NCRP Report No 136 Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation Recommendations of the NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS Issued June 4, 2001 National Council on Radiation Protection and Measurements 7910 Woodmont Avenue, Suite 800 / Bethesda, Maryland 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 documents 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 infringe 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 as amended 42 U.S.C Section 2000e et seq (Title VII) or any other statutory or common law theory governing liability Library of Congress Cataloging-in-Publication Data Evaluation of the linear-nonthreshold dose-response model for ionizing radiation p cm — (NCRP report ; no 136) ‘‘June 2001.’’ Includes bibliographical references and index ISBN 0-929600-69-X Radiation—Toxicology Low-level radiation—Dose-response relationship I National Council on Radiation Protection and Measurements Scientific Committee 1-6 on Linearity of Dose Response II Series RA1231.R2 E935 2001 612Ј.01448—dc21 2001032614 Copyright © National Council on Radiation Protection and Measurements 2001 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 [For detailed information on the availability of NCRP publications see page 273.] Preface In developing its basic radiation protection recommendations, as given in NCRP Report No 116, Limitation of Exposure to Ionizing Radiation (NCRP, 1993a), the Council reiterated its acceptance of the linear-nonthreshold hypothesis for the risk-dose relationship Specifically, ‘‘based on the hypothesis that genetic effects and some cancers may result from damage to a single cell, the Council assumes that, for radiation-protection purposes, the risk of stochastic effects is proportional to dose without threshold, throughout the range of dose and dose rates of importance in routine radiation protection Furthermore, the probability of response (risk) is assumed, for radiation protection purposes, to accumulate linearly with dose At higher doses received acutely, such as in accidents, more complex (nonlinear) dose-risk relationships may apply.’’ This Report is the result of an in-depth review by NCRP Scientific Committee 1-6 of the scientific basis for this assumption, i.e., the relationship between dose and risk at low doses Scientific Committee 1-6 sought and obtained written and oral input from several scientists in the United States who held many different views regarding the science associated with this subject and I want to thank those scientists for their frank and candid input to the Committee’s work Since this Committee was constituted to address the scientific issues, the implications of the Committee’s work for radiation protection policy will be addressed by NCRP at a later point in time Serving on NCRP Scientific Committee 1-6 on Linearity of Dose Response were: Arthur C Upton, Chairman University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School New Brunswick, New Jersey Members S James Adelstein Harvard Medical School Boston, Massachusetts Eric J Hall Columbia University New York, New York iii iv / PREFACE David J Brenner Columbia University New York, New York Howard L Liber Massachusetts General Hospital Boston, Massachusetts Kelly H Clifton University of Wisconsin Madison, Wisconsin Robert B Painter University of California San Francisco, California Stuart C Finch University of Medicine and Dentistry of New Jersey Camden, New Jersey R Julian Preston U.S Environmental Protection Agency Research Triangle Park, North Carolina Roy E Shore New York University Medical Center New York, New York Advisor Amy Kronenberg Lawrence Berkeley National Laboratory Berkeley, California NCRP Secretariat W Roger Ney, Consultant (1999–2001) Eric E Kearsley, Staff Scientist (1997–1998) William M Beckner, Senior Staff Scientist (1995–1997) Cindy L O’Brien, Managing Editor The Council wishes to express its appreciation to the Committee members for the time and effort devoted to the preparation of this Report and to the U.S Nuclear Regulatory Commission for its financial support of this activity Charles B Meinhold President Contents Preface Executive Summary Introduction Biophysical 3.1 Energy Deposition and Its Relevance to Questions of Low-Dose Response 3.1.1 Track Structure 3.1.2 Quantitative Characterization of Energy Deposition in Small Sites 3.1.3 Definition of Low Dose, Corresponding to an Average of One Energy Deposition Event per Target 3.2 Implications of Energy-Deposition Patterns for Independent Cellular Effects at Low Doses 3.3 Implications of Energy-Deposition Patterns for Carcinogenic Effects of Radiation 3.3.1 Evidence Regarding the Clonality of Tumors 3.3.2 Relationship Between Initially-Damaged Cells and Tumorigenic Cells 3.4 Conclusions 3.5 Research Needs Deoxyribonucleic Acid Repair and Processing after Low Doses and Low-Dose Rates of Ionizing Radiation 4.1 Ionizing Radiation-Induced Deoxyribonucleic Acid Lesions and Their Repair 4.1.1 Single-Strand Breaks (Including Deoxyribose Damage) 4.1.2 Base Damage and Loss 4.1.3 Deoxyribonucleic Acid-Protein Cross-Links 4.1.4 Double-Strand Breaks 4.1.5 Multiply-Damaged Sites 4.1.6 