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OCR for page R1
HEALTH EFFECIS OF
E(POSURE ~
LOW LEVEIS OF
IONIZING
RADIATION
BEIR V
Committee on the Biological Effects
of Ionizing Radiations
Board on Radiation Effects Research
Commission on Life Sciences
National Research Council
NATIONAL ACADEMY PRESS
Washington, D.C. 1990
OCR for page R2
National Academy Press
.
2101 Constitution Avenue, N.W. ~
Washington, D.C. 20418
NOTICE: The project that is the subject of this report was approved by the Governing Board of the
National Research Council, whose members are drawn from the councils of the National Academy of
Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the
committee responsible for the report were chosen for their special competences and with regard for
appropriate balance.
This report has been reviewed by a group other than the authors according to procedures
approved by a Report Review Committee consisting of members of the National Academy of Sciences,
the National Academy of Engineering, and the Institute of Medicine.
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. Frank Press is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National
Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its
administration and in the selection of its members, sharing with the National Academy of 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. Samuel O. Thier is
president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to
associate the broad community of science and technology with the Academy's purposes of 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. Frank Press and Dr. Robert M. White
are chairman and vice chairman, respectively, of the National Research Council.
The study summarized in this report was supported by the Oak Ridge Associated Universities,
acting for the Office of Science and Technology Policy's Committee on Interagency Radiation Research
and Policy Coordination (CIRRPC) under Purchase Order No. C-43892.
International Standard Book Number 0-309-03995-9 (paper) 0-309-03997-5 (cloth)
Library of Congress Catalog Card Number 89~4118
Copyright ~ 1990 by the National Academy of Sciences
No part of this book may be reproduced by any mechanical, photographic, or electronic process, or
in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or
otherwise copied for public or private use, without written permission from the publisher, except for
the purposes of official use by the United States Government.
Printed in the United States of America
First Printing, December 1989
Second Printing, June 1990
Third Printing, January 1991
Fourth Printing, March 1995
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COMMITTEE ON THE BIOLOGICAL
EFFECTS OF IONIZING RADIATIONS
ARTHUR C. UPTON, Chairman, Department of Environmental
Medicine, New York University Medical Center, New York, New York
DANIEL L. HARTL, Vice Chairman, Department of Genetics,
Washington University School of Medicine, St Louis, Missouri
BRUCE B. BOECKER, Inhalation Toxicology Research Institute,
Albuquerque, New Mexico
KELLY H. CLIFTON, University of Wisconsin Clinical Cancer Center,
Madison, Wisconsin
CARTER DENNISTON, Department of Genetics, University of
Wisconsin, Madison, Wisconsin
EDWARD R. EPP, Division of Radiation Biophysics, Massachusetts
General Hospital, Boston, Massachusetts
JACOB I. FABRIKANT, Donner Laboratory, Univerisity of California,
Berkeley, California
DOUGLAS GRAHN, Argonne National Laboratory, Argonne, Illinois
ERIC J. HALL, Radiological Research Laboratory, Columbia University,
New York, New York
DONALD E. HERBERT, Department of Radiology, University of South
Alabama, Mobile, Alabama
DAVID G. HOEL, National Institute of Environmental Health Science,
Research Triangle Park, North Carolina
GEOFFREY R. HOWE, National Cancer Institute of Canada, University
of Toronto, Toronto, Ontario, Canada
SEYMOUR JABLON, National Cancer Institute, Bethesda, Maryland
ANN R. KENNEDY, Department of Radiation Oncology, Hospital of the
University of Pennsylvania, Philadelphia, Pennsylvania
ALFRED G. KNUDSON, JR., Fox Chase Cancer Center, Philadelphia,
Pennsylvania
DUNCAN C. THOMAS, Department of Preventive Medicine, University
of Southern California, Los Angeles, California
DALE PRESTON, Scientific Advisor to the Committee, National Cancer
Institute, Bethesda, Maryland
. . .
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National Research Council Staff
WILLIAM H ELLE1T, Study Director, Board on Radiation Effects
Research, Commission on Life Sciences
RAYMOND D. COOPER, Senior Program Officer, Board on Radiation
ERects Research, Commission on Life Sciences
RICHARD E. MORRIS, Editor, National Academy Press
SponsoPs Project Officer
WILLIAM ~ MILLS, Oak Ridge Associated Universities
1V
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Preface
BACKGROUND
The National Research Council's committees on the Biological Effects
of Ionizing Radiations (BEIR) have prepared a series of reports to advise
the U.S. government on the health consequences of radiation exposures.
The most recent of these reports "Health Risks of Radon and Other
Internally Deposited Alpha-Emitters BEIR IV" was published in 1988.
