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i Health Effects of Exposure to Low Levels of Ionizing Radiation Beir V Committee on the Biological Effects of Ionizing Radiations Board on Radiation Effects Research Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C.1996
ii National Academy Press 2101 Constitution Avenue, N.W. Washington, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sci- ences, the National Academy of Engineering, and the Institute of Medicine. The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distin- guished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the fed- eral government on scientific and technical matters. Dr. Frank Press is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sci- ences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Robert M. White is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy mat- ters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal govern- ment and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Samuel O. Thier is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of further- ing knowledge and advising the federal government. Functioning in accordance with general poli- cies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is adminis- tered jointly by both Academies and the Institute of Medicine. Dr. Frank Press and Dr. Robert M. White are chairman and vice chairman, respectively, of the National Research Council. The study summarized in this report was supported by the Oak Ridge Associated Universities, acting for the Office of Science and Technology Policy's Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) under Purchase Order No. C-43892. International Standard Book Number 0-309-03995-9 (paper) 0-309-03997-5 (cloth) Library of Congress Catalog Card Number 89-64118 Copyright Â© 1990 by the National Academy of Sciences No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purposes of official use by the United States Government. Printed in the United States of America First Printing, December 1989 Second Printing, June 1990 Third Printing, January 1991 Fourth Printing, March 1995 Fifth Printing, September 1997
iii COMMITTEE ON THE BIOLOGICAL EFFECTS OF IONIZING RADIATIONS ARTHUR C. UPTON, Chairman, Department of Environmental Medicine, New York University Medical Center, New York, New York DANIEL L. HARTL, Vice Chairman, Department of Genetics, Washington University School of Medicine, St Louis, Missouri BRUCE B. BOECKER, Inhalation Toxicology Research Institute, Albuquerque, New Mexico KELLY H. CLIFTON, University of Wisconsin Clinical Cancer Center, Madison, Wisconsin CARTER DENNISTON, Department of Genetics, University of Wisconsin, Madison, Wisconsin EDWARD R. EPP, Division of Radiation Biophysics, Massachusetts General Hospital, Boston, Massachusetts JACOB I. FABRIKANT, Donner Laboratory, University of California, Berkeley, California DOUGLAS GRAHN, Argonne National Laboratory, Argonne, Illinois ERIC J. HALL, Radiological Research Laboratory, Columbia University, New York, New York DONALD E. HERBERT, Department of Radiology, University of South Alabama, Mobile, Alabama DAVID G. HOEL, National Institute of Environmental Health Science, Research Triangle Park, North Carolina GEOFFREY R. HOWE, National Cancer Institute of Canada, University of Toronto, Toronto, Ontario, Canada SEYMOUR JABLON, National Cancer Institute, Bethesda, Maryland ANN R. KENNEDY, Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania ALFRED G. KNUDSON, JR., Fox Chase Cancer Center, Philadelphia, Pennsylvania DUNCAN C. THOMAS, Department of Preventive Medicine, University of Southern California, Los Angeles, California DALE PRESTON, Scientific Advisor to the Committee, National Cancer Institute, Bethesda, Maryland
iv National Research Council Staff WILLIAM H ELLETT, Study Director, Board on Radiation Effects Research, Commission on Life Sciences RAYMOND D. COOPER, Senior Program Officer, Board on Radiation Effects Research, Commission on Life Sciences RICHARD E. MORRIS, Editor, National Academy Press Sponsor's Project Officer WILLIAM A. MILLS, Oak Ridge Associated Universities
