HEALTH EFFECTS OF EXPOSURE TO RADON:

Time for Reassessment?

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

Board on Radiation Effects Research

Commission on Life Sciences

National Research Council

NATIONAL ACADEMY PRESS
Washington, D.C.
1994



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HEALTH EFFECTS OF EXPOSURE TO RADON: Time for Reassessment? Committee on Health Effects of Exposure to Radon (BEIR VI) Board on Radiation Effects Research Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1994

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NATIONAL ACADEMY PRESS 2101 Constitution Ave., 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 Sciences, the National Academy of Engineering, and the Institute of Medicine. The National Academy of Sciences is a private, non-profit, 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 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. 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 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 Alberts and Dr. Robert M. White are chairman and vice chairman, respectively, of the National Research Council. This project was prepared under grant #X820576-01-0 between the National Academy of Sciences and the Environmental Protection Agency. Library of Congress Catalog Card No. 94-66478 International Standard Book No 0-309-05087-1 Copies of this book may be obtained from National Academy Press 2101 Constitution Avenue, N.W. Box 285 Washington, D.C. 20055 (800) 624-6242; (202) 334-3313 B-453 Copyright 1994 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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Committee on Health Risks of Exposure to Radon (BEIR VI) JONATHAN M. SAMET (Chairman), University of New Mexico, Albuquerque, New Mexico ETHEL S. GILBERT, Battelle, Pacific Northwest Laboratories, Richland, Washington ERIC J. HALL, Columbia University, New York, New York WARREN K. SINCLAIR, National Council on Radiation Protection and Measurements (ret.), Bethesda, Maryland National Research Council Staff EVAN B. DOUPLE, Study Director MAURITA DOW-MASSEY, Project Assistant DORIS E. TAYLOR, Administrative Assistant NORMAN GROSSBLATT, Editor Sponsor’s Project Officer SUSAN CONRATH, Environmental Protection Agency

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Board on Radiation Effects Research WARREN K. SINCLAIR (Chairman), National Council on Radiation Protection and Measurements (ret.), Bethesda, Maryland DOUGLAS GRAHN, Argonne National Laboratory (ret.), Madison, Indiana ERIC J. HALL, Columbia University, New York, New York MAUREEN M. HENDERSON, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington LEONARD S. LERMAN, Massachusetts Institute of Technology, Cambridge, Massachusetts JACK B. LITTLE, Harvard University, Cambridge, Massachusetts JONATHAN M. SAMET, University of New Mexico, Albuquerque, New Mexico THOMAS S. TENFORDE, Battelle Pacific Northwest Laboratories, Richland, Washington H. RODNEY WITHERS, UCLA Medical Center, Los Angeles, California (member as of August 1993)

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National Research Council Staff CHARLES W. EDINGTON, Director, until May 15, 1993 JOHN D. ZIMBRICK, Director, as of July 6, 1993 EVAN B. DOUPLE, Senior Program Officer LARRY H. TOBUREN, Senior Program Officer as of February 1, 1993 CATHERINE S. BERKLEY, Administrative Associate MAURITA DOW-MASSEY, Project Assistant DORIS E. TAYLOR, Administrative Assistant

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Commission on Life Sciences THOMAS D. POLLARD (Chairman), Johns Hopkins Medical School, Baltimore, Maryland BRUCE N. AMES, University of California, Berkeley, California JOHN C. BAILAR III, McGill University, Montreal, Canada J. MICHAEL BISHOP, University of California Medical Center, San Francisco, California JOHN E. BURRIS, Marine Biological Laboratory, Woods Hole, Massachusetts MICHAEL T. CLEGG, University of California, Riverside, California GLENN A. CROSBY, Washington State University, Pullman, Washington LEROY E. HOOD, University of Washington, Seattle, Washington MARIAN E. KOSHLAND, University of California, Berkeley, California RICHARD E. LENSKI, Michigan State University, East Lansing, Michigan EMIL A. PFITZER, Hoffmann-La Roche Inc., Nutley, New Jersey MALCOLM C. PIKE, University of Southern California School of Medicine, Los Angeles, California

