HEALTH EFFECTS OF EXPOSURE TO RADON

BEIR VI

Committee on Health Risks of Exposure to Radon (BEIR VI)

Board on Radiation Effects Research

Commission on Life Sciences

National Research Council

NATIONAL ACADEMY PRESS
Washington, D.C.
1999



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Health Effects of Exposure to Radon: BEIR VI HEALTH EFFECTS OF EXPOSURE TO RADON BEIR VI Committee on Health Risks of Exposure to Radon (BEIR VI) Board on Radiation Effects Research Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1999

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Health Effects of Exposure to Radon: BEIR VI NATIONAL ACADEMY PRESS 2101 Constitution Avenue, NW 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 to appropriate balance. This report was prepared under Grant No. X820576-01-0 between the National Academy of Sciences and the Environmental Protection Agency. Health Risks of Exposure to Radon: BEIR VI is available for sale from the National Academy Press, 2101 Constitution Avenue, N.W., Lock Box 285, Washington, DC, 20055. Call 800-624-6242 or 202-334-3938 (Washington Metropolitan Area); Internet, http://www.nap.edu Library of Congress Cataloging-in-Publication Data Health effects of exposure to radon / Committee on Health Risks of Exposure to Radon, Board on Radiation Effects Research, Commission on Life Sciences, National Research Council. p. cm. — (BEIR ; 6) Includes bibliographical references and index. 1. Radon—Health aspects. 2. Radon—Toxicology. 3. Radon—Physiological effect. 4. Radiation carcinogenesis. 5. Indoor air pollution—Health aspects. 6. Health risk assessment. I. National Research Council (U.S.) Committee on Health Risks of Exposure to Radon. II. Series: BEIR (Series) ; 6. RA1247.R33.H425 1998 98-25503 363.17'99—ddc21 International Standard Book Number 0-309-05645-4 Copyright 1999 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 Radon: BEIR VI COMMITTEE ON HEALTH RISKS OF EXPOSURE TO RADON (BEIR VI) JONATHAN M. SAMET (Chairman), Department of Epidemiology, The Johns Hopkins University, Baltimore, Maryland DAVID BRENNER, College of Physicians and Surgeons, Columbia University, New York ANTONE L. BROOKS, Washington State University at Tri-Cities, Richland, Washington WILLIAM H ELLETT, National Research Council (ret.), Crofton, Maryland ETHEL S. GILBERT, Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland DUDLEY T. GOODHEAD, Medical Research Council, Oxfordshire, England ERIC J. HALL, College of Physicians and Surgeons, Columbia University, New York PHILIP K. HOPKE, Department of Chemistry, Clarkson University, Potsdam, New York DANIEL KREWSKI, Faculty of Medicine, University of Ottawa, and Health Protection Branch, Health Canada, Ottawa, Canada JAY H. LUBIN, Biostatistics Branch, National Cancer Institute, Bethesda, Maryland ROGER O. McCLELLAN, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina PAUL L. ZIEMER, School of Health Sciences, Purdue University, West Lafayette, Indiana NATIONAL RESEARCH COUNCIL STAFF EVAN B. DOUPLE, Study Director; Director, Board on Radiation Effects Research (as of April 1997) JOHN D. ZIMBRICK, Director, Board on Radiation Effects Research (through December 1996) AMY NOEL O'HARA, Project Assistant (through November 10, 1997) CATHERINE S. BERKLEY, Administrative Associate DORIS E. TAYLOR, Administrative Assistant NORMAN GROSSBLATT, Editor SPONSOR'S PROJECT OFFICER SUSAN CONRATH, U.S. Environmental Protection Agency ANITA SCHMIDT, U.S. Environmental Protection Agency

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Health Effects of Exposure to Radon: BEIR VI BOARD ON RADIATION EFFECTS RESEARCH JOHN B. LITTLE (Chairman), Harvard University, Cambridge, Massachusetts VALERIE BERAL, University of Oxford, Oxford, England MAURICE S. FOX, Massachusetts Institute of Technology, Cambridge, Massachusetts R. J. MICHAEL FRY, Oak Ridge National Laboratory (ret.), 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, 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 EVAN B. DOUPLE, Director (as of April 1997) JOHN D. ZIMBRICK, Director (through December 31, 1996) STEVEN L. SIMON, Senior Program Officer RICK JOSTES, Senior Program Officer CATHERINE S. BERKLEY, Administrative Associate DORIS E. TAYLOR, Administrative Assistant AMY NOEL O'HARA, Project Assistant (through November 10, 1997) KAREN M. BRYANT, Project Assistant PEGGY Y. JOHNSON, Project Assistant

