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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? Health Effects of Exposure to Low Levels of Ionizing Radiations TIME FOR REASSESSMENT? Committee on Health Effects of Exposure to Low Levels of Ionizing Radiations (BEIR VII) Board on Radiation Effects Research Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, DC 1998
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? 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 competencies and with regard for appropriate balance. This report was prepared under EPA Assist ID No. X825133-01-0 between the National Academy of Sciences and the US Environmental Protection Agency. ISBN: 0-309-06176-8 A limited number of copies of this report are available from National Research Council Board on Radiation Effects Research Room 342 2101 Constitution Avenue, NW Washington, DC 20418 (202) 334-2232 Copyright 1998 by the National Academy of Sciences. All rights reserved. Printed in the United States of America
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? COMMITTEE ON HEALTH EFFECTS OF EXPOSURE TO LOW LEVELS OF IONIZING RADIATIONS (BEIR VII) PHASE I RICHARD B. SETLOW (Chair), Brookhaven National Laboratory, Upton, New York KENNETH H. CHADWICK, Radiation Protection Research Unit, European Commission, Brussels, Belgium PHILIP C. HANAWALT, Stanford University, Stanford, California GEOFFREY R. HOWE, Columbia University, New York, New York ALBRECHT M. KELLERER, Strahlenbiologisches Institut der Ludwig-Maximilians-Universität, Munich, Germany CHARLES E. LAND, National Cancer Institute, Rockville, Maryland NANCY L. OLEINICK, Case Western Reserve University, Cleveland, Ohio ROBERT L. ULLRICH, The University of Texas Medical Branch at Galveston, Texas CLS ADVISER CHARLES F. STEVENS, The Salk Institute for Biological Studies, La Jolla, California NATIONAL RESEARCH COUNCIL STAFF EVAN B. DOUPLE, Study Director and Director, Board on Radiation Effects Research (effective March 1997) RICK JOSTES, Senior Program Officer (effective August 1997) STEVEN L. SIMON, Senior Program Officer (effective January 1997) PEGGY Y. JOHNSON, Project Assistant (effective December, 1997) DORIS E. TAYLOR, Staff Assistant NORMAN GROSSBLATT, Editor SPONSOR'S PROJECT OFFICER Jerome Puskin, US Environmental Protection Agency
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? BOARD ON RADIATION EFFECTS RESEARCH JOHN B. LITTLE (Chair), Harvard School of Public Health, Boston, Massachusetts VALERIE BERAL, University of Oxford, United Kingdom* MERRIL EISENBUD, Chapel Hill, North Carolina (deceased September 1997) MAURICE S. FOX, Massachusetts Institute of Technology, Cambridge, Massachusetts R.J. MICHAEL FRY, Oak Ridge, Tennessee PHILIP C. HANAWALT, Stanford University, Stanford, California LYNN W. JELINSKI, Cornell University, Ithaca, New York* WILLIAM J. SCHULL, The University of Texas Health Science Center at Houston, Texas DANIEL O. STRAM, University of Southern California, Los Angeles, California* SUSAN W. WALLACE, University of Vermont, Burlington, Vermont H. RODNEY WITHERS, UCLA Medical Center, Los Angeles, California NATIONAL RESEARCH COUNCIL STAFF EVAN B. DOUPLE, Director, Board on Radiation Effects Research (effective March 1997) RICK JOSTLES, Senior Program Officer (effective August 1997) STEVEN L. SIMON, Senior Program Officer (effective January 1997) CATHERINE S. BERKLEY, Administrative Associate KAREN BRYANT, Project Assistant (effective February 1997) PEGGY JOHNSON, Project Assistant (effective December 1997) DORIS E. TAYLOR, Staff Assistant * New BRER members effective July 1997
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? COMMISSION ON LIFE SCIENCES THOMAS D. POLLARD (Chair), The Salk Institute for Biological Studies, La Jolla, California FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, DC JOHN C. BAILAR III, University of Chicago, Chicago, Illinois PAUL BERG, Stanford University School of Medicine, Stanford, California JOANNA BURGER, Rutgers University, Piscataway, New Jersey JOHN L. EMERSON, Indianapolis, Indiana NEAL L. FIRST, University of Wisconsin, Madison, Wisconsin SHARON L. DUNWOODY, University of Wisconsin, Madison, Wisconsin URSULA W. GOODENOUGH, Washington University, St. Louis, Missouri HENRY W. HEIKKINEN, University of Northern