appropriate, so that they might have an opportunity to make suggestions on new studies and related matters. The following organizations participate in the Special Liaison

Program: A u s W Radiation Laboratory C o m t a 1'EnergieAtomique (France) Commission of the Empean Communities D e & m Nuclear Agency Federal Emergency Management Agency International Commission on Non-Ionizing Radiation Protection Japan Radiation Council National Radiological Protection Board (United Kingdom) National Research Council (Canada) Office of Science and Technology Policy Ofiice of Techr~ologyAssessment Ultrasonics Institute (Australia) United States Air Force United States Coast Guard United States Department of Health and Human Services United States Department of Trampartation United States Nuclear Regulatory Commission

The NCRP values highly the participation of these organizations in the Special Liaison Program. The Council also benefits s i g d i d y from the relationships established pursuant to the Corporate Sponsor's Program.The program facilitates the interchange of information and ideas and corporate sponsors provide valuable fiscalsupport for the Council's program. This developingprogram currently includesthe following Corporate Sponsors:

68 / THE NCRP

Ameraham Carporation Commonwealth Edison Consumera Power Company Duke Power Company Eastman Kodak Company EG&G Rocky f i t s Landauer. Inc 3M Public Service El& and Gas C o m p ~ Southern C&rnia Edison Company Westinghouae Electric C!orpmtion

The c 0 d s activities are made +le by the wl~tary contribution of time and effort by its members and participants and the generous support of the following organizations: &fa Corporation

Alfred P. Sloan Foundation Alliance of America. Insurers American Academy of Dermatology American Academy of Oral and M a x i l l o h d Radiology American Association of Physicists in Medicjne American Cancer Society American College of Medical Physics American College of Nuclear Physicians American College of Occupational and Environmental Medicine American College of Radiology American College of Radiology Foundation American Dental Asamiation American Healthcare Radiology A d m i n i s w ~ ~ American Industrial Hygiene Amciation American Insurance Services Group American Medical Association American Nuclear Society American Osteopathic College of Radiology American Pediatric Medical Asmiation American Public Health Amxiation American Radium Society American Roentgen Ray Society American Society of Radiologic Technologists American Society h r Therapeutic Radiology and Ona)American Veterinary Medical Association American Veterinary Radiology Society

THENCRP /

~~universiityRadiologiata Battelle Memorial Institute Canberra Mwtries, Inc. Chem Nuclear Systems Center fix Devices and Radiological Health College of American Pathologists Committee on Interagency Radiation Reaearch and Policy Caordination Commonwealth of Pennsylvania &&me Nuclear Agency Ediaon Electric Institute Edward Mallinckrodt, Jr. Foundation EG&G Idaho, Inc. Electric Power Research Institute Federal Emergency Management Agency Fbrida Institute of Phoephate Research Rlji Medical Systems, U S A , Inc Genetics Society of America Health Effects Research Foundation (Japan) Health Physics Society Institute of Nuclear Power Operatiom James Picker Foundation Martin Marietta Corporation National Aeronautics and Space Administration National Association of Photographic Manuhturem National Cancer Institute National ElManufa-m Amciation National Institute of Standards and T b b Nuclear Management and Resources Council Picker International Radiation Research Society Radiological Society of North America Richard hunabery Foundation Sandia National Laboratory Society of Nuclear Medicine Society of Pediatric Radiology Unitad States Department of Energy Unikd States Department of Labor United States Environmental Protection Agency United States Navy United States Nuclear Regulatory Commkion VlCbmen, Inc.

69

70 / THE NCRP

Initial funds for publication of NCFU? reports were provided by a gmmt h m the James Picker Foundation. The NCRP seeks to promulgate information and recommendations based on leading sciensc judgement on matters of radiation protection and measmment and to foster cooperation among organizations concerned with these matters. These efforts are intended to serve the public interest and the Council welcomes comments and suggestions on its reports or activities h m those interested in its work.

NCRP Publications NCFU? publications are distributed by the NCRP Publications' Office. Information on prices and how to order may be obtained by dimcting an inquiry to: NCFU?Publications 7910 Woodmont Avenue

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The currently available publications are listed below. NCRP Reports No.