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Health Effects of Exposure to Radon: BEIR VI COMMISSION ON LIFE SCIENCES THOMAS D. POLLARD (Chairman), Salk Institute for Biological Studies, La Jolla, California FREDERICK R. ANDERSON, Cadwalader, Wickersham & Taft, Washington, D.C. JOHN C. BAILAR III, University of Chicago, Chicago, Illinois PAUL BERG, Stanford University, Stanford, California JOANNA BURGER, Rutgers University, Piscataway, New Jersey SHARON L. DUNWOODY, University of Wisconsin, Madison, Wisconsin JOHN L. EMMERSON, Indianapolis, Indiana NEAL L. FIRST, 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-Farber Cancer Institute, Boston, Massachusetts THOMAS E. LOVEJOY, Smithsonian Institution, Washington, D.C. DONALD R. MATTISON, Graduate School of Public Health, 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

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Health Effects of Exposure to Radon: BEIR VI 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 the 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 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 advising 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 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 Radon: BEIR VI Preface Nearly a decade has passed since the fourth in a series of studies called Biological Effects of Ionizing Radiation (BEIR) assessed the risks posed by exposure to radon and other alpha emitters in 1988. Radon, a gas emitted into homes from the soil, from water and from building materials, becomes trapped in homes. Its radioactive daughters, the progeny of radioactive decay, are inhaled into human lungs, where further decay results in the exposure of lung cells to densely ionizing alpha particles. On the basis of considerable experience gained by studying health effects in uranium and other miners who worked in radon-rich environments, the radioactive radon progeny were identified as a cause of lung-cancer. It has not been clear whether radon poses a similar risk of causing lung-cancer in men, women, and children exposed at generally lower levels found in homes, but homeowners are concerned about this potential risk, and the Environmental Protection Agency (EPA) suggests "action levels," concentrations to which citizens are encouraged to reduce their levels of exposure. Motivated by the ubiquitous exposure of the general population to radon and the continued concern about the risks of exposure to this natural radioactive carcinogen, EPA sought the advice of the National Academy of Sciences and the National Research Council in re-examining the approaches to assessing the lung-cancer risk associated with radon concentrations in the domestic environment. As requested by EPA, the National Research Council first conducted a scoping study; in its 1994 report The Health Effects of Exposure to Radon: Time for Reassessment?, the BEIR VI Phase I committee concluded that sufficient and appropriate new evidence had become available since the 1989 BEIR IV report to justify a new National Research Council BEIR VI study. Consequently, the

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Health Effects of Exposure to Radon: BEIR VI BEIR VI committee, consisting of 13 scientists with the expertise required to explore EPA's charge, was formed in 1994 to reexamine the risk of health effects posed by exposure to radon in homes. The report that follows includes 4 chapters and 7 appendixes. The chapters provide the committee's principal findings; supporting analyses and other related evidence are presented in the appendixes. After an introduction to the radon problem in chapter 1, the biologic evidence on mechanisms of radon-related lung-cancer is reviewed in chapter 2, which summarizes information on issues identified by the committee as critical to assessing lung-cancer risk from radon exposure. Chapter 3 presents the committee's risk models and 3 major risk projections, provides the rationale for the committee's modeling decisions, describes the committee's preferred risk models and the projections of lung-cancer risk resulting from their use, and addresses the issues related to uncertainty in the risk projections. Chapter 4 reviews the evidence on health effects other than lung-cancer that result from exposure to radon progeny. The appendixes support the committee's findings and should be consulted by readers who want in-depth coverage of specific issues. Appendix A is devoted to previously used risk models, the committee's methods and approach to risk modeling, and the details of the uncertainty considerations and analyses. Radon dosimetry is discussed in appendix B, which updates a 1991 National Research Council report on this subject. The dominant cause of lung-cancer in the United States and many other countries is tobacco-smoking; appendix C provides additional information on the risks of lung-cancer in relation to smoking and reviews the available data on the combined effects of smoking and exposure to radon and its progeny. Appendixes D, E, and F address the information available from epidemiologic studies on underground miners. Appendix D summarizes the characteristics and designs of the miner studies. Appendix E and its annexes review the details of the exposures in individual miner studies and provide the proceedings of a workshop on exposure estimation. Appendix F addresses exposures to agents other than radon—such as diesel exhaust, silica, and arsenic—which might be relevant to estimating lung-cancer risk posed by radon. The findings of studies—principally ecologic or case-control epidemiologic studies conducted to estimate directly the risk posed by radon exposure in homes—are described in appendix G. The findings of several individual studies and combined analyses of the case-control studies are summarized. Finally, a compilation of the literature cited in the report and a glossary of technical terms used in the report follows appendix G. ACKNOWLEDGMENTS In the course of doing its work, the committee held several meetings, including a meeting in which the scientific community and other interested groups were