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HENRY C. PITOT III, University of Wisconsin, Madison, Wisconsin PAUL G. RISSER, Miami University, Oxford, Ohio JONATHAN M. SAMET, University of New Mexico, Albuquerque, New Mexico HAROLD M. SCHMECK, JR., Armonk, New York CARLA J. SHATZ, University of California, Berkeley, California SUSAN S. TAYLOR, University of California San Diego, La Jolla, California P. ROY VAGELOS, Merck & Co., Inc., Whitehouse Station, New Jersey JOHN L. VANDEBERG, Southwest Foundation for Biomedical Research, San Antonio, Texas TORSTEN N. WIESEL, Rockefeller University, New York, New York National Research Council Staff PAUL GILMAN, Executive Director ALVIN G. LAZEN, Associate Executive Director

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Preface The National Research Council Committee on Health Risks of Exposure to Radon (BEIR VI), in the Board on Radiation Effects Research (BRER) of the Commission on Life Sciences (CLS), was formed in August 1992 in response to a request from the Environmental Protection Agency (EPA) that a Research Council committee consider recently published data and soon-to-be-completed studies concerning the risk associated with human exposure to radon. The BEIR series of reports focuses on biological effects of ionizing radiation. The Research Council report Health Risks of Radon and Other Internally Deposited Alpha-Emitters: BEIR IV published in 1988, had reviewed the health effects of radon and offered a risk model based on data from four studies of underground miners. Using data from a few studies, it estimated the combined effects of radon and cigarette-smoking on the production of lung cancer. The Research Council report Comparative Dosimetry of Radon in Mines and Homes, issued in 1991, provided more complete coverage of radon dosimetry than had been accomplished by the BEIR IV committee. EPA has placed a high priority on a re-evaluation of 

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risks to ensure that new data, including data on exposures in homes and schools, can be expeditiously incorporated into risk evaluations. New information on the relationship between radon exposure and cigarette-smoking also needs to be considered, as well as the potential effect of arsenic in mines. The Research Council established a committee of four members with expertise in radiation biology, radiation physics and dosimetry, epidemiology and biostatistics, and pulmonary medicine. General guidance was provided by BRER. EPA had asked for assistance in two phases. In Phase I, the committee was to collect and evaluate data as studies were completed and to determine whether sufficient data had become available since the publication of BEIR IV and Comparative Dosimetry of Radon in Mines and Homes to warrant a full-scale analysis (Phase II). The present report is a summary of the committee's findings in Phase I, including a recommendation regarding the feasibility and likely contributions of a Phase II study. The committee members were asked specifically to do the following: Familiarize themselves with studies completed since the evaluations of data by committees of BRER in 1988 and 1991. Inform themselves of the nature and purpose of current studies of underground miners and the general population in the United States and abroad. Identify differences and similarities in results among studies analyzed previously and those recently published. Identify issues in need of analysis in a full-scale study. Establish liaison with international groups that coordinate various radon studies. Assess the evaluations of data performed by the international coordinating groups to determine whether these are sufficiently

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definitive to obviate further evaluation by a Research Council group. Advise EPA on whether the accumulation of data from current investigations from throughout the world makes it feasible and advisable to perform detailed re-analyses of two critical issues during a second phase of study. The two issues are models of carcinogenesis associated with combined exposure to radon and cigarette-smoking and comparisons of exposure to radon in mines and in homes. If Phase II is feasible and advisable, plan the organization and approach for the full-scale committee and study. Prepare a report summarizing the committee's findings during the first phase and recording its recommendations for work, if any is feasible and desirable, in the second phase. The committee completed all the above tasks. It held five meetings-two in Washington, D.C., one in Albuquerque, and two in Denver-and engaged in conference calls. Two of the meetings were workshops during which outside experts were invited to comment on current scientific knowledge and to present the results of their research. The first workshop focused on radon dosimetry and included sessions devoted to respiratory tract models, aerosols, deposition and clearance, dosimetry, cell proliferation, and cells at risk. The second focused on molecular and cellular radiobiology and included sessions devoted to radiation dose and dose rate, interactions between chemicals and radiation, molecular and cellular signatures of exposure, and biologic models. The committee also received status reports from the principal investigators z of current case-control epidemiologic studies addressing the effects of radon in homes. This report is organized according to the major elements of the