The last BEIR report to address health effects from external sources of
penetrating electromagnetic radiation such as x rays and gamma rays was
the report by the BEIR III Committee, "The Effects on Populations of
Exposure to Low Levels of Ionizing Radiation: 1980." That report relied
heavily on the mortality experience of the Japanese A-bomb survivors from
1950 through 1974 as a basis for the risk estimates it contains. The need for
replacement of the BEIR III report became obvious when it was determined
that the long standing estimates of the radiation exposures received by the
A-bomb survivors, that had been utilized by the BEIR III Committee,
required extensive revision. Following a binational research program by
U.S. and Japanese scientists, a reassessment of A-bomb dosimetry was
largely completed in 1986 and a new program of survivor dose estimation
was initiated by the Radiation Effects Research Foundation (RERF) at
Hiroshima and Nagasaki. In addition, RERF scientists extended their
follow-up of A-bomb survivor mortality through the year 1985.
In April of 1986, the Office of Science and Technology Policy's Commit-
tee on Interagency Radiation Research and Policy Coordination (CIRRPC)
asked the National Research Council to form a new BEIR committee to
OCR for page R6
V1
PREFACE
report on the effect of ionizing radiations on the basis of the new infor-
mation that was becoming available. A purchase agreement between the
Oak Ridge Associated Universities, acting for CIRRPC, and the National
Research Council to fund the BEIR V Committee was concluded in June
of 1986.
CHARGE TO THE COMMITTEE
The new BEIR V Committee was asked by CIRRPC to conduct
a comprehensive review of the biological effects of ionizing radiations
focusing on information that had been reported since the conclusion of
the BEIR III study, and to the extent that available information permitted,
provide new estimates of the risks of genetic and somatic effects in humans
due to low-level exposures of ionizing radiation. These risk estimates
were to address both internal and external sources of radiation, and the
procedure by which these risk estimates are derived was to be documented.
The Committee was also asked to discuss the uncertainty in their risk
estimates and, where possible, quantitate these uncertainties including the
consequences of any necessary assumptions. Finally, the Committee was
asked to prepare a detailed final report of their findings in a form suitable
for making health risk assessments and calculating the probability that an
observed cancer may be due to radiation. lThe conclusions of the BEIR
IV Committee concerning alpha particle emitters were to be summarized
in this final report to an extent consistent with the BEIR V Committee's
presentation, but additional review of the scientific literature on the effects
on alpha particle radiation was not required. While the BEIR V Committee
was asked to summarize radiation risk information in a way that is useful
for formulating radiation control decisions, recommendations on standards
or guidelines for radiation protection were specifically excluded under the
terms of this study.
ORGANIZATION OF THE STUDY
To carry out the charge, the NRC appointed a committee of scientists
experienced in radiation carcinogenesis, epidemiology, radiobiology, genet-
ics, biostatistics, pathology, radiation dosimetry, radiology, mathematical
modeling, and risk assessment. The study was conducted under the general
guidance of the Board on Radiation Effects Research of the Commission
on Life Sciences.
To facilitate its work and to augment its expertise so as to encompass a
wider spectrum of scientific subjects, the Committee solicited specific con-
tributions from a number of scientific experts other than its own members.
OCR for page R7
PREFACE
. .
VII
These experts participated in the Committee's deliberations throughout the
course of its work.
The Committee held eight meetings over a period of 30 months-
seven in Washington, D.C., and one in Woods Hole, Massachusetts. The
second meeting, on March 2, and March 3, 1987 included a public meeting,
at which open discussion and contributions from interested scientists and
the public at large were invited. In addition, over a dozen meetings of
subgroups of the Committee were held to plan and carry out specific work
assignments.
The Committee organized its work according to the main objectives of
the charge and divided the study into the following categories:
.
Heritable genetic effects.
· Cellular radiobiology and carcinogenic mechanisms.
· Radiation carcinogenesis.
· Radiation effects on the fetus.
.
Radiation epidemiology and risk modeling.
The expertise of the Committee, including its invited participants, permitted
considerable overlapping of assignments among the different categories,
ensuring interaction between scientific specialists in different disciplines.
OCR for page R8
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Acknowledgments
In order to respond to the broad charge to the Committee, the work
of the Committee was assisted by a number of experts in selected scientific
disciplines. The Committee wishes to acknowledge with thanks the valuable
contributions of the Directors and Staff of the Radiation Effects Research
Foundation, Hiroshima, Japan, for providing the most current Life Span
Study data on the Japanese atomic-bomb survivors, and for new organ dose
estimates based on the revised atomic-bomb dosimetry. These records
have emerged as the most complete data base on the health effects of
low-LET radiation exposure in human populations, and continue to be
the most comprehensive that have been analyzed for purposes of risk
estimation. The analyses presented in the Committee's report were made
possible by computational programs developed at the Radiation Effects
Research Foundation; Dale Preston, who was responsible for much of their
development, served as Scientific Advisor to the Committee, and provided
invaluable aid during the course of its deliberations.
