HEALTH RISKS FROM EXPOSURE TO LOW LEVELS OF IONIZING RADIATION

BEIR VII PHASE 2

Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation

Board on Radiation Effects Research

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page R1
HEALTH RISKS FROM EXPOSURE TO LOW LEVELS OF IONIZING RADIATION BEIR VII PHASE 2 Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation Board on Radiation Effects Research Division on Earth and Life Studies

OCR for page R1
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 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 study was supported by funds from the U.S. Department of Defense, U.S. Department of Energy, and U.S. Environmental Protection Agency through EPA Grant #X-82684201, the Nuclear Regulatory Commis- sion through NRC Grant #NRC-04-98-061, and the U.S Department of Homeland Security through U.S. De- partment of Commerce, National Institute of Standards and Technology Grant #60NANB5D1003. Any opin- ions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project. Library of Congress Cataloging-in-Publication Data Health risks from exposure to low levels of ionizing radiation : BEIR VII, Phase 2 / Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, Board on Radiation Effects, Research Division on Earth and Life Studies, National Research Council of the National Academies. p. cm. This is the seventh in a series of reports from the National Research Council prepared to advise the U.S. government on the relationship between exposure to ionizing radiation and human health. Includes bibliographical references and index. ISBN 0-309-09156-X (pbk.) — ISBN 0-309-53040-7 (pdf) 1. Ionizing radiation—Toxicology. 2. Ionizing radiation—Physiological effect. 3. Ionizing radiation—Dose-response relationship. I. National Research Council (U.S.). Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation. RA1231.R2H395 2006 363.17′99—dc22 2006000279 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. Copyright 2006 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

OCR for page R1
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. Ralph J. Cicerone 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 engi- neers. Dr. Wm. 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 congres- sional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg 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 furthering knowledge and advis- ing the federal government. Functioning in accordance with general policies 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 engineer- ing communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

OCR for page R1
COMMITTEE TO ASSESS HEALTH RISKS FROM EXPOSURE TO LOW LEVELS OF IONIZING RADIATION RICHARD R. MONSON (chairman), Harvard School of Public Health, Boston, MA JAMES E. CLEAVER (vice chairman), University of California, San Francisco, CA HERBERT L. ABRAMS, Stanford University, Stanford, CA EULA BINGHAM, University of Cincinnati, Cincinnati, OH PATRICIA A. BUFFLER, University of California, Berkeley, CA ELISABETH CARDIS, International Agency for Research on Cancer, Lyon, France ROGER COX, National Radiological Protection Board, Chilton, Didcot, Oxon, United Kingdom SCOTT DAVIS, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA WILLIAM C. DEWEY, University of California, San Francisco, CA ETHEL S. GILBERT, National Cancer Institute, Rockville, MD ALBRECHT M. KELLERER, Ludwig-Maximilians-Universität, München, Germany DANIEL KREWSKI, University of Ottawa, Ottawa, Ontario, Canada TOMAS R. LINDAHL, Cancer Research UK London Research Institute, United Kingdom KATHERINE E. ROWAN, George Mason University, Fairfax, VA K. SANKARANARAYANAN, Leiden University Medical Centre, Leiden, The Netherlands DANIEL W. SCHAFER, Oregon State University, Corvallis, OR (from May 2002) LEONARD A. STEFANSKI, North Carolina State University, Raleigh, NC (through May 2002) ROBERT L. ULLRICH, Colorado State University, Fort Collins, CO CONSULTANTS JOHN D. BOICE, JR., International Epidemiology Institute, Rockville, MD KIYOHIKO MABUCHI, National Cancer Institute, Rockville, MD