Mismatch Repair 4.1.7 Effects of Linear-Energy Transfer 4.1.8 Spontaneous Deoxyribonucleic Acid Damage 4.2 Cell-Cycle Checkpoints 4.3 Programmed Cell Death (Apoptosis) v iii 11 11 11 14 16 18 20 21 22 23 24 25 25 25 27 28 28 29 30 30 30 31 32 vi / CONTENTS 4.4 Impact of Cell-Cycle Checkpoints and Apoptosis on the Dose Response for Deoxyribonucleic Acid Repair at Low-Dose Rates 4.5 The Adaptive Response 4.6 Summary 4.7 Research Needs Mutagenesis 5.1 Introduction 5.2 Potential Mechanisms of Mutagenesis 5.2.1 Replication Errors 5.2.2 Mutations Arising During Repair 5.3 Dose-Response Studies with Low Linear-Energy Transfer Radiation 5.3.1 Human in Vivo 5.3.2 Animal in Vivo 5.3.3 Mammalian Cells in Vitro 5.3.3.1 Assays at the Hypoxanthine Phosphioribosyl Traniferase Locus 5.3.3.2 Assays at Other Genetic Loci 5.3.3.3 Dose-Rate Effects 5.3.3.4 Effect of Genetic Background 5.3.3.5 Inducible Systems 5.3.3.5.1 Genomic instability 5.3.3.5.2 Adaptive response 5.4 Dose-Response Studies with High Linear-Energy Transfer Radiation 5.5 Summary 5.6 Research Needs Chromosome Aberrations Induced by Low Doses and Low-Dose Rates of Ionizing Radiation 6.1 Misrepair, Misreplication, and Chromosome Aberration Formation 6.1.1 Chromosome-Type Aberrations 6.1.2 Chromatid-Type Aberrations 6.1.3 Mechanisms of Formation of Chromosome Aberrations 6.1.3.1 Low Linear-Energy Transfer Radiations 6.1.3.2 High Linear-Energy Transfer Radiations 6.1.4 Dose-Response Curves: Acute and Chronic Exposures 32 33 34 34 36 36 36 36 37 37 37 39 41 41 42 44 45 45 45 46 46 48 49 50 50 51 51 52 53 55 55 CONTENTS 6.2 6.3 6.4 6.5 6.6 6.7 / 6.1.4.1 Low Linear-Energy Transfer Radiations 6.1.4.2 High Linear-Energy Transfer Radiations Distribution of Aberrations Within and Among Cells 6.2.1 Intercellular Distributions of Chromosome Aberrations 6.2.2 Inter- and Intrachromosomal Distribution of Chromosome Aberrations Uncertainties in Shapes of Dose-Response Curves at Low Doses 6.3.1 Nonlinear and Threshold Responses 6.3.2 Effect of Adaptive Response 6.3.3 Efficiency of Deoxyribonucleic Acid Repair 6.3.4 Inducibility of Deoxyribonucleic Acid Repair and Cell-Cycle Checkpoints 6.3.5 Genomic Instability Association Between Chromosomal Changes and Cancer Biological Dosimetry for Chromosome Aberrations 6.5.1 Acute Exposures 6.5.2 Chronic Exposures 6.5.3 Evidence for Threshold and/or Linearity in Dose Response 6.5.4 Implications for Dose Response for Carcinogenic Effects Summary and Conclusions Research Needs Oncogenic Transformation in Vitro and Genomic Instability 7.1 Dose-Response Relationships 7.2 Shape of the Dose-Response Relationship for Oncogenic Transformation 7.3 The Bystander Effect 7.4 Transformation by High Linear-Energy Transfer Radiations 7.5 The Dose-Rate Effect 7.6 Modulation 7.7 Genomic Instability 7.8 Adaptive Response 7.9 Summary 7.10 Research Needs vii 55 56 56 57 57 59 59 61 62 62 63 71 74 74 76 77 77 78 79 81 81 83 89 91 91 92 94 95 96 97 viii / CONTENTS Carcinogenic Effects in Laboratory Animals 8.1 Introduction 8.2 Characteristics and Multistage Nature of Carcinogenesis in Model Systems 8.3 Dose-Response Relationships (Dose, Dose Rate, Linear-Energy Transfer) as Influenced by Homeostatic and Other Modifying Factors 8.3.1 Background 8.3.2 Leukemia 8.3.2.1 Thymic Lymphoma 8.3.2.2 Myeloid Leukemia 8.3.3 Osteosarcoma 8.3.4 Mammary Gland Tumors 8.3.5 Thyroid Neoplasia 8.3.6 Lung Tumors 8.3.7 Renal Neoplasms 8.3.8 Skin Tumors 8.3.9 Mouse Harderian Gland Tumors 8.4 Life Shortening 8.5 Summary 8.6 Research Needs Carcinogenic Effects in Human Populations— Epidemiological Data 9.1 Considerations in Using Epidemiologic Data for Low-Dose Risk Assessment 9.2 Types of Epidemiological Studies and Their Strengths and Weaknesses 9.2.1 Cluster Studies 9.2.2 Ecologic Studies (Studies of Aggregated Epidemiologic Data) 9.2.3 Case-Control Studies 9.2.4 Cohort Studies 9.3 Examination of Linearity of Dose Responses and Low-Dose Risks in Epidemiologic Data 9.3.1 Total Solid Cancers 9.3.2 Leukemia 9.3.3 Thyroid Cancer 9.3.4 Breast Cancer 9.3.5 Lung Cancer 9.3.5.1 Low Linear-Energy Transfer Irradiation 99 99 99 101 101 102 102 103 106 108 114 116 116 118 122 123 125 130 131 131 133 133 134 136 137 138 138 146 155 162 166 166 CONTENTS / 9.3.5.2 High Linear-Energy Transfer Irradiation 9.3.6 In Utero Irradiation 9.3.7 Impact of Modifying Factors on the Shape of the Dose-Response Curve 9.3.7.1 Host Susceptibility and Radiation Sensitivity to Cancer: Theory 9.3.7.2 Host Susceptibility and Radiation Sensitivity to Cancer: Current Information 9.3.7.3 Interactions between Radiation and Other Cancer Risk Factors or Exposures 9.3.8 Status of the Dose-Response Relationship in Epidemiologic Data 9.3.8.1 Hormesis 9.3.8.2 Linearity and Dose Thresholds 9.4 Summary 9.5 Research Needs ix 171 178 191 191 192 194 195 195 196 197 200 10 Adaptive Responses 202 10.1 Types of Adaptive Responses and Their DoseResponse Relationships 202 10.2 Implications for the Linear-Nonthreshold Model 205 11 Research Needs 206 12 Discussion and Conclusions 208 References 212 The NCRP 264 NCRP Publications 273 Index 283 Executive Summary This Report presents an evaluation of the existing data on the