Title

8 Control andRemoval of lbchmtive Contamination in Lobomtories (1951) 22 M k m u m Permissible Body Burdens and Mcrcimum Permissible Concentmtions of Radionuclides in Air and in Water for Occupational Eixposure (1959)Dncludea Addendum 1issued in August 19631 23 Measurement of Neutron Flux and &ctm for Physiwl and Biobgiwl App2icatwns (1960) 25 Measurement of Absorbed Dose of Neutrons, and of Mixtures of Neutrons and Gamma Rays (1961) 27 Stopping Powers for Use with Cavity Chambers (1961) 30 Safe Handling of Radioactive Materials (1964) 32 Radiation h t e c t i o n in Educational Institutions (1966) 35 Dentad X-Ray h t e c t i o n (1970) 36 hbckztion h t e c t i o n in Veterinary Medicine (1970) 37 A.eurutions in the Management of Patients Who Have Received Thempeutic Amounts of Radionuclides (1970) 38 h t e c t i o n Against Neutron Radiation (1971) 40 h t e c t w n A g h t hdiution from B m c h y t h e m Souroes (1972) 41 Specification of Gamma-h%zyBmchythempy Sources (1974)

72 1 NCRP PUBLICATIONS 42 Rddblogicul Factors Affecting Decision-M&ng in a NuclecwAttack (1974) 44 Krypton-85 in the Atmosphere-Accumulation, Biologicul Sign-, and Control Technology (1975) 46 Alpha-Emitting Particles in Lungs (1975) 47 TMHm Measurement Techniques (1976) 49 S t m t u m l Shielding Design and Evalwtion for Mediwl Use of X Rqys and Gamma Rqys of Energies Up to 10 MeV (1976) 50 Environmental Radiation Measurements (1976) 51 Radiation h t e c t i o n Design Guidelines for 0.1-100 MeV Particle Aceelemtor Facilities (1977) 52 Cesium-137fnom the Environment to Man; Metabolism and Dose (1977) 54 Mediwl Radiation Exposure of h g n o n t and Potentidy A-egnant Women (1977) 55 h t e c t i o n of the Thyroid Gland in the Event of Releases of Radioiodim (1977) 57 Instrumentation and Monitoring Methods for Radiation Protection (1978) 58 A Himdbook of Radioactwity Measurements h d u r e s , 2nd ed. (1985) 59 Opemtwnal Radiation Safety h g r a m (1978) 60 Physical, Chemioal, and BiologPioal Properties of l t i d t x e h m R e l e v m to Radiation h t e c t w n Guidelines (1978) 61 Radiation Safety lhining Criteria for I1Lstnhl Rdogmphy (1978) 62 TMium in the Environment (1979) Compounds 63 TMium and Other Radionuclide Labeled Or# Imrpomted in Genetic Material (1979) 64 Influence of h e and Its Distribution in If:mon Dose-Response Relationships for Low-LET Radiations (1980) 65 Management of Persons Accidentally Contaminated with Radionuclides (1980) ELectronugneticFields-Properties, @antitiescad 67 Radi~frequency Units, Biophysical Intemetwn, and Measurements (1981) 68 Radiation h t e c t w n in Pediatric Radiology (1981) 69 Dosimetry of X-Ray and GummaRay Beams for Rodwtion nLemlpy in the Energy Range 10 keV to 50 MeV (1981) 70 Ntlclear ~e&-~actors' Influencing the Choice and Use of Radionuclides in Dugnosis and nLemrpy (1982) 71 Operational Radiation Safety-%in&! (1983) 72 Radiation h t e c t i o n and Measurement for Low-Voltqge Neutron Genemtors (1983)