OCR for page R1
NATIONAL RESEARCH COUNCIL STAFF RICK JOSTES, Study Director EVAN B. DOUPLE, BRER Director DONALD A. PIERCE, Research Adviser Radiation Effects Research Foundation COURTNEY GIBBS, Program Assistant DORIS E. TAYLOR, Staff Assistant CATHIE BERKLEY, Financial Officer BOARD ON RADIATION EFFECTS RESEARCH S. JAMES ADELSTEIN (chairman), Harvard Medical School, Boston, MA HAROLD L. BECK, Department of Energy Environmental Laboratory (retired), New York, NY JOEL S. BEDFORD, Colorado State University, Fort Collins, CO JAMES E. CLEAVER, University of California San Francisco Cancer Center, San Francisco, CA SARAH C. DARBY, University of Oxford, Oxford, United Kingdom SHARON L. DUNWOODY, University of Wisconsin, Madison, WI C. CLIFTON LING, Memorial Sloan-Kettering Cancer Center, New York, NY DANIEL KREWSKI, University of Ottawa, Ottawa, Ontario, Canada THEODORE L. PHILLIPS, University of California, San Francisco, CA ANDREW M. SESSLER, E.O. Lawrence Berkeley National Laboratory, Berkeley, CA JOHN C. VILLFORTH, Food and Drug Law Institute (retired), Derwood, MD PAUL L. ZIEMER, Purdue University, West Lafayette, IN NATIONAL RESEARCH COUNCIL STAFF EVAN B. DOUPLE, Director, Board on Radiation Effects Research ISAF AL-NABULSI, Senior Program Officer RICK JOSTES, Senior Program Officer CATHERINE S. BERKLEY, Administrative Associate COURTNEY GIBBS, Program Assistant DORIS TAYLOR, Staff Assistant

OCR for page R1

OCR for page R1
Preface and dose-rate effectiveness factor, relative biologic effec- BACKGROUND tiveness, genomic instability, and adaptive responses) and This is the seventh in a series of reports from the National appropriate methods to develop etiologic models (favoring Research Council (NRC) prepared to advise the U.S. gov- simple as opposed to complex models) and estimate popula- ernment on the relationship between exposure to ionizing tion detriment; (4) assess the current status and relevance to radiation and human health. In 1996 the National Academy risk models of biologic data and models of carcinogenesis, of Sciences (NAS) was requested by the U.S. Environmental including critical assessment of all data that might affect the Protection Agency to initiate a scoping study preparatory to shape of the response curve at low doses, in particular, evi- a new review of the health risks from exposure to low levels dence for or against thresholds in dose-response relation- of ionizing radiations. The main purpose of the new review ships and evidence for or against adaptive responses and ra- would be to update the Biological Effects of Ionizing Radia- diation hormesis; (5) consider, when appropriate, potential tion V (BEIR V) report (NRC 1990), using new information target cells and problems that might exist in determining dose from epidemiologic and experimental research that has accu- to the target cell; and (6) consider any recent evidence re- mulated during the 14 years since the 1990 review. Analysis garding genetic effects not related to cancer. In performing of those data would help to determine how regulatory bodies the above tasks, the committee should consider all relevant should best characterize risks at the doses and dose rates data, even if obtained from high radiation exposures or at experienced by radiation workers and members of the gen- high dose rates. eral public. BEIR VII—Phase 1 was the preliminary survey With respect to modeling, the committee will (1) develop to evaluate whether it was appropriate and feasible to con- appropriate risk models for all cancer sites and other out- duct a BEIR VII—Phase 2 study. The Phase 1 study deter- comes for which there are adequate data to support a quanti- mined that it was appropriate and feasible to proceed to Phase tative estimate of risk, including benign disease and genetic 2. The Phase 1 study, Health Effects of Exposure to Low effects; (2) provide examples of specific risk calculations Levels of Ionizing Radiations: Time for Reassessment?, based on the models and explain the appropriate use of the published in 1998, also provided the basis for the Phase 2 risk models; (3) describe and define the limitations and un- Statement of Task that follows. certainties of the risk models and their results; (4) discuss the role and effect of modifying factors, including host (such as individual susceptibility and variability, age, and sex), BEIR VII—PHASE 2 STATEMENT OF TASK environment (such as altitude and ultraviolet radiation), and The primary objective of the study is to develop the best life-style (such as smoking history and alcohol consump- possible risk estimate for exposure to low-dose, low linear tion) factors; and (5) identify critical gaps in knowledge that energy transfer (LET) radiation in human subjects. In order should be filled by future research. to do this, the committee will (1) conduct a comprehensive review of all relevant epidemiologic data related to the risk WHAT HAS CHANGED SINCE THE LAST BEIR REPORT from exposure to low-dose, low-LET radiation; (2) define ON THE HEALTH EFFECTS OF LOW LEVELS OF and establish principles on which quantitative analyses of LOW-LET IONIZING RADIATION low-dose and low-dose-rate effects can be based, including requirements for epidemiologic data and cohort characteris- In the 15 years since the publication of the previous BEIR tics; (3) consider relevant biologic factors (such as the dose report on low-LET radiation (BEIR V), much new informa- vii

