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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Subcommittee to Review Permethrin Toxicity from Military Uniforms
Committee on Toxicology
Board on Environmental Studies and Toxicology
Commission on Life Sciences
National Research Council
NATIONAL ACADEMY PRESS
Washington, D.C.
1994
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
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 competencies 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.
The project was supported by the U.S. Army under contract No.DAMD 17-89-C-9086.
Additional copies of this report are available from the Board on Environmental Studies and Toxicology, 2101 Constitution Avenue, N.W., Washington, D.C. 20418
Copyright 1994 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Subcommittee to Review Permethrin Toxicity from Military Uniforms
ERNEST EUGENE MCCONNELL (Chair), Consultant,
Raleigh, N.C.
IAN GREAVES,
University of Minnesota, Minneapolis, Minn.
CAROLE KIMMEL,
U.S. Environmental Protection Agency, Washington, D.C.
RALPH KODELL,
U.S. Food and Drug Administration, Jefferson, Ark.
LOREN KOLLER,
Oregon State University, Corvallis, Oreg.
MICHELE MEDINSKY,
Chemical Industry Institute of Toxicology, Research Triangle Park, N.C.
ANNE WOLVEN-GARRET, Consultant,
Atlanta, Ga.
Staff
KULBIR S. BAKSHI, Project Director and Program Director
RICHARD D. THOMAS, Program Director (until May 1994)
RUTH E. CROSSGROVE, Editor
CATHERINE M. KUBIK, Senior Program Assistant
WANDA J. SMARR, Project Assistant
Sponsor: U.S. Army
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Committee on Toxicology
ROGENE F. HENDERSON (Chair),
Lovelace Biomedical and Environmental Research Institute, Albuquerque, N.Mex.
R. HAYS BELL,
Eastman Kodak Company, Rochester, N.Y.
DEAN E. CARTER,
University of Arizona, Tucson, Ariz.
DEBORAH A. CORY-SLECHTA,
University of Rochester School of Medicine, Rochester, N.Y.
CHARLES E. FEIGLEY,
University of South Carolina, Columbia, S.C.
DONALD E. GARDNER,
ManTech Environmental Technology, Inc., Research Triangle Park, N.C.
DAVID W. GAYLOR,
U.S. Food and Drug Administration, Jefferson, Ark.
WALDERICO M. GENEROSO,
Oak Ridge National Laboratory, Oak Ridge, Tenn.
IAN A. GREAVES,
University of Minnesota, Minneapolis, Minn.
SIDNEY GREEN,
U.S. Food and Drug Administration, Laurel, Md.
CAROLE A. KIMMEL,
U.S. Environmental Protection Agency, Washington, D.C.
LOREN D. KOLLER,
Oregon State University, Corvallis, Oreg.
ERNEST EUGENE MCCONNELL,
Raleigh, N.C.
MICHELE A. MEDINSKY,
Chemical Industry Institute of Toxicology, Research Triangle Park, N.C.
ROBERT SNYDER,
Rutgers University, Piscataway, N.J.
BAILUS WALKER, JR.,
University of Oklahoma, Oklahoma City, Okla.
HANSPETER R. WITSCHI,
University of California, Davis, Calif.
GERALD N. WOGAN,
Massachusetts Institute of Technology, Cambridge, Mass.
GAROLD S. YOST,
University of Utah, Salt Lake City, Utah
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Staff of Committee on Toxicology
KULBIR S. BAKSHI, Program Director
RICHARD D. THOMAS, Program Director (until May 1994)
MARVIN A. SCHNEIDERMAN, Senior Staff Scientist
RUTH E. CROSSGROVE, Editor
CATHERINE M. KUBIK, Senior Program Assistant
RUTH P. DANOFF, Project Assistant (until November 1993)
WANDA SMARR, Project Assistant
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Board on Environmental Studies and Toxicology
PAUL G. RISSER (Chair),
Miami University, Oxford, Ohio
FREDERICK R. ANDERSON,
Cadwalader, Wickersham & Taft, Washington, D.C.
MICHAEL J. BEAN,
Environmental Defense Fund, Washington, D.C.
EULA BINGHAM,
University of Cincinnati, Cincinnati, Ohio
EDWIN H. CLARK,
Clean Sites, Inc., Alexandria, Va.