v Preface BACKGROUND The National Research Council's committees on the Biological Effects of Ionizing Radiations (BEIR) have prepared a series of reports to advise the U.S. government on the health consequences of radiation exposures. The most recent of these reports "Health Risks of Radon and Other Internally Deposited Alpha- EmittersâBEIR IV" was published in 1988. The last BEIR report to address health effects from external sources of penetrating electromagnetic radiation such as x rays and gamma rays was the report by the BEIR III Committee, "The Effects on Populations of Exposure to Low Levels of Ionizing Radiation: 1980." That report relied heavily on the mortality experience of the Japanese A- bomb survivors from 1950 through 1974 as a basis for the risk estimates it contains. The need for replacement of the BEIR III report became obvious when it was determined that the long standing estimates of the radiation exposures received by the A-bomb survivors, that had been utilized by the BEIR III Committee, required extensive revision. Following a binational research program by U.S. and Japanese scientists, a reassessment of A-bomb dosimetry was largely completed in 1986 and a new program of survivor dose estimation was initiated by the Radiation Effects Research Foundation (RERF) at Hiroshima and Nagasaki. In addition, RERF scientists extended their follow- up of A-bomb survivor mortality through the year 1985. In April of 1986, the Office of Science and Technology Policy's Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) asked the National Research Council to form a new BEIR committee to
vi report on the effect of ionizing radiations on the basis of the new information that was becoming available. A purchase agreement between the Oak Ridge Associated Universities, acting for CIRRPC, and the National Research Council to fund the BEIR V Committee was concluded in June of 1986. CHARGE TO THE COMMITTEE The new BEIR V Committee was asked by CIRRPC to conduct a comprehensive review of the biological effects of ionizing radiations focusing on information that had been reported since the conclusion of the BEIR III study, and to the extent that available information permitted, provide new estimates of the risks of genetic and somatic effects in humans due to low-level exposures of ionizing radiation. These risk estimates were to address both internal and external sources of radiation, and the procedure by which these risk estimates are derived was to be documented. The Committee was also asked to discuss the uncertainty in their risk estimates and, where possible, quantitate these uncertainties including the consequences of any necessary assumptions. Finally, the Committee was asked to prepare a detailed final report of their findings in a form suitable for making health risk assessments and calculating the probability that an observed cancer may be due to radiation. The conclusions of the BEIR IV Committee concerning alpha particle emitters were to be summarized in this final report to an extent consistent with the BEIR V Committee's presentation, but additional review of the scientific literature on the effects on alpha particle radiation was not required. While the BEIR V Committee was asked to summarize radiation risk information in a way that is useful for formulating radiation control decisions, recommendations on standards or guidelines for radiation protection were specifically excluded under the terms of this study. ORGANIZATION OF THE STUDY To carry out the charge, the NRC appointed a committee of scientists experienced in radiation carcinogenesis, epidemiology, radiobiology, genetics, biostatistics, pathology, radiation dosimetry, radiology, mathematical modeling, and risk assessment. The study was conducted under the general guidance of the Board on Radiation Effects Research of the Commission on Life Sciences. To facilitate its work and to augment its expertise so as to encompass a wider spectrum of scientific subjects, the Committee solicited specific contributions from a number of scientific experts other than its own members.
vii These experts participated in the Committee's deliberations throughout the course of its work. The Committee held eight meetings over a period of 30 monthsâseven in Washington, D.C., and one in Woods Hole, Massachusetts. The second meeting, on March 2, and March 3, 1987 included a public meeting, at which open discussion and contributions from interested scientists and the public at large were invited. In addition, over a dozen meetings of subgroups of the Committee were held to plan and carry out specific work assignments. The Committee organized its work according to the main objectives of the charge and divided the study into the following categories: â¢ Heritable genetic effects. â¢ Cellular radiobiology and carcinogenic mechanisms. â¢ Radiation carcinogenesis. â¢ Radiation effects on the fetus. â¢ Radiation epidemiology and risk modeling. The expertise of the Committee, including its invited participants, permitted considerable overlapping of assignments among the different categories, ensuring interaction between scientific specialists in different disciplines.