OCR for page R1
viii PREFACE tion has become available on the health effects of ionizing from any apparent or potential conflict of interest. The work radiation. Since the 1990 BEIR V report, substantial new of the committee was conducted with the assistance of the information on radiation-induced cancer has become avail- Board of Radiation Effects Research of the Division on Earth able from the Hiroshima and Nagasaki survivors, slightly and Life Sciences. less than half of whom were alive in 2000. Of special impor- The committee held 11 meetings over a period of tance are cancer incidence data from the Hiroshima and 4.5 years. The long duration of the committee was due Nagasaki tumor registries. The committee evaluated nearly largely to a period of reduced activity while awaiting 13,000 incidences of cancer and approximately 10,000 can- completion of the update of the dosimetry and exposure esti- cer deaths in contrast to fewer than 6000 cancer deaths avail- mates to atomic bomb survivors of Hiroshima and Nagasaki, able to the BEIR V committee. Also, since completion of the Japan (the so-called DS02: Dosimetry System 2002). 1990 report, additional evidence has emerged from studies Six of the meetings included participation of the public of the Hiroshima and Nagasaki atomic bomb survivors sug- for a portion of the meeting, and five of the meetings were gesting that other health effects, such as cardiovascular dis- conducted exclusively in executive session. Each meeting ease and stroke, can result from radiation exposure. included extensive deliberations involving the committee as A major reevaluation of the dosimetry at Hiroshima and a whole; in addition, two major subcommittees were formed Nagasaki has recently been completed that lends more cer- that were termed “biology” and “epidemiology.” Dr. Monson tainty to dose estimates and provides increased confidence convened the epidemiology sessions and Dr. Cleaver con- in the relationship between radiation exposure and the health vened the biology sessions. Also, a number of loosely orga- effects observed in Japanese A-bomb survivors. Additional nized and nonpermanent working groups were formed to new information is also available from radiation worker stud- discuss the many issues before the committee. This enabled ies, medical radiation exposures, and populations with envi- biologists and nonbiologists to work together and evaluate ronmental exposures. each other’s work. Although the cancer risk estimates have not changed greatly since the 1990 report, confidence in the estimates has ORGANIZATION OF THE REPORT risen because of the increase in epidemiologic and biologi- cal data available to the committee. As noted under its STATEMENT OF TASK, the com- Progress has also been made since the 1990 report in ar- mittee’s focus was to develop the best possible risk estimate eas of science that relate to the estimation of genetic (heredi- for exposure to low-dose, low-LET radiation in human sub- tary) effects of radiation. In particular, (1) advances in hu- jects. Accordingly, Chapters 1–4 discuss basic aspects of man molecular biology have been incorporated into the radiation physics and radiation biology, including the known conceptual framework of genetic risk estimation, and (2) it interaction between radiation exposure and genetic material, has become possible to project risks for all classes of genetic cellular structures, and whole organisms. Chapters 5–9 dis- diseases (i.e., those with more complex as well as simple cuss basic principles of epidemiology as well as substantive patterns of inheritance). data relating to exposure from the atomic bombs, medical Advances in cell and molecular biology have also con- radiation, occupational radiation, and environmental radia- tributed new information on the mechanisms through which tion. Chapters 10–12, to the extent possible, integrate the cells respond to radiation-induced damage and to the close information from biology and epidemiology and develop risk associations between DNA damage response and cancer de- estimates based on this information. Three summary sec- velopment. tions provide different levels of description of the report. Chapter 13 is an overall scientific summary and lays out the research needs identified by the committee. The Executive ORGANIZATION OF THE STUDY Summary is an abbreviated and reorganized version of Chap- The NRC appointed a committee comprised of scientists ter 13 that provides an overview of the report. The Public and educators. Some had particular expertise in conducting Summary addresses the findings of the committee and the research on ionizing radiation, while others were experi- relevance of the report to public concerns about exposure to enced in fields relevant to the committee’s charge. The NRC ionizing radiation. vetted all potential members to ensure that each was free