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Health Effects of Exposure to Radon: BEIR VI invited to present suggestions regarding the problem. Other information-gathering meetings were held in which scientists with specific expertise were invited to discuss the results of their work. Several workshops were held in which the committee focused on particular aspects of the radon problem. The committee is grateful to participants in a January 1996 workshop, in which over 30 scientists discussed findings of work relevant to the shape of the dose-response curve at low doses of radiation with densely deposited energy applicable to the alpha particles emitted by radon and its progeny. The results of that workshop, which was sponsored by the Department of Energy's Office of Health and Environmental Research, were useful to the committee in selecting a risk-assessment model. The committee is appreciative to the many scientists who contributed directly or indirectly to the work of the BEIR VI committee. Seven persons and groups deserve special recognition and thanks. First, the committee is indebted to the principal investigators (PIs) and other scientists who directed and analyzed the various cohort studies of miners and the case-control studies of lung-cancer and radiation in the general population. Those scientists willingly and graciously provided their data to the committee and enabled the committee to apply analytical techniques to original data in order to derive its models and its risk estimates. For the miner studies, the scientists included Shu-Xiang Yao, Xiang-Zhen Xuan, and Jay H. Lubin (Chinese tin miners), Emil Kunz and Ladislav Tomásek (Czechoslovakian, now the Czech Republic, Uranium miners), Geoffrey Howe (Beaver-lodge, Canada and Port Radium, Canada uranium miners), Howard I. Morrison (Newfoundland, Canada fluorspar miners), Robert A. Kusiak and Jan Muller (Ontario, Canada uranium miners), Margot Tirmarche (French uranium miners), Alistair Woodward (South Australian uranium miners), Edward P. Radford and Christer Edling (Swedish iron miners), Richard W. Hornung (Colorado, U.S.A. uranium miners), and Jonathan M. Samet (New Mexico, U.S.A. uranium miners). Second, the committee sponsored a workshop on exposures of miners to radon progeny. The following persons, knowledgeable about the history of the mining industry with experience in geology or mine and ventilation engineering, were invited to the workshop and made contributions that were much appreciated: William Chenoweth, James Cleveland, Andreas George, and Douglas Chambers. During the workshop, Daniel Stram and Duncan Thomas provided advice to the committee regarding quantification of the measurement errors associated with the mine exposures. Third, the committee expresses its thanks to Anthony James, who provided computational analyses of doses to lung cells resulting from radon and its progeny. Fourth, the committee thanks Susan Rose of the Department of Energy for inviting the BEIR VI chair and study director to participate in meetings of the PIs of the case-control studies in Europe and North America in which plans for pooling of data and joint analyses were discussed. Fifth, three scientists from Health Canada provided valuable computational analyses and assisted committee members in the development and application of

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Health Effects of Exposure to Radon: BEIR VI the risk assessment: Shesh N. Rai, Yong Wang, and Jan M. Zielinski. Their contributions were important in the development of chapter 3 and appendix A. Sixth, the committee is especially grateful to Rosalyn Yalow, an original committee member whose health prohibited her from serving as a final author of the study. Dr. Yalow was especially effective in insuring that the committee not overlook the influence of cigarette-smoking on the lung-cancer problem. Seventh, this report has been reviewed by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the authors and the National Research Council in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The content of the review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report: Gregg Claycamp (University of Pittsburgh School of Public Health), Merril Eisenbud (deceased), Robert Forster (University of Pennsylvania School of Medicine), Naomi Harley (New York University Medical Center), Werner Hofmann (University of Salzburg), Maureen Henderson (University of Washington), Richard Hornung (University of Cincinnati), Donald Mattison (University of Pittsburgh School of Public Health), Suresh Moolgavkar (University of Washington), Lincoln Moses (Stanford University), Louise Ryan (Harvard University School of Public Health), and Duncan Thomas (University of Southern California). Although the individuals listed above have provided many constructive comments and suggestions, responsibility for the final content of this report rests solely with the authoring committee and the National Research Council. The committee appreciates the assistance of the Board on Radiation Effects Research (BRER) staff who supported the committee's work, especially Doris Taylor for her assistance with meeting and travel arrangements and Amy Noel O'Hara and Dennis Gleeson, Jr., for their attention to the details of manuscript preparation. The BEIR VI committee has faced many challenges in preparing this report. Committee members are hopeful that the report will meet the needs of the EPA as it considers risk management strategies for indoor radon and also will be informative to the public as homeowners make decisions about testing for radon and lowering radon concentrations in their homes. JONATHAN SAMET, M.D. CHAIR, COMMITTEE ON HEALTH EFFECTS OF EXPOSURE TO RADON, (BEIR VI)