NCRP PUBLICATIONS / 73 73 h t e c t i o n in Nuclear Medicine and Ultmsound Diagmitic lhcecd~resin Children (1983) 74 l3iologica.l Effects of Ultmsound Mechanisms and Clinical Implkdwns (1983) 75 Iodine-129: Evaluation of Releases from Nuclear Power Genemtwn (1983) 76 Radiological Assessment: Bedicting the Transport, Biomcumulation, and Uptak.e by Man of Rhiionuclides Released to the Envhnment (1984) 77 Exposures from the U&m Series with Emphasis on Radon and Its Daughters (1984) 78 E m h i i o n of Occupational and Enuhnmental &posures to Radon and Radon Daughters in the United States (1984) 79 Neutron Contamincdionfrom Medioal Electron Accelemtors (1984) 80 Induction of Thyroid Cancer by Ionizing Radiation (1985) 81 Carbon-14 in the Environment (1985) 82 Sl Units in Radiation h t e c t i o n and Measurements (1985) 83 7R.eExperimental h i s for Absorbed-lhse CaZculatwnsin Medical Uses of Radionuclides (1985) 84 Geneml Concepts for the Dosimetry of I n t e d y Deposited Rizdionuclides (1985) 85 Mammography-A User$ Guide (1986) 86 Biol0gica.l Effects and Exposure Criteria for Radiofrequency Electromagnetic &Ms (1986) 87 Use of Bioassqy Procedures fir Assessment of I n t e d Radionuclide Deposition (1987) 88 Radiation Almms and Access Control Systems (1986) 89 Genetic Effectsfrom IntentalEy Deposited Radionuclides (1987) 90 Neptunium. Radicdion h t e c t i o n Guidelines (1988) 92 Public Radiation Exposure from Nuclear Power Genedion in the United States (1987) 93 Ionizing Radiation Erposure of the Population of the United States (1987) 94 Exposure of the Population in the United States and CanadQfrom Natuml Background Radiation (1987) 95 Radiation Exposure of the U.S Population from Consumer Products and MismUaneous Sources (1987) 96 Comparative Carcinogenicity ofIonizingRadiatwn and Chemicals (1989) 97 Measurement of Radon and Radon Daughters in Aw (1988)

74 / NCRP PUBLICATIONS 98 Guidance on Raaliation Received in &ace Activities (1989) 99 Quality Assumme for Dicrgnostic Imaging (1988) 100 Exposure of the U.S. Population from Diagnostic Medical Radiation (1989) 101 Exposure of the U.S. Population from Occupational Radiation (1989) 102 Medad X-Ray, Electron Beam and Gamma-Ray Protection for Energies Up to 50 MeV (Equipment Design, Performme and Use) (1989) 103 Control of Radon in Houses (1989) 104 lh Relative Biologiwl Effectiveness of Radiations of Different &uality (1ggC)) 105 RaaYation Protection for Me& and Allied Health Personnel (1989) 106 Limit for Exposure to "Hot Particlesr1on the hein (1989) 107 Implementation of the Ainnple of As Low As Reasonably Achievable ( A M ) for Medical and Dental Personnel (1990) 108 Conceptual Basis for Calculations of A b s o r b e d h Distributions (1991) 109 Effects of Ionizing Radiation on Aquatic Organism (1991) 110 Some Aspects of Strontium Ibdhbiology (1991) 111 Developing Radiation Emergency Plans for Academic, Medad or I&td Facilities (1991) 112 Calibmtion of Survey Instruments Used in Radiation Protection for the Assessment of Ionizing Radiation Fields and Radioactive Surf' Contamination (1991) 113 Exposure Criteria for Medical DLa;gnostic Ultmsourd I. Criteria Based on llhermal Mechanisms (1992) 114 Maintaining Radiation Protection Records (1992) 115 Risk Estimates for Radiation Protection (1993) 116 Limitation of Exposure to Ionizing Radiation (1993) 117 Research Needs for Radiation h t e c t i o n (1993)

Binders for NCRP reports are available. Two sizes make it possible to collect into small binders the "old aeries1' of reports (NCRP Reports Nos. 8-30)and into large binders the more recent publications (NCRP Reports Nos. 32-117).Each binder will accommodate h m five to seven reports. The binders cany the identikation I1NCRPReports1'and come with label holders which permit the user to attach labels showing the reports contained in each binder.

NCRPPUBLICATIONS / 75

The following bound sets of NCRP reports are also available: Volume I. Volume 11. Volume III. Volume IV. Volume V. Volume VI. Volume VII. Volume VIII. Volume E. Volume X Volume XI. Volume XII. Volume Xm. Volume XIV. Volume XV. Volume XVI. Volume XM. Volume XVIII. Volume XIX Volume XX Volume XXI. Volume XXII.