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committee's analysis. After an executive summary containing recommendations, an introduction (Chapter 1) provides the background of the committee's activities and an overview of the radon problem. The three major elements follow as chapters titled ''Radiation Biology and Carcinogenesis," "Exposure-Dose Relations," and "Epidemiologic Investigations." Each of those chapters summarizes the information that has emerged since BEIR IV and its companion report on comparative dosimetry, reviews current studies, projects what information is likely to become available during the next 2 years for a Phase II committee working on a BEIR VI report, and concludes with recommendations as to what a Phase II committee should be able to do with this information; they substantiate the committee's recommendation regarding the feasibility of a Phase II study and a BEIR VI report. The committee acknowledges with thanks the scientific input provided by invited participants who gave freely of their data and findings and were of great help in clarifying some of the scientific issues under study. The committee is especially grateful to Marshall Anderson, William Bair, William Bennett, Bruce Boecker, John Boice, David Brenner, Antone Brooks, Yung Sun Cheng, Fred Cross, Greg Finch, William Griffith, Frank Guilliland, Raymond Guilmette, Thomas Hei, Philip Hopke, Anthony James, David James, Neil Johnson, John Lechner, Jay Lubin, Suresh Moolgavkar, David Swift, Margaret Terzaghi-Howe, and Hsu-Chi Yeh. Michael Alavanja, Sarah Darby, L. Kreienbrock, J. Lyon, Richard McGregor, William Nicholson, Goran Pershagen, Dale Sandler, Janet Schoenberg, Heather Stockwell, Jan Stolwijk, Margot Tirmarche, and H.-Erich Wichmann are thanked for contributing information on their case-control studies in progress. We also thank Susan Conrath, Neal Nelson, Jerome Puskin, and Anita Schmidt of EPA and Marvin Frazier, Curtis Olsen, and Susan

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Rose of the Department of Energy for information on their radon programs. Finally, the committee thanks Doris E. Taylor, Maurita DowMassey, and Edward Patte for their assistance with administrative details and in preparing drafts of this report. Jonathan M. Samet, Chairman

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Contents EXECUTIVE SUMMARY   1 1   INTRODUCTION   11 2   RADIATION BIOLOGY AND CARCINOGENESIS   17     Introduction,   17     Range and Track Structure of Particles Emitted by Radon Progeny,   18     Radiation Biology of -Particle Irradiation,   20     Cell Lethality,   21     Mutation in Cultured Cells,   21     Oncogenic Transformation in Vitro,   24     Comparison of Effects In Vivo and In Vitro,   28     Carcinogenesis in Laboratory Animals,   29     RBE Versus LET,   30

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    Dose-Rate Effects and Implications for Risk Estimates,   32     Mechanisms of Carcinogenesis,   35     Markers of Exposure,   39     Summary and Recommendations,   41 3   EXPOSURE-DOSE RELATIONS   43     Status of Studies,   43     Summary and Recommendations,   49 4   EPIDEMIOLOGIC INVESTIGATIONS   51     Studies of Miners,   51     Overview,   51     Cohorts of Miners,   52     Lung Cancer in Pooled Analysis of 11 Cohorts,   54     Assessment of Uncertainty in Lifetime Risk Estimates,   58     Nonrespiratory Cancers,   59     Nonmalignant Respiratory Diseases,   61     Studies of Lung Cancer in the General Environment,   61     Overview,   61     Case-Control Studies,   62     Status,   63     Problems and Limitations,   66

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    Ecologic Studies,   69     Status,   69     Problems and Limitations,   70     Radon-Induced Cancers Other than Lung Cancer,   71     Summary and Recommendations,   72     Studies of Miners,   73     Studies of Lung Cancer in the General Environment,   74     LITERATURE CITED   75     INFORMATION ON COMMITTEE MEMBERS   93

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HEALTH EFFECTS OF EXPOSURE TO RADON: Time for Reassessment?

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