dose-response relationships and current understanding of the health effects of low doses of ionizing radiation.1 This reevaluation was carried out by Scientific Committee 1-6 of the National Council on Radiation Protection and Measurements (NCRP), which was charged to reassess the weight of scientific evidence for and against the linearnonthreshold dose-response model, without reference to associated policy implications The evaluation was prompted by the need to reassess the common use, for radiation protection purposes, of the linear-nonthreshold dose-response hypothesis in the light of new experimental and epidemiological findings, including growing evidence of adaptive responses to small doses of radiation which may enhance the capacity of cells to withstand the effects of further radiation exposure, and new evidence concerning the possible nature of neoplastic initiation The evaluation focuses on the mutagenic, clastogenic (chromosome-damaging), and carcinogenic effects of radiation, since these effects are generally postulated to be stochastic and to increase in frequency as linear-nonthreshold functions of radiation dose.2 For each type of effect, the relevant theoretical, experimental and epidemiological data are considered Furthermore, in an effort to avoid overlooking pertinent data in the evaluation, input was obtained from authorities in the field and from the scientific community at large The evaluation begins by considering the way in which radiation energy is deposited within cells and its implications for dose-response relationships As is customary, the amount of radiation producing an effect is conveniently specified as the energy absorbed per unit mass in the irradiated system; i.e., the dose (D) At the outset, it is noted that virtually all existing experimental and epidemiological data on the effects of sparsely ionizing [i.e., low linear-energy transfer (LET)] radiation come from observations at doses far above those in In this Report, the word ‘‘dose’’ is frequently used in its generic sense Publication 26 of the ICRP (1977) was the first to describe in detail that ‘‘stochastic’’ effects are those for which the probability of an effect occurring, rather than its severity, is regarded as a function of dose without a threshold NCRP Publications Information on NCRP publications may be obtained from the NCRP website (http://www.ncrp.com), e-mail (ncrppubs@ncrp.com), by telephone (800-229-2652), or fax (301-907-8768) The address is: NCRP Publications 7910 Woodmont Avenue Suite 800 Bethesda, MD 20814-3095 Abstracts of NCRP reports published since 1980, abstracts of all NCRP commentaries, and the text of all NCRP statements are available at the NCRP website Currently available publications are listed below NCRP Reports No 22 25 27 30 32 35 36 37 38 40 41 42 Title Control and Removal of Radioactive Contamination in Laboratories (1951) Maximum Permissible Body Burdens and Maximum Permissible Concentrations of Radionuclides in Air and in Water for Occupational Exposure (1959) [Includes Addendum issued in August 1963] Measurement of Absorbed Dose of Neutrons, and of Mixtures of Neutrons and Gamma Rays (1961) Stopping Powers for Use with Cavity Chambers (1961) Safe Handling of Radioactive Materials (1964) Radiation Protection in Educational Institutions (1966) Dental X-Ray Protection (1970) Radiation Protection in Veterinary Medicine (1970) Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides (1970) Protection Against Neutron Radiation (1971) Protection Against Radiation from Brachytherapy Sources (1972) Specification of Gamma-Ray Brachytherapy Sources (1974) Radiological Factors Affecting Decision-Making in a Nuclear Attack (1974) 273 274 44 46 47 49 50 51 52 54 55 57 58 59 60 61 62 63 64 65 67 68 69 70 72 73 74 75 / NCRP PUBLICATIONS Krypton-85 in the Atmosphere—Accumulation, Biological Significance, and Control Technology (1975) Alpha-Emitting Particles in Lungs (1975) Tritium Measurement Techniques (1976) Structural Shielding Design and Evaluation for Medical Use of X Rays and Gamma Rays of Energies Up to 10 MeV (1976) Environmental Radiation Measurements (1976) Radiation Protection Design Guidelines for 0.1 - 10 MeV Particle Accelerator Facilities (1977) Cesium-137 from the Environment to Man: Metabolism and Dose (1977) Medical Radiation Exposure of Pregnant and Potentially Pregnant Women (1977) Protection of the Thyroid Gland in the Event of Releases of Radioiodine (1977) Instrumentation and Monitoring Methods for Radiation Protection (1978) A Handbook of Radioactivity Measurements Procedures, 2nd ed (1985) Operational Radiation Safety Program (1978) Physical, Chemical, and Biological Properties of Radiocerium Relevant to Radiation Protection Guidelines (1978) Radiation Safety Training Criteria for Industrial Radiography (1978) Tritium in the Environment (1979) Tritium and Other Radionuclide Labeled Organic Compounds Incorporated in Genetic Material (1979) Influence of Dose and Its Distribution in Time on Dose-Response Relationships for Low-LET Radiations (1980) Management of Persons Accidentally Contaminated with Radionuclides (1980) Radiofrequency Electromagnetic Fields—Properties, Quantities