NCRP Reports Nos. 8,22 NCRP Reports Nos. 23, 25.27,30 NCRP Reports Nos. 32,35, 36,37 NCRP Reports Nos. 38,40,41 NCRP Reports Nos. 42,44, 46 NCRP Reports Nos. 47, 49, 50, 51 NCRP Reports Nos. 52,53,54,55,57 NCRP Report No. 58 NCRP Reports Nos. 59,60,61,62,63 NCRP Reports Nos. 64,65,66,67 NCRP Reports Nos. 68, 69, 70, 71, 72 NCRP Reports Nos. 73, 74, 75, 76 NCRP Reports Nos. 77, 78, 79, 80 NCRP Reports Nos. 81,82,83,84,85 NCRP Reports Nos. 86,87,88,89 NCRP Reports Nos. 90, 91,92, 93 NCRP Reports Nos. 94,95, 96,97 NCRP Reports Nos. 98,99,100 NCRP Reports Nos. 101, 102, 103, 104 NCRP Reports Nos. 105, 106, 107, 108 NCRP Reports Nos. 109, 110, 111 NCRP Reports Nos. 112, 113, 114

mtles of the individualreports contained in each volume are given above.)

NCRP Commentaries No.

Title

1 Krypton-85 in the Atmosphere-With Specific Referem to the Public H e d h Stgni,ficaace of the Proposed Controlled Release at Three Mile Island (1980) 2 Relimincay Evaluation of Criteria for the fiposal of lhmumnic Contaminated Waste (1982) 3 h e n i n g Techniques for Determining Compliance with Environmental Stamhds-Releases of Radionuclides to the Atmosphem (1986), Revised (1989) 4 Guidelines for the Release of Waste Water from Nuclear F&ies with Special Reference to the Public Health Sgni&ma of the

76 1 NCRP PUBLICATIONS

Proposed Release of l k a t e d Waste Waters at Thme Mile Island (1987) Review of the Publication, Living Without Lmd@s (1989) Radon Exposum of the U.S.Population-Status of the Problem (1991) Miaiiministmtion of Radioactive Material in Mediche-S&ntific Background (1991) Uncertainty in NCRP h e n i n g Models Relating to Atmospheric h p o r t , Deposition and Uptake by H u m (1993)

Proceedings of the Annual Meeting No.

Title

1 Perceptions of Risk, Proceedings of the F i b n t h Annual Meeting held on March 1415, 1979 (includmg Taylor lecture No. 3) (1980) CriticalIssues in Setting Radiation Dose Limits, Proceedingsof the Seventeenth Annual Meeting held on April 8-9,1981(including Taylor JA&UT? No. 5) (1982) Radiation Protection and New Medical Diagmstic A p p m h e s , b e d i n g a of the Eighteenth h u a l Meeting held on April 67,1982 (includingTaylor bcture No. 6) (1983) Environmental Radioactivy Proceedings of the Nineteenth Annual Meeting held on April 6-7,1983 (including Taylor Lecture No. 7) (1983) Some Issues Importmt in Developing Basic Radiation h t e c t i o n Recommendations, Proceedings of the Twentieth Annual Meeting held on April 4-5, 1984 (includingTaylor hcture No. 8) (1985) Radiaactwe Waste, Proceedings of the Twenty-&st Annual Meeting held on April 3-4, 1985 (including Taylor I&xm No. 9)(1986) Nonionizing Electromagnetic Radiations and Ultrasound, hmedhgs of the Twenty-secondAnnual Meeting held on April 2-3,1986 (includingTaylor Lectmn! No. 10) (1988) New Dosimetry at Hiroshima and N a g d i and Its Implications for Risk Estimates, Proceedings of the Twenty-third Annual Meeting held on April 8-9,1987 (including Taylor Lecture No. 11) (1988)

NCRP PUBLICATIONS /

77

10 Radon,Prnceedings of the Twenty-fourth Annual Meeting held on March 30-31,1988 (includingTaylor Lecture No. 12)(1989) 11 Radiotion Protection Te-27W NCRP at m y Yews, Proceedings of the Twenty-fdth Annual Meeting held on April 5-6,1989 (includingTaylor Lecture No. 13)(1990) 12 Health and Ecologid Implimtions of Radioactiveb Contaminated Environments, Proceedingsof the Twenty-sixthhual Meeting held on April 45,1990(includingTaylor k t u r e No. 14)(1991) 13 Genes, C m r and Radiatwn Protection, Proceedmga of the Twenty-seventh Annual Meeting held on April 3-4,1991 (includingTaylor Ledure No. 15)(1992) 14 Radiation Protection in Medicine,Proceedingsof the 'hentyeighth Annual Meeting held on April 1-2,1992 (including Taylor Lecture No. 16)(1993) Lauriston S. Taylor Lectures No.