Colorado, Greeley, Colorado HANS J. KENDE, Michigan State University, East Lansing, Michigan CYNTHIA J. KENYON, University of California, San Francisco, California DAVID M. LIVINGSTON, Dana-Father Cancer Institute, Boston, Massachusetts THOMAS E. LOVEJOY, Smithsonian Institution, Washington, DC DONALD R. MATTISON, University of Pittsburgh, Pittsburgh, Pennsylvania JOSEPH E. MURRAY, Wellesley Hills, Massachusetts EDWARD E. PENHOET, Chiron Corporation, Emeryville, California MALCOLM C. PIKE, Norris/USC Comprehensive Cancer Center, Los Angeles, California JONATHAN M. SAMET, The Johns Hopkins University, Baltimore, Maryland CHARLES F. STEVENS, The Salk Institute for Biological Studies, La Jolla, California JOHN L. VANDEBERG, Southwest Foundation for Biomedical Research, San Antonio, Texas NATIONAL RESEARCH COUNCIL STAFF PAUL GILMAN, Executive Director ALVIN G. LAZEN, Associate Executive Director BARBARA SMITH, Administrative Officer
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished 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 federal government on scientific and technical matters. Dr. Bruce M. Alberts 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 Sciences 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. William A. Wulf 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 matters 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 government and, upon its own initiative, to identify issues of medical care, research, and education Dr. Kenneth I. Shine is president of the Institute. 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 furthering knowledge and advising the federal government Functioning in accordance with general policies de trained 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 administered jointly by both Academies and the Institute of Medicine, Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? Preface Humans have always lived in the presence of low levels of ionizing radiation arising from cosmic rays and emissions from radioisotopes in the air, in water, and on the land. Relatively small populations receive a range, usually small amounts, of occupational exposures, or are exposed to larger doses from diagnostic or therapeutic medical procedures. Other groups have received exposures from radioactive fallout from bomb tests, or from radiation accidents such as Chernobyl. New information has become available in recent years on large exposures of workers in nuclear facilities in the former Soviet Union and on populations affected by their hazardous wastes. In the latter case, precise doses are often difficult to establish, but the data are of particular relevance to radiation protection because they relate to long term low dose-rate exposures. However, the observations on the atomic-bomb survivors in Hiroshima and Nagasaki continue to be the main source of information. The health effects of acute or chronic ionizing-radiation exposure, such as cancer, are superimposed on the effects that arise from endogenous chemical reactions or exogenous exposures to carcinogens in the environment. Radiation is different from other carcinogens in that in principle it is possible, even if often difficult, to estimate radiation doses whereas, although the mechanisms of action of many chemical carcinogens have been elucidated, environmental- or occupational-exposure doses are poorly known if at all. The ability to measure radiation doses implies that it is possible to quantify the hazard so as to estimate the mortality arising from low doses of radiation. Low-dose radiation effects cannot be estimated by direct observation, because of the large numbers of background cancers arising from other causes, which usually are not known. For high acute exposures, as in Japan, or for some medical procedures, sufficiently precise data can be obtained to permit extrapolation to lower acute exposures or to lower chronic exposures, assuming a knowledge of the relation between effect and dose and the effect of dose rate. However, extrapolation to low exposures is attended by large uncertainties because the shape of dose-response curves is not well known, especially at the lower doses, and because of uncertainty in background levels (zero added dose). Often, in the absence of reliable data, it is assumed that extrapolation to low