and Units, Biophysical Interaction, and Measurements (1981) Radiation Protection in Pediatric Radiology (1981) Dosimetry of X-Ray and Gamma-Ray Beams for Radiation Therapy in the Energy Range 10 keV to 50 MeV (1981) Nuclear Medicine—Factors Influencing the Choice and Use of Radionuclides in Diagnosis and Therapy (1982) Radiation Protection and Measurement for Low-Voltage Neutron Generators (1983) Protection in Nuclear Medicine and Ultrasound Diagnostic Procedures in Children (1983) Biological Effects of Ultrasound: Mechanisms and Clinical Implications (1983) Iodine-129: Evaluation of Releases from Nuclear Power Generation (1983) NCRP PUBLICATIONS 77 78 79 80 81 82 83 84 85 86 87 88 89 90 92 93 94 95 96 97 99 100 101 102 103 104 105 106 107 / 275 Exposures from the Uranium Series with Emphasis on Radon and Its Daughters (1984) Evaluation of Occupational and Environmental Exposures to Radon and Radon Daughters in the United States (1984) Neutron Contamination from Medical Electron Accelerators (1984) Induction of Thyroid Cancer by Ionizing Radiation (1985) Carbon-14 in the Environment (1985) SI Units in Radiation Protection and Measurements (1985) The Experimental Basis for Absorbed-Dose Calculations in Medical Uses of Radionuclides (1985) General Concepts for the Dosimetry of Internally Deposited Radionuclides (1985) Mammography—A User’s Guide (1986) Biological Effects and Exposure Criteria for Radiofrequency Electromagnetic Fields (1986) Use of Bioassay Procedures for Assessment of Internal Radionuclide Deposition (1987) Radiation Alarms and Access Control Systems (1986) Genetic Effects from Internally Deposited Radionuclides (1987) Neptunium: Radiation Protection Guidelines (1988) Public Radiation Exposure from Nuclear Power Generation in the United States (1987) Ionizing Radiation Exposure of the Population of the United States (1987) Exposure of the Population in the United States and Canada from Natural Background Radiation (1987) Radiation Exposure of the U.S Population from Consumer Products and Miscellaneous Sources (1987) Comparative Carcinogenicity of Ionizing Radiation and Chemicals (1989) Measurement of Radon and Radon Daughters in Air (1988) Quality Assurance for Diagnostic Imaging (1988) Exposure of the U.S Population from Diagnostic Medical Radiation (1989) Exposure of the U.S Population from Occupational Radiation (1989) Medical X-Ray, Electron Beam and Gamma-Ray Protection for Energies Up to 50 MeV (Equipment Design, Performance and Use) (1989) Control of Radon in Houses (1989) The Relative Biological Effectiveness of Radiations of Different Quality (1990) Radiation Protection for Medical and Allied Health Personnel (1989) Limit for Exposure to ‘‘Hot Particles’’ on the Skin (1989) Implementation of the Principle of As Low As Reasonably Achievable (ALARA) for Medical and Dental Personnel (1990) 276 / NCRP PUBLICATIONS 108 Conceptual Basis for Calculations of Absorbed-Dose Distributions (1991) 109 Effects of Ionizing Radiation on Aquatic Organisms (1991) 110 Some Aspects of Strontium Radiobiology (1991) 111 Developing Radiation Emergency Plans for Academic, Medical or Industrial Facilities (1991) 112 Calibration of Survey Instruments Used in Radiation Protection for the Assessment of Ionizing Radiation Fields and Radioactive Surface Contamination (1991) 113 Exposure Criteria for Medical Diagnostic Ultrasound: I Criteria Based on Thermal 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 Protection (1993) 118 Radiation Protection in the Mineral Extraction Industry (1993) 119 A Practical Guide to the Determination of Human Exposure to Radiofrequency Fields (1993) 120 Dose Control at Nuclear Power Plants (1994) 121 Principles and Application of Collective Dose in Radiation Protection (1995) 122 Use of Personal Monitors to Estimate Effective Dose Equivalent and Effective Dose to Workers for External Exposure to LowLET Radiation (1995) 123 Screening Models for Releases of Radionuclides to Atmosphere, Surface Water, and Ground (1996) 124 Sources and Magnitude of Occupational and Public Exposures from Nuclear Medicine Procedures (1996) 125 Deposition, Retention and Dosimetry of Inhaled Radioactive Substances (1997) 126 Uncertainties in Fatal Cancer Risk Estimates Used in Radiation Protection (1997) 127 Operational Radiation Safety Program (1998) 128 Radionuclide Exposure of the Embryo/Fetus (1998) 129 Recommended Screening Limits for Contaminated Surface Soil and Review of Factors Relevant to Site-Specific Studies (1999) 130 Biological Effects and Exposure Limits for ‘‘Hot Particles’’ (1999) 131 Scientific Basis for Evaluating the Risks to Populations from Space Applications of Plutonium (2001) 132 Radiation Protection Guidance for Activities in Low-Earth Orbit (2000) 133 Radiation Protection for Procedures Performed Outside the Radiology Department (2000) 134 Operational Radiation Safety Training (2000) 135 Liver Cancer Risk from Internally-Deposited Radionuclides (2001) 136 Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation (2001) Binders for NCRP reports are available Two sizes make it possible to collect into small binders the ‘‘old series’’ of reports (NCRP