Title

1 27W Sqwres of the Natuml Numbers in Radiation Protection by Herbert M. Parker (1977) 2 Why be Quantitative about Rrcdiation Risk Estimates? by Sir Edward Pochin (1978) 3 Radiation P r o t e c t i o d w p t s and Bwde Offs by Hymer L. Friedell (1979)[Available also in Perceptions of Risk, see above] 4 From "Qzumtity of R . i o n " and 'Zbse" to 'Exposureffond 'Xbsorbed Dose'LAn Historical Review by Harold 0.Wyckoff (1980) 5 How Well Can We Assess Genetic Risk? Not Vely by James F. Crow (1981) [Available also in Critical Issues in Setting IMiation Dose Limits, see above] 6 Ethics, M - o f f s and Media$ Radiation by Eugene L. Saenger (1982)[Available also in Radiation Protection and New Medical Dutgnostic A p p m h e s , see above] 7 27W Human Environment-Past, Present and m u r e by Menil Eisenbud (1983)[Available also in Environmental lhdhuctivity, see above] 8 Limitation and Assessment in Racliation Protection by Harald H. Roasi (1984) [Available also in Some Issues Important in Developing &sic Radicdion Protection Recommendations, see above]

78 / NCRP PUEIJCATIONS 9 ! h t h (and Beauty) in Radiation Measurement by John H.Harley (1985) [Available also in Radioactive Waste, see above] 10 &logical Effects of Non-ionizing Radications: Cellular Properties anol Intemctions by Herman P. Schwan (1987) [Available also in Nonionizing Electromagnetic Radiations anol Ultmsound, see above] 11 How to be &uantzhtive about Radiation Risk Estimates by Seymour Jablon (1988) [Available also in New-Dosimetry cd Hiroshima anol Nagasaki and its Implications for Risk Estimates, see above] 12 How Safe is Safe Enough? by Bo Lindell(1988) [Available also in Radon, see above] 13 Radiobiology and Radiation Fbtection: 7 7 Past ~ Century and Prospects for the Future by Arthur C. Upton (1989) [Available also in Radiation Protection Today, see above] 14 Radiation Protection anol the Internal Emitter Saga by J. Newel1 Stannard (1990) [Available also in Health and Ewlogiwl Implications of Raalioactively Gntaminated Environments, see above] 15 When is a Dose Not a h e ? by Victor P. Bond (1992) [Available also in Genes, C m r and Radiation htection, see above] 16 Dose and Risk in Diagnostic Radiology:How Big? How Little? by Edward W. Webster (1992) [Available also in Radiation Protection in Medicine, see above] 17 Science, Radiation Protection lmd the NCRPby Warren K. Sin* (1993) Symposium Proceedings !lhControl of Exposure of the fib& to Ionizing Radiation in the Event of Accident or Attack, Proceedings of a Symposium held Apd 27-29, 1981 (1982)

*

No.

NCRP Statements Title

1 " B b d Counts,Statement of the National Committee on Radiation Pmtection," Radiology 63, 428 (1954)

NCRP PUBLICATIONS / 79 2 "Statements on Maximum Permkible Dose from Television Receivers and Maximum Permissible Dose to the Skin of the Whole Body," Am. J. RoentgenoL, Radium Ther. and N u d Med. 84, 152 (1960) and Radiology 75, 122 (1960) 3 X-Rayh t e c t i o n St-& for Home TelevisionReceivers, Interim Statement of the Notional Council on Radiation FWection and Measurements (1968) 4 Specz@ation of Units of Nbtuml Umnium a d Naduml ITtorium, Statement of the Notional Council on m i o n Protection and Measurements, (1973) 5 NCRP Statement on Dose Limit for Neutrom (1980) 6 Control of Air Emissions of Raa!jonuclides (1984) 7 l7w Probability l7m.t a Particdm Maligmmy Mw Haue Been C a s e d by a &wcified I-ion (1992)