doses should be linear and without a threshold, a straight line connecting high dose with zero radiation dose (and zero excess cancers). That point of view is controversial. Some investigators believe that there is a threshold dose—a dose below which radiation has no deleterious effect. Others cite data indicating that the shape of a dose-response curve close to the zero dose has a slope much greater than that of the straight-line that represents interpolation between zero dose and high doses. The uncertainties in the magnitude of low-dose effects led to a request from the US Environmental Protection Agency (EPA) to the National Research Council that a committee be formed to consider recent data derived from molecular, cellular, animal, and human epidemiologic studies and to evaluate whether it would be feasible to improve the estimated risks to humans posed by exposures to low levels of ionizing radiation. As a result, the Research Council's Commission on Life Sciences authorized the Board on Radiation Effects Research (BRER) to form the Committee on Health Effects of Exposure to Low Levels of Ionizing Radiations (referred to as BEIR VII because it is the seventh committee
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? in a series that began with the Committee on Biological Effects of Ionizing Radiations). The Committee was to carry out a preliminary scoping (phase-1 study) to review and evaluate the scientific literature pertinent to the biologic and health effects of low-level ionizing radiation and make a concerted effort to learn about the status of all relevant research in progress. The committee was charged to determine, on the basis of those data, whether sufficient information had become available since the 1990 BEIR V report to warrant a comprehensive reassessment of health risks in a phase-2 study by an enlarged BEIR VII committee. The phase-1 committee, organized in January 1997, had 8 members with expertise in molecular, cellular and animal radiation biology and in human epidemiology and radiation dosimetry. The committee met first in March to summarize what it knew about relevant advances since the 1990 BEIR V report and to organize 2 workshops. The workshops were to encompass invited speakers and position papers at publicized meetings on epidemiology and on the impact of new biologic knowledge on risk assessment. A 2-day committee meeting in June included a half-day workshop devoted to epidemiology and a 2-1/2 day committee meeting in July included 2 days devoted to the impact of new biologic knowledge on risk assessment. A 2-day meeting in August, overlapping a BRER meeting, was devoted to summarizing the committee's conclusions derived from the members' own reading, discussion, and the workshops and to begin the writing of the committee's report. This BEIR VII phase-1 report includes an executive summary recommending a full, BEER VII phase-2 study, and describes the general structure of the phase-2 study. Chapters on epidemiology, cellular and molecular considerations, animal studies, and mechanistic cancer modeling provide the background information for a phase-2 study and the committee's rationale for endorsing such a study. Richard B. Setlow, Chairman
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? Contents EXECUTIVE SUMMARY 1 1. INTRODUCTION 5 2. EPIDEMIOLOGIC INVESTIGATIONS 6 New Epidemiologic Results 6 Advances in Methodology 12 Considerations for a BEIR VII phase-2 Committee 12 Radioepidemiologic Tables 13 3. CELLULARY AND MOLECULAR CONSIDERATIONS 14 DNA Damage and Its Repair 14 Conclusions 20 Conditioned and Inducible Responses to Radiation 20 Conclusions 24 Chromosomal Aberrations and Mutations 24 Chromosomal Aberrations 25 Mutations 28 Conclusions 30 4. ANIMAL STUDIES 30 Conclusions 32 5. RADIO BIOLOGICAL PRINCIPLES AND RISK MODELING 33 Linearity Versus Curvilinearity 33 Dose Dependence of RBE 35 Potential Impact of Neutrons 38 Conclusions 41
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Health Effects of Exposure to Low Levels of Ionizing Radiations: Time for Reassessment? 6. MATHEMATICAL MODELS OF RADIATION CARCINOGENESIS 41 The Two-Mutation Model 42 Implications of the Model for Risk Estimation 45 Conclusions 50 LITERATURE CITED 51 INFORNATION ON COMMITTEE 73 LIST OF ACRONYMS 75 ACKNOWLEDGMENTS 76