Reports Nos 8-30) and into large binders the more recent publications (NCRP Reports NCRP PUBLICATIONS / 277 Nos 32-136) Each binder will accommodate from five to seven reports The binders carry the identification ‘‘NCRP Reports’’ and come with label holders which permit the user to attach labels showing the reports contained in each binder The following bound sets of NCRP reports are also available: Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume I NCRP Reports Nos 8, 22 II NCRP Reports Nos 23, 25, 27, 30 III NCRP Reports Nos 32, 35, 36, 37 IV NCRP Reports Nos 38, 40, 41 V NCRP Reports Nos 42, 44, 46 VI NCRP Reports Nos 47, 49, 50, 51 VII NCRP Reports Nos 52, 53, 54, 55, 57 VIII NCRP Report No 58 IX NCRP Reports Nos 59, 60, 61, 62, 63 X NCRP Reports Nos 64, 65, 66, 67 XI NCRP Reports Nos 68, 69, 70, 71, 72 XII NCRP Reports Nos 73, 74, 75, 76 XIII NCRP Reports Nos 77, 78, 79, 80 XIV NCRP Reports Nos 81, 82, 83, 84, 85 XV NCRP Reports Nos 86, 87, 88, 89 XVI NCRP Reports Nos 90, 91, 92, 93 XVII NCRP Reports Nos 94, 95, 96, 97 XVIII NCRP Reports Nos 98, 99, 100 XIX NCRP Reports Nos 101, 102, 103, 104 XX NCRP Reports Nos 105, 106, 107, 108 XXI NCRP Reports Nos 109, 110, 111 XXII NCRP Reports Nos 112, 113, 114 XXIII NCRP Reports Nos 115, 116, 117, 118 XXIV NCRP Reports Nos 119, 120, 121, 122 XXV NCRP Report No 123I and 123II XXVI NCRP Reports Nos 124, 125, 126, 127 XXVII NCRP Reports Nos 128, 129, 130 (Titles of the individual reports contained in each volume are given above.) NCRP Commentaries No Title Krypton-85 in the Atmosphere—With Specific Reference to the Public Health Significance of the Proposed Controlled Release at Three Mile Island (1980) Guidelines for the Release of Waste Water from Nuclear Facilities with Special Reference to the Public Health 278 / 10 11 12 13 14 15 NCRP PUBLICATIONS Significance of the Proposed Release of Treated Waste Waters at Three Mile Island (1987) Review of the Publication, Living Without Landfills (1989) Radon Exposure of the U.S Population—Status of the Problem (1991) Misadministration of Radioactive Material in Medicine— Scientific Background (1991) Uncertainty in NCRP Screening Models Relating to Atmospheric Transport, Deposition and Uptake by Humans (1993) Considerations Regarding the Unintended Radiation Exposure of the Embryo, Fetus or Nursing Child (1994) Advising the Public about Radiation Emergencies: A Document for Public Comment (1994) Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients (1995) Radiation Exposure and High-Altitude Flight (1995) An Introduction to Efficacy in Diagnostic Radiology and Nuclear Medicine (Justification of Medical Radiation Exposure) (1995) A Guide for Uncertainty Analysis in Dose and Risk Assessments Related to Environmental Contamination (1996) Evaluating the Reliability of Biokinetic and Dosimetric Models and Parameters Used to Assess Individual Doses for Risk Assessment Purposes (1998) Proceedings of the Annual Meeting No Title Perceptions of Risk, Proceedings of the Fifteenth Annual Meeting held on March 14-15, 1979 (including Taylor Lecture No 3) (1980) Critical Issues in Setting Radiation Dose Limits, Proceedings of the Seventeenth Annual Meeting held on April 8-9, 1981 (including Taylor Lecture No 5) (1982) Radiation Protection and New Medical Diagnostic Approaches, Proceedings of the Eighteenth Annual Meeting held on April 6-7, 1982 (including Taylor Lecture No 6) (1983) Environmental Radioactivity, Proceedings of the Nineteenth Annual Meeting held on April 6-7, 1983 (including Taylor Lecture No 7) (1983) Some Issues Important in Developing Basic Radiation Protection Recommendations, Proceedings of the Twentieth Annual Meeting held on April 4-5, 1984 (including Taylor Lecture No 8) (1985) Radioactive Waste, Proceedings of the Twenty-first Annual Meeting held on April 3-4, 1985 (including Taylor Lecture No 9) (1986) NCRP PUBLICATIONS 10 11 12 13 14 15 16 17 18 19 20 21 / 279 Nonionizing Electromagnetic Radiations and Ultrasound, Proceedings of the Twenty-second Annual Meeting held on April 2-3, 1986 (including Taylor Lecture No 10) (1988) New Dosimetry at Hiroshima and Nagasaki 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) Radon, Proceedings of the Twenty-fourth Annual Meeting held on March 30-31, 1988 (including Taylor Lecture No 12) (1989) Radiation Protection Today—The NCRP at Sixty Years, Proceedings of the Twenty-fifth Annual Meeting held on April 5-6, 1989 (including Taylor Lecture No 13) (1990) Health and Ecological Implications of Radioactively Contaminated Environments, Proceedings of the Twenty-sixth Annual Meeting held on April 4-5, 1990 (including Taylor Lecture No 14) (1991) Genes, Cancer and Radiation Protection, Proceedings of the Twenty-seventh Annual Meeting held on April 3-4, 1991 (including Taylor Lecture No 15) (1992) Radiation Protection in Medicine, Proceedings of the Twentyeighth Annual Meeting held on April 1-2, 1992 (including Taylor Lecture No 16) (1993) Radiation Science and Societal Decision Making, Proceedings of the Twenty-ninth Annual Meeting held on April 7-8, 1993 (including Taylor Lecture No 17) (1994) Extremely-Low-Frequency Electromagnetic Fields: Issues in