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Health Effects of Exposure to Radon: BEIR VI Contents     Public Summary   1     Executive Summary   4     Introduction   4     The Mechanistic Basis of Radon-Induced Lung-Cancer   5     The BEIR VI Risk Models   7     Risk Assessment   8     Lung Dosimetry of Radon Progeny   9     Extrapolation of Risks at Higher Exposures to Lower Exposures   9     Exposure Rate   9     Combined Effect of Smoking and Radon   10     Risks for Women   10     Risks Associated with Exposures in Childhood   10     Characterization of Radon Risks   10     Radon-Attributable Risks   11     Uncertainty Considerations   16     Effects of Radon Exposure Other Than Lung-Cancer   18     Conclusions   18 1   Introduction   20     Radon and Lung-Cancer: an Overview   20     Prior Reports on the Risk Associated With Radon   24     Population Exposure to Radon   27     The Committee's Approach   28     Critical Issues   31     Extrapolation from Higher to Lower Exposures   31

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Health Effects of Exposure to Radon: BEIR VI     Extrapolation from Higher to Lower Exposure Rates   32     Interactions of Radon Progeny with Other Agents   32     Susceptibility   33     Links Between Biologic Evidence and Risk Models   33     Signatures of Radon Effects   33     Overview of Committee Risk Assessment   34 2   The Mechanistic Basis of Radon-Induced Lung-Cancer   36     Introduction   36     Radiation and Oncogenes   38     Tumor-Suppressor Genes   39     Genomic Instability   40     Individual and Genetic Susceptibility   41     Cell-Cycle Effects   44     Apoptosis   45     Radiation-Induced Perturbations of Cellular Proliferation   45     Cells at Risk   46     Target Size   48     The Special Nature of Biologic Damage Induced by Alpha Particles   49     Biologic Effects of Low Exposure Levels to Alpha Particles   56     Biologic Effects of Alpha Particles at Low Exposure Rates   58     Interactions Between Lung Carcinogens   62     The Dosimetric Approach to Radon Risk Estimation   63     Mechanistic Considerations in Assessing Risks Associated with Radon   64     Biologically-Based Risk Models   64     Extrapolation From High to Low Radon-Progeny Exposures   65     Effect of Changing Exposure Rate   67     Interaction of Radon Progeny with Other Agents   67     Biologic Signatures of Alpha-Particle Cancers   68     Individual Susceptibility   68 3   Models and Risk Projections   69     Introduction   69     Risk-Estimation Approaches   70     Dosimetric Approach   70     Biologically Motivated Approach   70     Empirical Approach   71     Rationale for the Committee's Chosen Method for Radon Risk Estimation   72     Previous Models   74     BEIR VI Risk Model for Lung-Cancer in Miners   76     Introduction   76     Sources of Data   76

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Health Effects of Exposure to Radon: BEIR VI     Analysis of Pooled Data from Different Studies   78     Model Based on Full Data Set   80     Model Based on Exposure-Restricted Data   81     Coherence of Evidence from Miners and from the General Population   84     BEIR VI Risk Assessment for Lung-Cancer in the General Population   85     Introduction   85     Measures of Risk   91     Relative-Risk Estimates   92     Population-Risk Estimates   93     Sources of Uncertainty   100     Uncertainties in Parameter Estimates Derived from Underground-Miner Data   101     Uncertainties in Specification of the Lung-Cancer Exposure-Response Model and Its Application to Residential Exposure of the General U.S. Population   103     Uncertainty Analysis   104     Comparisons with BEIR IV   110     BEIR IV and BEIR VI Risk Models   110     Summary and Conclusions   113 4   Health Effects of Radon Progeny on Non-Lung-Cancer Outcomes   117     Doses to Organs Other Than Lung   118     Nonmalignant Respiratory Diseases   119     Malignancies Other Than Lung-Cancer   120     Studies of Underground Miners   121     Studies of the General Population   124     Reproductive Outcomes   127     Conclusions   127     Appendixes     A   Risk Modeling and Uncertainty Analysis   129 B   Comparative Dosimetry   176 C   Tobacco-Smoking and Its Interaction with Radon   224 D   Miner Studies   254 E   Exposures of Miners to Radon Progeny   291     Annex 1: Exposures to Miner Cohorts: Review of Estimates for the Studies   306     Annex 2: Workshop on Uncertainty in Estimating Exposures to Radon Progeny in Studies of Underground Miners   331

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Health Effects of Exposure to Radon: BEIR VI F   Exposures Other Than Radon in Underground Mines   344 G   Epidemiologic Studies in the Indoor Environment   356     References   430     Glossary   472     Committee Biographies   482     Index   487