OCR for page R1
Reviewers This report has been reviewed in draft form by persons Chris G. Whipple, ENVIRON International Corporation, chosen for their diverse perspectives and technical expertise Emeryville, CA in accordance with procedures approved by the National Research Council’s Report Review Committee. The pur- Although the reviewers listed above have provided many poses of this review are to provide candid and critical com- constructive comments and suggestions, they were not asked ments that will assist the institution in making the published to endorse the conclusions or recommendations, nor did they report as sound as possible and to ensure that the report meets see the final draft of the report before its release. The review institutional standards of objectivity, evidence, and respon- of this report was overseen by George M. Hornberger, Ernest siveness to the study charge. The review comments and draft H. Ern Professor of Environmental Sciences and Associate manuscript remain confidential to protect the integrity of the Dean for the Sciences, University of Virginia, and John C. deliberative process. We wish to thank the following for their Bailar III, Professor Emeritus, University of Chicago. Ap- participation in the review of this report: pointed by the National Research Council, they were respon- sible for making certain that an independent examination of Seymour Abrahamson, University of Wisconsin, Madison, this report was carried out in accordance with institutional WI procedures and that all review comments were carefully con- John F. Ahearne, Sigma Xi, The Scientific Research sidered. Responsibility for the final content of this report Society, Research Triangle Park, NC rests entirely with the authoring committee and the National Allan Balmain, University of California, San Francisco, Research Council. CA Michael Cornforth, University of Texas, Galveston, TX James F. Crow, University of Wisconsin, Madison, WI GENERAL ACKNOWLEDGMENTS John Easton, University of Chicago Hospitals, Chicago, IL Eric J. Hall, Columbia University College of Physicians The committee thanks the directors and staff of the Ra- and Surgeons, New York, NY diation Effects Research Foundation (RERF), Hiroshima, Richard D. Hichwa, University of Iowa, Iowa City, IA Japan, for providing the most current Life Span Study data Hedvig Hricak, Memorial Sloan-Kettering Cancer Center, on the Japanese atomic bomb survivors. These data continue New York, NY to be the primary source of epidemiologic information on Glenn F. Knoll, University of Michigan, Ann Arbor, MI the relationship between exposure to ionizing radiation and Jack S. Mandel, Emory University Rollins School of its effects on human health. In particular, Dr. Donald Pierce Public Health, Atlanta, GA was especially helpful in communication between RERF and John P. Murnane, University of California, San Francisco, the committee; he also added his insightful experience to the CA work of the committee. Hooshang Nikjoo, National Aeronautics and Space The committee was aided in the consideration of its Administration, Houston, TX charge not only by comments from the public but also by Jonathan M. Samet, Johns Hopkins University, Baltimore, formal presentations by experts from a number of fields. The MD following presentations were made as part of the public por- Susan S. Wallace, University of Vermont, Burlington, VT tion of the meetings (in order of appearance): ix

OCR for page R1
x REVIEWERS Presentations by Sponsors Al Fornace, Ph.D. Harvard School of Public Health Jerome Puskin, Ph.D. Functional genomics and informatics approaches to Environmental Protection Agency categorize radiation response Vincent Holahan, Ph.D. Steve Wing, Ph.D. U.S. Nuclear Regulatory Commission University of North Carolina Relevance of occupational epidemiology to radiation risk Bonnie Richter, Ph.D. assessment U.S. Department of Energy Edward Calabrese, Ph.D. Scientific Speakers University of Massachusetts Radiation hormesis John Boice, Ph.D. International Epidemiology Institute David Utterback, Ph.D. Epidemiology that should be considered by BEIR VII National Institute of Occupational Safety and Health Exposure assessment and radiation worker studies Charles Waldren, Ph.D. Colorado State University Sharon Dunwoody, Ph.D. Adaptive effects, genomic instability, and bystander effects University of Wisconsin Challenges in the communication of scientific uncertainties John Ward, Ph.D. University of California, San Diego Suresh Moolgavkar, Ph.D., M.B.B.S. Differences between ionizing radiation-induced DNA School of Public Health and Community Medicine, damage and endogenous oxidative damage University of Washington and Fred Hutchinson Cancer Research Center Antone Brooks, Ph.D. Biology-based models Washington State University Tri-cities Overview of projects funded by the Department of Energy We thank these presenters and all other members of the low-dose program public who spoke on issues related to ionizing radiation. The committee thanks Dr. Isaf Al-Nabulsi for her assis- Charles Land, Ph.D. tance at the beginning of this study and Doris Taylor and National Institutes of Health (NIH) Cathie Berkley for their administrative assistance in assur- National Cancer Institute’s update of the 1985 NIH ing that its members showed up at the right place at the right Radioepidemiologic Tables time. The committee was also aided in its work by a talented group of program assistants. We thank Courtney Gibbs for L.B. Russell, Ph.D. her assistance in the preparation of this manuscript. We thank Oak Ridge National Laboratory Courtney Slack, a Christine Mirzayan Science and Technol- Early information derived from radiation-induced ogy Policy Graduate Fellow, who provided additional valu- mutations in mice able assistance to NRC staff. We thank Dr. Evan Douple for pulling us in and holding R. Chakraborty, Ph.D. us together. His wise and patient counsel along with his University of Texas School of Public Health gentle encouragement, when needed, kept the committee Mini- and microsatellite mutations and their possible focused on its charge. relevance for genetic risk estimation Finally, special thanks are due to Dr. Rick Jostes, the study director. His scientific expertise, persistence, equanim- Allan Balmain, Ph.D. ity, and organizational skills were essential to our staying University of California, San Francisco the course. High- and low-penetrance genes involved in cancer incidence RICHARD MONSON, Chairman