Biological Effects and Public Health, Proceedings of the Thirtieth Annual Meeting held on April 6-7, 1994 (not published) Environmental Dose Reconstruction and Risk Implications, Proceedings of the Thirty-first Annual Meeting held on April 12-13, 1995 (including Taylor Lecture No 19) (1996) Implications of New Data on Radiation Cancer Risk, Proceedings of the Thirty-second Annual Meeting held on April 3-4, 1996 (including Taylor Lecture No 20) (1997) The Effects of Pre- and Postconception Exposure to Radiation, Proceedings of the Thirty-third Annual Meeting held on April 2-3, 1997, Teratology 59, 181–317 (1999) Cosmic Radiation Exposure of Airline Crews, Passengers and Astronauts, Proceedings of the Thirty-fourth Annual Meeting held on April 1-2, 1998, Health Phys 79, 466–613 (2000) Radiation Protection in Medicine: Contemporary Issues, Proceedings of the Thirty-fifth Annual Meeting held on April 7-8, 1999 (including Taylor Lecture No 23) (1999) Lauriston S Taylor Lectures No Title The Squares of the Natural Numbers in Radiation Protection by Herbert M Parker (1977) 280 / 10 11 12 13 14 15 16 17 NCRP PUBLICATIONS Why be Quantitative about Radiation Risk Estimates? by Sir Edward Pochin (1978) Radiation Protection—Concepts and Trade Offs by Hymer L Friedell (1979) [Available also in Perceptions of Risk, see above] From ‘‘Quantity of Radiation’’ and ‘‘Dose’’ to ‘‘Exposure’’ and ‘‘Absorbed Dose’’—An Historical Review by Harold O Wyckoff (1980) How Well Can We Assess Genetic Risk? Not Very by James F Crow (1981) [Available also in Critical Issues in Setting Radiation Dose Limits, see above] Ethics, Trade-offs and Medical Radiation by Eugene L Saenger (1982) [Available also in Radiation Protection and New Medical Diagnostic Approaches, see above] The Human Environment—Past, Present and Future by Merril Eisenbud (1983) [Available also in Environmental Radioactivity, see above] Limitation and Assessment in Radiation Protection by Harald H Rossi (1984) [Available also in Some Issues Important in Developing Basic Radiation Protection Recommendations, see above] Truth (and Beauty) in Radiation Measurement by John H Harley (1985) [Available also in Radioactive Waste, see above] Biological Effects of Non-ionizing Radiations: Cellular Properties and Interactions by Herman P Schwan (1987) [Available also in Nonionizing Electromagnetic Radiations and Ultrasound, see above] How to be Quantitative about Radiation Risk Estimates by Seymour Jablon (1988) [Available also in New Dosimetry at Hiroshima and Nagasaki and its Implications for Risk Estimates, see above] How Safe is Safe Enough? by Bo Lindell (1988) [Available also in Radon, see above] Radiobiology and Radiation Protection: The Past Century and Prospects for the Future by Arthur C Upton (1989) [Available also in Radiation Protection Today, see above] Radiation Protection and the Internal Emitter Saga by J Newell Stannard (1990) [Available also in Health and Ecological Implications of Radioactively Contaminated Environments, see above] When is a Dose Not a Dose? by Victor P Bond (1992) [Available also in Genes, Cancer and Radiation Protection, see above] Dose and Risk in Diagnostic Radiology: How Big? How Little? by Edward W Webster (1992)[Available also in Radiation Protection in Medicine, see above] Science, Radiation Protection and the NCRP by Warren K Sinclair (1993)[Available also in Radiation Science and Societal Decision Making, see above] NCRP PUBLICATIONS 18 19 20 21 22 23 / 281 Mice, Myths and Men by R.J Michael Fry (1995) Certainty and Uncertainty in Radiation Research by Albrecht M Kellerer (1995) Health Phys 69, 446–453 70 Years of Radiation Genetics: Fruit Flies, Mice and Humans by Seymour Abrahamson (1996) Health Phys 71, 624–633 Radionuclides in the Body: Meeting the Challenge by William J Bair (1997) Health Phys 73, 423–432 From Chimney Sweeps to Astronauts: Cancer Risks in the Work Place by Eric J Hall (1998) Health Phys 75, 357–366 Back to Background: Natural Radiation and Radioactivity Exposed by Naomi H Harley (2000) Health Phys 79, 121–128 Symposium Proceedings No Title The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack, Proceedings of a Symposium held April 27-29, 1981 (1982) Radioactive and Mixed Waste—Risk as a Basis for Waste Classification, Proceedings of a Symposium held November 9, 1994 (1995) Acceptability of Risk from Radiation—Application to Human Space Flight, Proceedings of a Symposium held May 29, 1996 (1997) NCRP Statements No Title ‘‘Blood Counts, Statement of the National Committee on Radiation Protection,’’ Radiology 63, 428 (1954) ‘‘Statements on Maximum Permissible Dose from Television Receivers and Maximum Permissible Dose to the Skin of the Whole Body,’’ Am J Roentgenol., Radium Ther and Nucl Med 84, 152 (1960) and Radiology 75, 122 (1960) X-Ray Protection Standards for Home Television Receivers, Interim Statement of the National Council on Radiation Protection and Measurements (1968) Specification of Units of Natural Uranium and Natural Thorium, Statement of the National Council on Radiation Protection and Measurements (1973) NCRP Statement on Dose Limit for Neutrons (1980) Control of Air Emissions of Radionuclides (1984) The Probability That a Particular Malignancy May Have Been Caused by a Specified Irradiation (1992) The Application of ALARA for Occupational Exposures (1999) Extension of the Skin Dose Limit for Hot Particles to Other External Sources of Skin Irradiation (2001) 282 / NCRP PUBLICATIONS Other Documents The following documents of the NCRP were published outside of the NCRP report, commentary and statement series: Somatic Radiation Dose for the General Population, Report of the Ad Hoc Committee of the National Council on Radiation Protection and Measurements, May 1959, Science, February 19, 1960, Vol 131, No 3399, pages 482-486 Dose Effect Modifying Factors In Radiation Protection, Report of Subcommittee M-4 (Relative Biological Effectiveness) of the National Council on Radiation Protection and Measurements, Report BNL 50073 (T-471) (1967) Brookhaven National Laboratory (National Technical Information Service Springfield, Virginia) Index Carcinogenic effects in laboratory animals 99 Case-control studies 136 Categories of DNA damage 26 Cell-cycle checkpoints 31, 32 Characteristics and multistage nature of carcinogenesis in model systems 99 Chernobyl accident 38 Chromatid-type aberrations 51 Chromosome aberration dose response 59 Chromosomal aberrations 21, 52, 53, 61 adaptive response 61 low linear-energy transfer radiations 53 mechanisms 52 Chromosomal changes and cancer 71 Chromosomal instability 67 Chromosome aberrations 3, 50, 52, 53, 55, 56, 57, 60, 61, 62, 63 adaptive response 61 Chromatid aberrations 52, 55, 56, 57, 60, 62, 63, 69 distribution 56 dose-response curves 55 efficiency of DNA repair 62 genomic instability 63 high linear-energy transfer radiations 55 induced repair 63 intercellular distribution 57 inter- and intrachrosomal distributions 57 low linear-energy transfer radiations mechanisms 52 threshold response 60 Absorbed dose 11 Adaptive reactions Adaptive response(s) 3, 6, 33, 46, 95, 202, 204, 205 dose-response relationships 202 implications for the linearnonthreshold model 205 influence of the dose rate 204 Adaptive response for chromosome aberrations 61 Animal in vivo studies 39 Apoptosis 32 Apparent thresholds 197 Atomic-bomb survivor data 38, 144 Average effect on independent targets 18 Base damage and loss 27 Base damages 26 Base excision repair 27 Base repair mismatches 30 Biological dosimetry for chromosome aberrations 74, 76, 77 acute exposures 74 chronic exposures 76 evidence for threshold and/or linearity in dose response 77 implications for dose response for carcinogenic effects 77 Biophysical 11 Bone cancer 107 Breakage first hypothesis 53 Breast cancer 162, 163, 164 Bystander effect 23, 34, 68, 89 Cancer induction 20 Cancer patients 38 Carcinogenesis 4, 25, 99 Carcinogenic effects in human populations—epidemiological data 131 283 284 / INDEX Chromosome-type aberrations 51, 52 Clonality of tumors 21 Cluster studies 133 Clustered damage 18 Cohort studies 137 Conclusion(s) 7, 208 Cross-links 26, 28 Cytogenetic instability 66, 68 Definition of low dose 16 Delayed chromatid aberrations 69 Delayed cytogenetic instability 66 Delayed instability 23 Deletions 37 Deletions of base pairs 36 Deterministic effects Dicentrics 51 Discussion and conclusions 208 Distribution of chromosome aberrations 56 DNA damage 2, 18, 25 DNA lesions 25 DNA-protein cross-links 28 DNA repair and processing 2, 25, 26, 27, 45 Dose Dose limits Dose-rate effects 44, 91 mutagenesis 44 Dose-response Dose-response curve for total solid cancer mortality 143 Dose-response curves 19, 59, 191, 194 chromosome aberration 59 interactions 194 modifying factors 191 Dose-response relationship for oncogenic transformation 83 Dose-response relationship in epidemiologic data 195 Dose-response relationships 2, 4, 9, 101, 138 Dose-response relationships for cell survival and for oncogenic transformation 87 Dose-response studies 37, 46 high-LET 46 low-LET 37 Dose thresholds 196 Dosimetry for chromosome aberrations 74, 76, 77 acute exposures 74 chronic exposures 76 evidence for threshold and/or linearity in dose response 77 implications for dose response for carcinogenic effects 77 Double-strand break repair 29 Double-strand breaks 26, 28 Ecologic studies 134 Effect of adaptive response 61 Effects of linear-energy transfer 30 Efficiency of DNA repair 62 Energy deposition(s) 11, 14 Epidemiological data 5, 131 Epidemiological studies 133, 134, 136, 137 case-control studies 136 cluster studies 133 cohort studies 137 ecological studies 134 Epigenetic changes Excess relative risk for total solid cancers 143 Exchange process 53 Executive summary Formation of tumors 71 Frequency-averaged specific energy 14 Frequency-averaged specific energy per event 17 Genetic background 45 Genetic changes Genetic recombination 36 Genomic instability 45, 63, 81, 94, 95, 100 Global repair 28 INDEX Harderian gland tumors 122 Homeostatic and other modifying factors 101 Homologous recombination 28, 29, 37 Hormesis 8, 195 Hormetic response Host susceptibility 191 Human in vivo studies 37 Illegitimate recombination 29 Impact of cell-cycle checkpoints and apoptosis 32 Implications of energy-deposition patterns 18, 20 Inactivation of cells 