ix Acknowledgments In order to respond to the broad charge to the Committee, the work of the Committee was assisted by a number of experts in selected scientific disciplines. The Committee wishes to acknowledge with thanks the valuable contributions of the Directors and Staff of the Radiation Effects Research Foundation, Hiroshima, Japan, for providing the most current Life Span Study data on the Japanese atomic-bomb survivors, and for new organ dose estimates based on the revised atomic-bomb dosimetry. These records have emerged as the most complete data base on the health effects of low-LET radiation exposure in human populations, and continue to be the most comprehensive that have been analyzed for purposes of risk estimation. The analyses presented in the Committee's report were made possible by computational programs developed at the Radiation Effects Research Foundation; Dale Preston, who was responsible for much of their development, served as Scientific Advisor to the Committee, and provided invaluable aid during the course of its deliberations. The preparation of the report required broad scientific experience in several interrelated disciplines. In this regard, the Committee acknowledges the special help, effort and time of a number of invited participants, and especially Sarah C. Darby, James V. Neel, Susan Preston-Martin, Elaine Ron, William J. Schull, Oddvar Nygaard, and Roy Shore. All of these scientists provided scientific data, advice, and help in the preparation or review of scientific sections of the report, and gave freely of their time and scientific expertise. The Committee would also like to thank Dr. Alice
x Stewart for meeting with the Committee's cancer risk group and providing advance copies of the paper on the A-bomb survivors she presented at the 14th Gray Conference, Oxford, 1988. Very special thanks are extended to Lea Arnold, Doris E. Taylor, and Collette A. Carmi, for their administrative support and for preparation of the many drafts of the report. Their tasks were done with speed and good humor; they were invaluable in assisting the members of the Committee in the completion of their work. ARTHUR UPTON, CHAIRMAN
CONTENTS xi Contents Executive Summary 1 1 Background Information and Scientific Principles 9 Physics and Dosimetry of Ionizing Radiation 9 Population Exposure to Ionizing Radiation in the 17 United States Radiobiological Concepts 20 Effects of Radiation on Genes and Chromosomes 31 Internally Deposited Radionuclides: Special Con- 38 siderations Use of Animal Studies 42 Epidemiological Studies: Special Considerations 44 Risk Assessment Methodology 49 2 Genetic Effects of Radiation 65 Introduction 65 Summary of Conclusions 68 Methods of Risk Calculation 71 Previous Estimates of Human Doubling Dose 74 Calculation of Risk Estimates 77 Background Data from Humans 90 Background Data from Mice and Other Mammals 97 3 Mechanisms of Radiation-Induced Cancer 135 Background 135 Mechanisms 136
CONTENTS xii Genetics of Cancer 145 Effects of Age, Sex, Smoking, and Other Suscepti- 152 bility Factors 4 Risk of CancerâAll Sites 161 Introduction 161 Model Fitting 163 Risk Assessment 171 Uncertainty in Point Estimates of Lifetime Risk 176 ANNEX 4A Summary of Major Epidemiologic Studies Used in 182 BEIR V ANNEX 4B Changes in the Estimated Dose for A-Bomb Sur- 190 vivors ANNEX 4C AMFIT 196 ANNEX 4D The Committee's Analysis of A-Bomb Survivor Data 198 ANNEX 4E Modeling Breast Cancer 205 ANNEX 4F Uncertainty, Probability of Causation, and Diagnos- 217 tics ANNEX 4G The BEIR IV Committee's Model and Risk Esti- 239 mates for Lung Cancer Due to Radon Progeny 5 Radiogenic Cancer at Specific Sites 242 Leukemia 242 Breast 253 Lung 267 Stomach 278 Thyroid 281 Esophagus 298 Small Intestine 300 Colon and Rectum 301 Liver 303 Skeleton 306 Brain and Nervous System 310 Ovary 313 Uterus 314 Testis 315 Prostate 316 Urinary Tract 318 Parathyroid Glands 321 Nasal Cavity and Sinuses 324 Skin 325 Lymphoma and Multiple Myeloma 327
CONTENTS xiii Pharynx, Hypopharynx, and Larynx 330 Salivary Glands 331 Pancreas 333 6 Other Somatic and Fetal Effects 352 Cancer in Childhood Following Exposure In Utero 352 Effects on Growth and Development 354 Cataract of the Eye Lens 363 Life Shortening 363 Fertility and Sterility 364 7 Low Dose Epidemiologic Studies 371 Introduction 371 Diagnostic Radiography: Adult-Onset Myeloid 371 Leukemia Fallout from Nuclear Weapons Testing 373 Cancer among Individuals Near Nuclear Installations 377 Epidemiologic Studies of Workers Exposed to Low 379 Dose, Low-LET Radiation High Natural Background Radiation 383 Glossary 391 Index 401