Other Documents The following documents of the NCRP we= published outside of the NCRP Report, Commentary and Statement aeries:

&matic lhdiution Dose for the Geneml Population, Report of the Ad Hoc Committee of the National Council on Radiation Protection and Measurements, 6 May 1959, Science, February 19, 1960, VoL 131, No. 3399, pages 482486 Dose Effect MocliJjting Factors In Raclicrtion Protection, Report of Su-ttee M-4 (Relative Biological Effectiveness) of the National Council on Radiation Protection and Measurements, Report BNL 50073 (7-471) (1967) Brookhaven National Laboratory (National Technical Information Service Sprhghld, Virginia) The following documents are now superaeded andlor out of print:

NCRP Reports No.

Title

1 X-Rcqy h t e c t i o n (1931) [superaeded by NCRP Report No. 31 2 Radium Protection (1934) [Superseded by NCRP Report No. 41

80 1 NCRP PUBLICATIONS 3 X-Rcy Protection (1936) [Superseded by NCRP Report NO. 61 4 Radium Protection (1938) [Superseded by NCRP Report No. 131 5 Safe H d i n g of Radioactive Luminous Compound (1941) [Out of Print] 6 Medioal X-Ray Protection Up to l'h Mdlion Volts (1949) [Superseded by NCRP Report No. 181 7 Safe Handling of hh'ioactive Isotopes (1949) [Superseded by NCRP Report No. 301 9 Rewmmendations for Waste Disposal of Phosphom-32 and I&-131 for Me& Users (1951) [Out of Print] 10 R&b@ Monilonjtg Methods and Instruments (1952) [Superseded by NCRP Report No. 571 11 Mmimum Permissible Amounts of Ridimkotopes in the H u m Body and M&um Permissible Concentmtions in Air cad Water (1953) [Superseded by NCRP Report No. 221 12 Recommendations for the Disposal of Carbon-14 Wastes (1953) [Superseded by NCRP Report No. 811 13 Protection Against Radiations from Radium, Cobalt-60 and Cesium-137 (1954) [Superseded by NCRP Report No. 241 14 Protection Against Betatron-Synchrotron Radiations Up to 100 MiUion Electron Volts (1954) [Supersededby NCRP Report No. 511 15 safe Handling of Cadavers Containing h!achactwe Isotopes (1953) [Superseded by NCRP Report No. 211 16 Rimkctwe- Waste Disposal in the Ocean (1954) [Out of Print] 17 Permissible Dose from Extental Sources of Ionizing Radiation (1954) including Mmimum Permissible Exposures to Man, Addendum to N a t i o d Bureau of St-& Hadbook 59 (1958) [Superseded by NCRP Report No. 391 18 X-Ray Protection (1955) [Superseded by NCRP Report No. 261 19 Regukdion of Radiation Exposure by Legiskdive Means (1955) [Out of Print] 20 Protection Against Neutron RacEiation Up to 30 Miilion Electron Volts (1957) [Superseded by NCRP Report No. 381 21 safe H d i n g of Bodies Containing h!achactive Isotopes (1958) [Superseded by NCRP Report No. 371 24 Protection Against Radiations from Sealed Gamma Sources (1960) [Superseded by NCRP Reports No. 33,34 and 401 26 Medical X-Ray Protection Up to Zhree Million Volts (1961) [Superseded by NCRP Reports No. 33,34,35 and 361