OCR for page R1
Units Used to Express Radiation Dose Radiation exposures are measured in terms of the quan- that differs from the quality factor and the radiation weight- tity absorbed dose, which equals the ratio of energy imparted ing factor, is employed in these computations. The unit to the mass of the exposed body or organ. The unit of ab- sievert is likewise used with this quantity. sorbed dose is joules per kilogram (J/kg). For convenience Whenever the nature of the quantity is apparent from the this unit has been given the special name gray (Gy). context, the term dose is used equally in this report for ab- Ionizing radiation can consist of electromagnetic radia- sorbed dose, equivalent dose, effective dose, and weighted tion, such as X-rays or gamma rays (γ-rays), or of subatomic dose. With regard to risk assessment, reference is usually to particles, such as protons, neutrons, and α-particles. X- and the equivalent dose to specified organs or to the effective γ-rays are said to be sparsely ionizing, because they produce dose. The unit sievert is then used, although absorbed dose fast electrons, which cause only a few dozen ionizations and equivalent dose are equal for low-LET radiation. In ex- when they traverse a cell. Because the rate of energy transfer perimental radiation biology and radiotherapy, exact speci- is called linear energy transfer (LET), they are also termed fication of absorbed dose is required and the dose values are low-LET radiation; low-LET radiations are the subject of this frequently larger than in radiation protection considerations. report. In contrast, the heavier particles are termed high-LET With reference to those fields, therefore, use is made of ab- radiations because they transfer more energy per unit length sorbed dose and the unit is gray. as they traverse the cell. The Public Summary refers to radiation protection, and Since the high-LET radiations are capable of causing the dose therefore is given as sieverts throughout that chap- more damage per unit absorbed dose, a weighted quantity, ter (for a more complete description of the various dose quan- equivalent dose, or its average over all organs, effective dose, tities and units used in this report, see the Glossary and the is used for radiation protection purposes. For low-LET ra- table below). diation, equivalent dose equals absorbed dose. For high-LET radiation—such as neutrons, α-particles, or heavier ion par- ticles—equivalent dose or effective dose equals the absorbed TABLE 1 Units of Dose dose multiplied by a factor, the quality factor or the radia- tion weighting factor (see Glossary), to account for their in- Unita Symbol Conversion Factors creased effectiveness. Since the weighting factor for radia- tion quality is dimensionless, the unit of equivalent dose is Becquerel (SI) Bq 1 disintegration/s = 2.7 × 10–11 Ci also joules per kilogram. However, to avoid confusion be- Curie Ci 3.7 × 1010 disintegrations/s = 3.7 × 1010 Bq Gray (SI) Gy 1 J/kg = 100 rads tween the two dose quantities, the special name sievert (Sv) Rad rad 0.01 Gy = 100 erg/g has been introduced for use with equivalent dose and effec- Sievert (SI) Sv 1 J/kg = 100 rem tive dose. Rem rem 0.01 Sv Although the BEIR VII report is about low-LET radia- tion, the committee has had to consider information derived NOTE: Equivalent dose equals absorbed dose times Q (quality factor). Gray from complex exposures—especially from atomic bomb ra- is the special name of the unit (J/kg) to be used with absorbed dose; sievert is the special name of the unit (J/kg) to be used with equivalent dose. diation—that include a high-LET contribution in addition to aInternational low-LET radiation. A weighted dose, with a weight factor Units are designated SI. xi