22 Induced mutants at the S1 locus 47 Inducibility of DNA repair and cell-cycle checkpoints 62, 63 Inducible DNA repair systems 45 Inhomogeneity of the microdistribution of energy 11 Interactions between radiation and other cancer risk factors or exposures 194 In utero irradiation 178, 180, 182, 184, 186, 187 Interaction processes 12 Intercellular distributions of chromosome aberrations 57 Interchanges 51 Inter- and intrachromosomal distribution of chromosome aberrations 57 Interchromosomal recombination 37 Intermolecular recombination 37 Interstitial deletions 51 Intrachromosomal recombination 37 Introduction Inverse dose-rate effect 44, 91 Inversions 51 In vivo studies 39 Joint effects 194 / 285 Laboratory animal experiments 99 Latent period 108 Leukemia 102, 146, 148, 151 Leukemia mortality dose response 146 Life shortening 123, 124, 127, 128, 129 death rate in relation to time after the start of irradiation 129 dose rate 128 dose-response relationships 124 fractionation 127 protraction 127 Life-span study 138 Lineal energy 16 Linear relation 18 Linearity 23, 196 Linearity of cell by a single lowLET Linearity of dose response 138 Linear-nonthreshold doseresponse 6, 8, Low dose 16, 17 Lung adenocarcinomas 119 Lung cancer 166, 167, 169, 170, 172, 174, 175, 177 Lung tumors 116 Lyphomas 102 Malignant bone tumor 106 Mammalian cell studies 41 Mammary cancer 115 Mammary carcinomas 111, 112 Mammary fibroadenomas 112 Mammary gland tumors 108, 114 Mammary tumor incidence 109 Mammary tumors 110, 114 Mean specific energy per event 15 Mechanisms of mutagenesis 36 Misrepair of DNA lesions 37 Mismatch repair 30 Misrepair, misreplication and chromosome aberration formation 40 Misrepair of lesions 286 / INDEX Modifying factors 191, 194 host susceptibility 191 interactions 194 radiation sensitivity 191 Modulation 92 Monoclonality of tumors 21 Mutagenesis 25, 36, 44 dose-rate effects 44 Mutagenicity of x rays at the HPRT locus 43 Mutation frequencies 38 Mutation(s) 3, 36 Mutations arising during repair 37 Mutations inherited by the offspring of atomic-bomb survivors 38 Multiply-damaged sites 26, 20 Myeloid leukemia 103, 105 Neoplastic transformation Nonhomologous recombination 28, 29, 37 Nonlinear and threshold responses 59 chromosome aberration 59 Oncogenic transformation 82, 84, 86, 88, 91, 92, 93, 94, 95 adaptive response 95 dose protraction 93 dose-rate effect 91, 92 effects of TPA 94 genomic instability 94 modulation 92 Oncogenic transformation by high-LET radiations 91 Oncogenic transformation frequencies 89 Oncogenic transformation in vitro and genomic instability 81 dose-response relationships 81 Osteosarcoma 106 Point mutations 36 Practical threshold 197 Programmed cell death 32 Promoting effects of urethane on the induction of thymic lymphoma 104 Quantitative characterization of energy deposition 14 Radiation sensitivity 191 Reciprocal translocations 51 Recombination 36 Rejoining distance 55 Relationship between initiallydamaged cells and tumorigenic cells 22 Renal cancer 120 Renal neoplasms 116 Repair Repair of DNA 31 Replication errors 36 Research needs 24, 34, 49, 79, 97, 130, 200, 206 biophysical 24 carcinogenic effects in laboratory animals 130 carcinogenic effects in human populations 200 chromosome aberrations 79 DNA repair and processing 34 epidemiology 200 mutagenesis 49 oncogenic transformation 97 Rings 51 Risk estimates 139 Risk estimates for radiationinduced leukemia 148 Skin tumors 118, 121 Simulated charged-particle tracks 12 Simulated tracks 13 Single event spectrum 14 Single-strand breaks 25, 26 Solid tumors 138, 142 Somatic mutations 21 Specific energy 14, 16 Specific-locus data 40 Spontaneous DNA damage 30 Stochastic effects 1, INDEX Strand breaks 26 Supralinear response Target volume(s) 11, 17 Threshold Threshold dose-response Threshold response 197 Threshold response for radiationinduced chromosome aberrations 60 Thymic lymphoma 102, 104, Thymic lymphoma in mice 103 Thyroid adenoma 118 Thyroid cancer 155, 156, 157, 159, 160 Thyroid carcinoma 117 Thyroid neoplasia 114 Total cancer 142 Total solid cancers 138, 139, 143 Track patterns 15 Track structure 11 / 287 Transcription-coupled repair 28 Transformants per surviving cell 90 Transformation by high linearenergy transfer radiations 91 Transformation of hamster embryo cells 85 Types of adaptive responses 202 Types of epidemiological studies 133 Uncertainties in shapes of doseresponse curves at low doses 59 Using epidemiologic data for lowdose risk assessment 131 Variations in dose-response curves 101 X-chromosome inactivation 21 ... description of the literature was not the goal of this Report but rather a critical evaluation of the linear- nonthreshold dose- response model The sources of all data that are cited herein have, nevertheless,... on the dose, the type of mutation scored, the LET and dose rate of the radiation, and the genetic background of the exposed cells The frequency of mutations induced by a given dose of low-LET radiation. .. Hence, although there is evidence that the magnitude of such effects may vary, depending on the LET of the radiation and dose rate of irradiation, a linearnonthreshold dose- response model (e.g.,