NCRPPUBLICATIONS / 81 28 A M m d of Rkdiaactivity Proceckres (1961) [Superseded by NCRP Report No. 581 29 Exposure to l?ud&ion in m Emergency (1962) puperseded by NCRP Report No. 421 31 Shieldingfor High-Energy ElectronAcoelenrdor Instauations (1964) [Superseded by NCRP Report No. 511 X-Ray caul G a m m R a y Rvtection for Energies up to 10 33 Me& MeV-Equipment Design and Use (1968) [Supersededby NCRP Report No. 1021 34 Mediwl X-Ray and Gmmu-Ray h t e c t i o n for Energies Up to 10 MeV--Stncctuml &lding Design and Evaluation Handbook (1970) [Superseded by NCRP Report No. 491 39 &sic Radiation h t e c t i o n Criteria (1971) puperaeded by NCRP Report No. 911 43 Review of the Current State of Radiation h t e c t i o n Philosophy (1975) [Superseded by NCRP Report No. 911 45 Natuml Background Radiation in the United States (1975) [Superseded by NCRP Report No. 941 48 Radiation h t e c t i o n for Medical cmd Allied Health Personnel (1976) [Superseded by NCRP Report No. 1051 53 Review of NCRP Radiation Dose Limit for Embryo and Fetus in Ocmpatiody-Exposed Women (1977) [Out of Print] 56 RQdiation Exposure from Consumer Aoducts and MisceUaneous Sourns (1977) [Superseded by NCRP Report No. 9-51 58 A Hof Rachactivity Measmments Procedures, 1st ed. (1978) [Superseded by NCRP Report No. 58.2nd ed.] 66 Mammgmphy (1980) [Out of Print] 91 Rewmrnendations on L i m b for Exposm to Ionizing Radiation (1987) [Supeded by NCRP Report No. 1161

NCRP Proceedings No.

Title

2 Qumtitative Risk in tS Setting, Proceedings of the SixteenthAnnual Meeting held on April 2-3.1980 [Out of Print]

Index Absolute riak model 33 Acute radiation exp&ure, 3 Aneuploidy, 14 Annual re&rence lev& of intake. 25 Atomic-bomb s u v i m , 34 irradiated in utem, 34 Biokhetic models, 19 Biologic dosimeters, 10,11 Biologic ei%cta, 39 radiation in space, 39 Biologic markers, 11 chromosome aberrations, 11 Calculational models, 21,22 external radiation fielda, 22 Cancer and developmental riaks, 15 in-utem exposure, 15 Cmcinogenesis, 11,31,33,42 mathematical models of, 11 mechanisms of, 11 radiation-related, 31 risk assessment, 42 temporal expression, 33 Cellular and molecular changes, 4 exposures to radiation, drugs and chemicals, 4 Cellular responses, 8 modulation, 8 Chromosome aberrations, 11 biologic dosimeter, 11 Collective dose, 46 Complex cahdationalmodela, 25 experimental vefication, 25 Design of M t i e s , 47 optimizing, 47 Deterministic eefFecta, 3 Distribution of energy absorbed, 23

Auger-electron emitter 12%, 23 low-energy beta emitter 23 DNA alterations, 12 DNA repair deficiencies, 6 ataxia telangiectasia, 6 Bloom's syndrome, 6 Chkayne's syndrome, 6 Fanmni's anemia, 6 xeroderma pigmentosum, 6 DNA repair enzymes, 7 induction of, 7 Dose assessment models, 23 environmental parameters, 23 Dose determination, 17,24 epidemiologic studies, 17 Japanese auvivors, 17 transport parameters, 24 Dose-rate efFeetiveness fador, 30 Dose-response relatiomhips, 30,35 internally depoeited radionuclides, 35 life-span studies, 35 Dose to bronchial tissues from radon progeny, 27 Doses to the population, 46 Dosimetric techniques, 25 Dosimetzy models, 21

EfFective dose, 20 Environmental monitoring, 26 Epidemiologic methods, 40 Epidemiologic studies, 32 low-LETexpoeures, 32 Estimates of riak, 38 1311, 38 Exposure analysis, 17 Exposure and risk, 50 Exposure to radiation, drugs and chemicals, 4 cellular and molecular changes, 4

INDEX / 83 External radiation fields, 22 calculational models, 22 Extrapolation of risk, 15