OCR for page R1

OCR for page R1
Contents UNITS USED TO EXPRESS RADIATION DOSE xi PUBLIC SUMMARY 1 Introduction, 1 How Ionizing Radiation Was Discovered, 1 How Ionizing Radiation Is Detected, 2 Units Used to Describe Radiation Dose, 2 What Is Meant by Low Doses of Ionizing Radiation, 2 Exposure from Natural Background Radiation, 3 Contribution of Man-Made Radiation to Public Exposure, 3 Scenarios Illustrating How People Might Be Exposed to Ionizing Radiation above Background Levels, 4 Evidence for Adverse Health Effects Such as Cancer and Hereditary Disease, 6 The BEIR VII Risk Models, 6 Research Reviewed by the Committee, 9 Conclusions, 10 EXECUTIVE SUMMARY 11 Introduction, 11 Evidence from Biology, 11 Estimation of Heritable Genetic Effects of Radiation in Human Populations, 12 Evidence from Epidemiology, 12 Integration of Biology and Epidemiology, 14 Estimating Cancer Risks, 14 Conclusion, 15 Recommended Research Needs, 15 1 BACKGROUND INFORMATION 19 Physical Aspects of Radiation, 19 Chemical Aspects of Radiation, 29 Molecular Mechanisms of DNA Repair, 32 Summary, 39 ANNEX 1A: Ionizing Radiation and Oxidative Damage—A Viewpoint from Saccharomyces cerevisiae, 40 xiii

OCR for page R1
xiv CONTENTS 2 MOLECULAR AND CELLULAR RESPONSES TO IONIZING RADIATION 43 General Aspects of Dose-Response Relationships, 43 Induction of Chromosome Aberrations, 45 Induction of Gene Mutations in Somatic Cells, 46 Radiation-Induced Genomic Instability, 47 Cell Cycle Effects, 49 Adaptive Response, 50 Bystander Effects, 53 Hyper-Radiation Sensitivity at Low Doses, 55 Observed Dose-Response Relationships at Low Doses, 57 Summary, 62 3 RADIATION-INDUCED CANCER: MECHANISMS, QUANTITATIVE EXPERIMENTAL STUDIES, AND THE ROLE OF GENETIC FACTORS 65 Introduction, 65 Mechanisms of Tumorigenesis, 66 Radiation-Induced Genomic Instability in Radiation Tumorigenesis, 70 Quantitative Studies in Experimental Tumorigenesis, 73 Genetic Susceptibility to Radiation-Induced Cancer, 79 Summary, 89 4 HERITABLE GENETIC EFFECTS OF RADIATION IN HUMAN POPULATIONS 91 Introduction and Brief History, 91 General Framework, 92 Genetic Diseases, 92 Risk Estimation Methods, 93 Recent Advances with Respect to the Three Quantities Used with the DD Method of Risk Estimation, 94 The Doubling Dose Estimate, 101 Mutation Component of Genetic Diseases, 101 MC Estimation for Chronic Multifactorial Disease, 105 Other Potentially Relevant Data, 113 Risk Estimation, 114 ANNEX 4A: Models of Inheritance of Multifactorial Diseases in the Population, 120 ANNEX 4B: The Doubling Dose, 122 ANNEX 4C: Assumptions and Specifications of the Finite-Locus Threshold Model, 124 ANNEX 4D: Differences Between Spontaneous Disease-Causing Mutations in Humans and Radiation-Induced Mutations in Experimental Systems, 124 ANNEX 4E: Criteria Used to Assign Human Genes to One of Three Groups from the Standpoint of the Recoverability of Induced Mutations in Live Births, 125 ANNEX 4F: Radiation Studies with Expanded Simple Tandem Repeat Loci in the Mouse and Minisatellite Loci in Human Germ Cells, 125 ANNEX 4G: Doubling Doses Estimated from Genetic Data of Children of A-Bomb Survivors, 130 5 BACKGROUND FOR EPIDEMIOLOGIC METHODS 132 Introduction, 132 Collection of Epidemiologic Data, 133 Analysis of Epidemiologic Data, 136 Interpretation of Epidemiologic Data, 139

