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Gulf War and Health: Updated Literature Review of Depleted Uranium
GULF WAR and HEALTH
UPDATED LITERATURE REVIEW OF DEPLETED URANIUM
Committee on Gulf War and Health: Updated Literature Review of Depleted Uranium
Board of Population Health and Public Health Practice
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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Gulf War and Health: Updated Literature Review of Depleted Uranium
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, NW 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 Contract V101(049A3)-P-0066 between the National Academy of Sciences and the Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-11919-1
International Standard Book Number-10: 0-309-11919-7
Additional copies of this report are available from the
National Academies Press,
500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at www.iom.edu.
Copyright 2008 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2008. Gulf war and health: Updated literature review of depleted uranium. Washington, DC: The National Academies Press.
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Gulf War and Health: Updated Literature Review of Depleted Uranium
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
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Gulf War and Health: Updated Literature Review of Depleted Uranium
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and 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. 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 engineers. Dr. Charles M. Vest 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. 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 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. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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Gulf War and Health: Updated Literature Review of Depleted Uranium
COMMITTEE ON GULF WAR AND HEALTH: UPDATED LITERATURE REVIEW OF DEPLETED URANIUM
DAVID G. HOEL, PhD (Chair), Distinguished University Professor,
Medical University of South Carolina, Charleston, SC
MICHAEL ASCHNER, PhD, Gray E.B. Stahlman Professor of Neuroscience,
Vanderbilt University, Nashville, TN
MELISSA D. BEGG, ScD, Professor of Clinical Biostatistics and Director of Academic Programs,
Mailman School of Public Health of Columbia University, New York
H. TIM BORGES, PhD, Research Staff Member,
Oak Ridge National Laboratory, Oak Ridge, TN (resigned February 2008)
VIVIEN W. CHEN, MPH, PhD, Professor and Director of Epidemiology Program,
School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA
HAROLD I. FELDMAN, MD, MSCE, Professor of Medicine and Epidemiology,
University of Pennsylvania School of Medicine, Philadelphia, PA
PHILIP HARBER, MD, MPH, Professor and Chief,
Division of Occupational and Environmental Medicine, David Geffen School of Medicine, University of California, Los Angeles
PATRICK J. HEAGERTY, PhD, Professor of Biostatistics,
University of Washington School of Public Health and Community Medicine, Seattle, WA
KIYOUNG LEE, MPH, ScD, Assistant Professor,
University of Kentucky College of Public Health and Seoul National University School of Public Health, Republic of Korea
JONATHAN LINKS, PhD, Professor and Director,
Center for Public Health Preparedness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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Gulf War and Health: Updated Literature Review of Depleted Uranium
STAFF
ABIGAIL E. MITCHELL, PhD, Senior Program Officer
PETER JAMES, Senior Program Associate (through May 2007)
A. WEZI MUNTHALI, MPH, Senior Program Associate (through November 2007)
DEEPALI M. PATEL, Senior Program Associate (through November 2007)
JENNIFER E. SAUNDERS, MPP, MPH, Senior Program Associate (from November 2007)
RENEE WLODARCZYK, Research Assistant
JOSEPH GOODMAN, Senior Program Assistant
DANIELLE K. STOLL, Intern
NORMAN GROSSBLATT, Senior Editor
ROSE MARIE MARTINEZ, ScD, Director,
Board on Population Health and Public Health Practice
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Gulf War and Health: Updated Literature Review of Depleted Uranium
Reviewers
This report has been reviewed in draft form by persons 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 institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their review of this report:
Odile David, University of Illinois College of Medicine