Galactic cosmic rays, 47 Gene expression, 8 associated with activation and induction, 8 associated with mutational lose, 8 Genetic alterations, 8, 12, 10, 14 in germ cells, l2 persistence of radiation-induced, 8 radiation induced, 8, 14 reproductive tissues, 14 transhrmed ceb, 10 Genetic diseases, 14, 15 dose-response relationehipa, 15 genetic equilibrium, 14 m d f i d o r i a l diseases, 14 Genetic efFems, 12 estimates of, 12 in germ cells, 12 mdfidorial genetic diseases, 12 mutation doubling dose, l2 Genetic equilibrium, 14 Genetic risk, 13, 15 heritable, 13 impact of mulfictorial diseases, 15 Genetic variability, 5 risk of radiation induced cancer, 5 Host susceptibiity hctma, 41,42 age a t exposure, 42 RZE particles, 48 Immune system, 42 In-situ hybridization, 3

Internal emitters, 2 1 calculational models, 21 Internally deposited radionuclides, 18,30, 36 Intervention, 45 Intervention in radiation carcinogenesie, 9 In-utem exposm, 15,34

In-vitm studies, 10, 11 alterations in cell pmlil%ration, 11 biologic dosimeters, 10 chrommme translocation, 11 fluorescence in-situ hybridization, 10 other kaqmtypic alterations, 11 polymer- chain reaction, 10 Irradiation in utem, 15 Leukemia, 43 preconception irradiation, 43 Leukemia risk in offipring, 31 I&-span studies, 35 doee-response r e l a t i o ~ h i p35 , Li6etime radiation risks, 33 absolute risk model, 33 relative risk model 33 h-dose-rate exposure, 3 molecular effects, 3 risks of, 3 Mathematical models, 11,41 Medical radiation sources, 46 risksof,46 Mental retardation risks, 16 Metabolic models, 18 age and health-dated variations, 18 hr internally deposited radionudides, 18 Models of carcinogenesis, 9 Molecular changes, acute, 3 Molecular effects, 3 acute radiation expoam, 3 low-doee-rate expasure, 3 Molecular markers, 5 carcinogenesis in the respiratory trad, 5 Mutation doubling dose,l2 Mutation risks, 4 National radiation dose registry, 35 Neoplastic tamdmmtion, 4 Neutron doses, 40

84 / INDEX Nuclear accident, 49 Occupational radiation expc~~ures, 47 Patient d m , 46 dhgmstk outcome, 45 radio* image quality,45 Percept;on, 45 Perception and public p o h , 49 Perception of risk, 50 Physiologic modela, 18 age and health-related variations, 18

fir i n t e d y deposited radionuclides, 18 Polymerase chain reaction, 3 hvention, 45 molecular and cellular techniques, 45 Radiation and other riske, 51 asaesement of societal values, 61 Radiation epidemioaogY, 32 Radiation h l d quantities,27 Radiation in apace, 39 biologic efkxb, 39 Radiation protection, 18 age and health-related ~ariatio118, 18

tbr interm& deposited radionuclidee, 18 Radiation protection stan-, 4 Radiation-related carcinogeneeis, 3 1 Radiation response, 9 Radiation risk, 42, 49 public perceptio~m,49 Radiation ahieldmg, 47 Radiation tramport, 21 calculational models, 21 Radiation workers, 35 national dose registry, 35 Radiocarbon, 24 Radiologic accidents, 48 muntermeaawtxi b m Radionuclides, 50 riek fhctom, 50 Radon exposure, 36,38

,48

estimatea of risk, 36 residential, 38 Relative biological e&&imnea

WE), 5,30,39 neutrons, 39 Relative risk model, 33 Resouroe requirements, 53 Respiratory tract, 5 molecular markers, 6 Risk, 16, 60, 62 common expressions, 50 level of aazptability, 62 mental retardation, 16 Risk assessment, 29,35,42 animals studies, 29 carcinogenesis, 42 cell survival, 42 high-LEI' particlea, 35 intemal radionuclides, 36 neutron exposures, 29 Risk estimates, 34 trans& across p o p u l a ~ ,34 Risk factors, 60 Risks~mexposuretalowdoeeand hctionated or prokacted low-LET irradiation, 33 Risk of radiation, 23 microscopic energy distribution, 23 submicmsmpicenergy distribution, 23

Risk of radiation-induced cancer, 5, 6

DNA repair dekiencies, 6 genetic variability, 5 heterozygvus carriers, 6 molecular markers, 6

Screening models for environmental contnminnnh, 28 Shielding, 47 Technetium, 24 tmnqmrt parameters, 24 Tiseue weighing factma, 21

Uranium uptake, 26