OCR for page R1
CONTENTS xv 6 ATOMIC BOMB SURVIVOR STUDIES 141 Introduction, 141 Description of the Cohort, 142 Statistical Methods, 143 All Solid Cancers, 144 Site-Specific Cancers, 147 Cancers Resulting from Exposure In Utero, 151 Benign Neoplasms, 151 Nonneoplastic Disease, 152 Life Shortening, 153 Summary, 154 7 MEDICAL RADIATION STUDIES 155 Introduction, 155 Medical Uses of Radiation, 156 Evaluation of Risk for Specific Cancer Sites, 173 Discussion, 187 Summary, 187 8 OCCUPATIONAL RADIATION STUDIES 189 Introduction, 189 Nuclear Industry Workers, 190 Workers from the Mayak Facility, 201 Chernobyl Cleanup Workers, 202 Airline and Aerospace Employees, 204 Medical and Dental Occupational Exposures, 204 Summary, 205 9 ENVIRONMENTAL RADIATION STUDIES 207 Introduction, 207 Populations Living Around Nuclear Facilities, 208 Populations Exposed from Atmospheric Testing, Fallout, or Other Environmental Release of Radiation, 212 Populations Exposed from the Chernobyl Accident, 215 Populations Exposed from Natural Background, 228 Children of Adults Exposed to Radiation, 228 Exposure to Radioactive Iodine 131, 233 Discussion, 235 Summary, 237 10 INTEGRATION OF BIOLOGY AND EPIDEMIOLOGY 239 Introduction, 239 DNA Damage Response and Cancer Risk, 239 Projection of Risks Over Time, 239 The Transport of Cancer Risk Between Different Populations, 240 Form of the Dose-Response for Radiation Tumorigenesis, 245 Dose and Dose-Rate Effects on Tumor Induction, 246 Other Forms of Cellular and Animal Response to Radiation, 250 Genetic Susceptibility to Cancer, 251 Heritable Effects of Radiation, 252 Summary, 252 ANNEX 10A: Application of the Moolgavkar and Knudson Two-Stage Clonal Expansion Model to the Transport of Radiation Cancer Risk, 253 ANNEX 10B: Evidence for the Connection Between Dose Effects and Dose-Rate Effects in Animal Experiments, 254

OCR for page R1
xvi CONTENTS 11 RISK ASSESSMENT MODELS AND METHODS 259 Risk Assessment Methodology, 259 Risk Models, 261 Variables That Modify the Dose-Response Relationship, 264 12 ESTIMATING CANCER RISK 267 Introduction, 267 Data Evaluated for BEIR VII Models, 267 Measures of Risk and Choice of Cancer End Points, 268 The BEIR VII Committee’s Preferred Models, 269 Use of the Committee’s Preferred Models to Estimate Risks for the U.S. Population, 274 Quantitative Evaluation of Uncertainty in Lifetime Risks, 278 Results of Risk Calculations, 278 Uncertainties in Lifetime Risk Estimates, 284 Coherence of Models with Other Studies, 286 Summary, 290 ANNEX 12A: Previous Models for Estimating Cancer Risks from Exposure to Low Levels of Low-LET Ionizing Radiation, 291 ANNEX 12B: Committee Analyses of Data on the LSS Cohort to Develop BEIR VII Models for Estimating Cancer Risks, 296 ANNEX 12C: Details of LAR Uncertainty Analysis, 308 ANNEX 12D: Additional Examples of Lifetime Risk Estimates Based on BEIR VII Preferred Models, 310 13 SUMMARY AND RESEARCH NEEDS 313 Evidence from Biology, 313 Genetic Effects of Radiation on Human Populations, 316 Epidemiologic Studies of Populations Exposed to Ionizing Radiation, 317 Integration of Biology and Epidemiology, 321 Models for Estimating the Lifetime Risk of Cancer, 322 Conclusion, 323 APPENDIXES 325 A BASIC BIOLOGICAL AND GENETIC CONCEPTS 327 B COMMENTARY ON “RADIATION FROM MEDICAL PROCEDURES IN THE PATHOGENESIS OF CANCER AND ISCHEMIC HEART DISEASE: DOSE-RESPONSE STUDIES WITH PHYSICIANS PER 100,000 POPULATION” 329 C ISSUES RAISED BY THE INSTITUTE FOR ENERGY AND ENVIRONMENT RESEARCH (IEER) 330 D HORMESIS 332 E FIFTEEN-COUNTRY WORKERS STUDY 336 REFERENCES 337 GLOSSARY 373 COMMITTEE BIOGRAPHIES 379 INDEX 385