Fletcher Hahn, Lovelace Respiratory Research Institute, Scientist Emeritus
Robert Herrick, Department of Environmental Health, Harvard School of Public Health
Howard Hu, University of Michigan Schools of Public Health and Medicine
Ronald L. Kathren, Washington State University, Professor Emeritus
William N. Rom, Division of Pulmonary and Critical Care Medicine, New York University School of Medicine
Michael J. Thun, Epidemiology and Surveillance Research, American Cancer Society
Bailus Walker, Jr., Howard University Medical Center
Walter Willett, Department of Nutrition, Harvard School of Public Health
Judith T. Zelikoff, Department of Environmental Medicine, New York University School of Medicine
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Gulf War and Health: Updated Literature Review of Depleted Uranium
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by David J. Tollerud, School of Public Health and Information Sciences, University of Louisville, and Johanna T. Dwyer, Tufts University School of Medicine and Friedman School of Nutrition Science, Tufts-New England Medical Center. Appointed by the Institute of Medicine and the National Research Council, respectively, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
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Contents
SUMMARY
1
1
INTRODUCTION
7
Summary of Findings in the Section on Depleted Uranium in Gulf War and Health, Volume 1,
9
The Department of Veterans Affairs Request for This Study,
9
The Committee’s Task,
10
Organization of This Report,
10
References,
10
2
BACKGROUND
13
Uses of Depleted Uranium,
14
Exposure of Military Personnel to Depleted Uranium,
14
Radiologic and Chemical Effects of Exposure to Depleted Uranium,
17
Dose-Response Modeling and Risk Assessment,
20
References,
21
3
TOXICOLOGY
23
Summary of Previous Report,
24
Toxicokinetics,
25
Toxicity Studies,
29
Application of the Toxicologic Data,
41
References,
66
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4
METHODOLOGY
73
Information-Gathering Strategy,
73
Principal Objectives of Epidemiologic Studies,
75
Factors Influencing the Relevance and Quality of Studies,
76
Epidemiologic-Study Designs,
84
Inclusion Criteria,
88
Rationale for Not Including Studies of Uranium Miners,
88
Categories of Strength of Association,
90
References,
91
5
EXPOSURE ASSESSMENT
93
Estimation of Exposure to Depleted Uranium During the Gulf War,
93
Exposure-Monitoring Methods,
100
References,
102
6
CLINICAL END POINTS OF INTEREST
105
Cancer Outcomes,
105
Noncancer Outcomes,
111
References,
115
7
COHORT DESCRIPTIONS
117
Uranium-Processing Cohorts,
118
Depleted-Uranium Studies,
143
Environmental-Exposure Studies,
153
Summary,
163
References,
190
8
CONCLUSIONS
193
Cancer Outcomes,
193
Noncancer Outcomes,
203
Summary,
214
References,
259
INDEX
263
TABLES AND BOXES
(Note that the tables for Chapters 3, 7, and 8 are at the ends of the chapters)
Tables
3-1
Uranium Compounds, by Dissolution Type,
42
3-2
Carcinogenic Effects,
43
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3-3
Genotoxic Effects,
45
3-4
Respiratory Effects,
51
3-5
Renal Effects,
52
3-6
Neurologic Effects,
53
3-7
Hepatic Effects,
58
3-8
Reproductive and Developmental Effects,
59
3-9
Immunologic Effects,
62
3-10
Musculoskeletal Effects,
64
5-1
Comparison of Level I Exposure Estimates and Risk,
97
5-2
Comparison of Level II Exposure Estimates and Risk,
99
5-3
Comparison of Level III Exposure Estimates and Risk,
99
7-1
Studies of Uranium Processors,
164
7-2
Studies of Depleted-Uranium–Exposed Persons,
178
7-3
Studies of Environmental Exposure to Uranium,
184
8-1
Lung Cancer,
216
8-2
Lung Cancer in the Oak Ridge, Tennessee, Cohort,
220
8-3
Leukemia,
221
8-4
Hodgkin Lymphoma,
224
8-5
Non-Hodgkin Lymphoma and Other Lymphatic Cancers,
226
8-6
Bone Cancer,
230
8-7
Renal Cancer,
232
8-8
Bladder Cancer,
234
8-9
Cancers of the Central Nervous System,
236
8-10
Stomach Cancer,
238
8-11
Prostatic Cancer,
240
8-12
Testicular Cancer,
242
8-13
Mortality from Nonmalignant Renal Disease,
244
8-14
Nonmalignant Renal Disease—Morbidity Risk,
246
8-15
Mortality from Nonmalignant Respiratory Disease,
252
8-16
Nonmalignant Respiratory Disease—Morbidity Risk,
254
8-17
Mortality from Neurologic Disease,
255
8-18
Reproductive and Developmental Effects,
256
Boxes
1-1
Agents Specified in PL 105-277 and PL 105-368,
8
2-1
Units of Measurement,
18
4-1
Open-Session Presentations, June 28, 2007,
74
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