The preparation of the report required broad scientific experience in
several interrelated disciplines. In this regard, the Committee acknowledges
the special help, effort and time of a number of invited participants, and
especially Sarah C. Darby, James V. Neel, Susan Preston-Martin, Elaine
Ron, William J. Schull, Oddvar Nygaard, and Roy Shore. All of these
scientists provided scientific data, advice, and help in the preparation or
review of scientific sections of the report, and gave freely of their time and
scientific expertise. The Committee would also like to thank Dr. Alice
IX
OCR for page R10
x
ACKNOWLEDGMENTS
Stewart for meeting with the Committee's cancer risk group and providing
advance copies of the paper on the A-bomb survivors she presented at the
14th Gray Conference, Oxford, 1988.
Very special thanks are extended to Lea Arnold, Doris E. Taylor, and
Collette A. Carmi, for their administrative support and for preparation of
the many drafts of the report. Their tasks were done with speed and good
humor; they were invaluable in assisting the members of the Committee in
the completion of their work
ARTHUR UPTON, Chairman
OCR for page R11
Contents
Executive Summary......
ad
1 Background Information and Scientific Principles
Physics and Dosimetry of Ionizing Radiation, 9
Population Exposure to Ionizing Radiation in the
United States, 17
Radiobiological Concepts, 20
Effects of Radiation on Genes and Chromosomes, 31
Internally Deposited Radionuclides: Special Considerations, 38
Use of Animal Studies, 42
Epidemiological Studies: Special Considerations, 44
Risk Assessment Methodology, 49
2 Genetic Effects of Radiation......
Introduction, 65
Summary of Conclusions, 68
Methods of Risk Calculation, 71
Previous Estimates of Human Doubling Dose, 74
Calculation of Risk Estimates, 77
Background Data from Humans, 90
Background Data from Mice and Other Mammals, 97
3 Mechanisms of Radiation-Induced Cancer
Background, 135
Mechanisms, 136
X1
................ 65
....135
OCR for page R12
xii
Genetics of Cancer, 145
Effects of Age, Sex, Smoking, and Other Susceptibility
Factors, 152
4 Risk of C ancer )~! Sites.
Introduction, 161
Model Fitting, 163
Risk Assessment, 171
Uncertainty in Point Estimates of Lifetime Risk, 176
ANNEX 4A Summary of Major Epidemiologic Studies
Used in BEIR V ....................................
ANNEX 4B Changes in the Estimated Dose for
A-Bomb Survivors...............................
ANNEX 4C AMFIT ..............................
ANNEX 4D The Committee's Analysis of A-Bomb
Survivor Data .............
ANNEX 4E
ANNEX 4F
CONTENTS
.......... 161
182
...190
.196
.198
......... 205
Modeling Breast Cancer
Uncertainty, Probability of Causation,
and Diagnostics 217
ANNEX 4G The BEIR IV Committee's Model and
Risk Estimates for Lung Cancer Due to Radon Progeny .239
5 Racliogenic Cancer at Specific Sites
Leukemia, 242
Breast, 253
Lung, 267
Stomach, 278
Thyroid, 281
Esophagus, 298
Small Intestine, 300
Colon and Rectum, 301
Liver, 303
Skeleton, 306
Brain and Nervous System, 310
Ovary, 313
Uterus, 314
Testis, 315
Prostate, 316
Urinary ~act, 318
Parathyroid Glands, 321
Nasal Cavity and Sinuses, 324
Skin, 325
Lymphoma and Multiple Myeloma, 327
242
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CONTENTS
Pharynx, Hypopharynx, and Larynx, 330
Salivary Glands, 331
Pancreas, 333
Other Somatic and Fetal Effects......................
Cancer in Childhood Following Exposure In Utero, 352
Effects on Growth and Development, 354
Cataract of the Eye Lens, 363
Life Shortening, 363
Fertility and Sterility, 364
7 Low Dose Epidemiologic Studies .
Introduction, 371
Diagnostic Radiography: Adult-Onset Myeloid Leukemia, 371
Fallout from Nuclear Weapons Testing, 373
Cancer Among Individuals Near Nuclear Installations, 377
Epidemiologic Studies of Workers Exposed to Low Dose,
Low-LET Radiation, 379
High Natural Background Radiation, 383
Glossary . . .
Index. . .
· . .
x~
..... 352
....371
1
... 391
. .401
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