ALLAN H. CONNEY,
Rutgers University, Piscataway, N.J.
JOHN L. EMMERSON,
Eli Lilly & Company, Greenfield, Ind.
ROBERT C. FORNEY,
Unionville, Pa.
ROBERT A. FROSCH,
Harvard University, Cambridge, Mass.
KAI LEE,
Williams College, Williamstown, Mass.
JANE LUBCHENCO,
Oregon State University, Corvallis, Oreg.
GORDON ORIANS,
University of Washington, Seattle, Wash.
FRANK L. PARKER,
Vanderbilt University, Nashville, Tenn., and Clemson University, Anderson, S.C.
GEOFFREY PLACE,
Hilton Head, S.C.
DAVID P. RALL,
Washington, D.C.
LESLIE A. REAL,
Indiana University, Bloomington, Ind.
KRISTIN SHRADER-FRECHETTE,
University of South Florida, Tampa, Fla.
GERALD VAN BELLE,
University of Washington, Seattle, Wash.
BAILUS WALKER, JR.,
Washington, D.C.
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Staff of Board on Environmental Studies and Toxicology
JAMES J. REISA, Director
DAVID J. POLICANSKY, Associate Director and Program Director for
Natural Resources and Applied Ecology
GAIL CHARNLEY, Acting Program Director for
Human Toxicology and Risk Assessment (since May 1994)
RICHARD D. THOMAS, Associate Director and Program Director for
Human Toxicology and Risk Assessment (until May 1994)
LEE R. PAULSON, Program Director for
Information Systems and Statistics
RAYMOND A. WASSEL, Program Director for
Environmental Sciences and Engineering
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Commission on Life Sciences
THOMAS D. POLLARD (Chair),
Johns Hopkins Medical School, Baltimore, Md.
BRUCE N. AMES,
University of California, Berkeley, Calif.
JOHN C. BAILAR, III,
McGill University, Montreal, Quebec
MICHAEL BISHOP,
Hooper Research Foundation, University of California Medical Center, San Francisco, Calif.
JOHN E. BURRIS,
Marine Biological Laboratory, Woods Hole, Mass.
MICHAEL T. CLEGG,
University of California, Riverside, Calif.
GLENN A. CROSBY,
Washington State University, Pullman, Wash.
LEROY E. HOOD,
University of Washington, Seattle, Wash.
MARIAN E. KOSHLAND,
University of California, Berkeley, Calif.
RICHARD E. LENSKI,
Michigan State University, East Lansing, Mich.
EMIL A. PFITZER,
Hoffmann-La Roche Inc., Nutley, N.J.
MALCOLM C. PIKE,
University of Southern California School of Medicine, Los Angeles, Calif.
HENRY C. PITOT, III,
University of Wisconsin, Madison, Wisc.
PAUL G. RISSER,
Miami University, Oxford, Ohio
JOHNATHAN M. SAMET,
University of New Mexico School of Medicine, Albuquerque, N.Mex.
HAROLD M. SCHMECK, JR.,
Armonk, N.Y.
CARLA J. SHATZ,
University of California, Berkeley, Calif.
SUSAN S. TAYLOR,
University of California at San Diego, La Jolla, Calif.
P. ROY VAGELOS,
Merck & Company, Whitehouse Station, N. J.
JOHN L. VANDEBERG,
Southwestern Foundation for Biomedical Research, San Antonio, Tex.
TORSTEN N. WIESEL,
Rockefeller University, New York, N.Y.
PAUL GILMAN, Executive Director
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Other Recent Reports of The Board on Environmental Studies and Toxicology
Science and Judgment in Risk Assessment (1994)
Environmental Information for Outer Continental Shelf Oil and Gas Decisions (1994)
Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations (1993)
Health Effects of Ingested Fluoride (1993)
Pesticides in the Diets of Infants and Children (1993)
Issues in Risk Assessment (1993)
Setting Priorities for Land Conservation (1993)
Protecting Visibility in National Parks and Wilderness Areas (1993)
Biologic Markers in Immunotoxicology (1992)
Dolphins and the Tuna Industry (1992)
Environmental Neurotoxicology (1992)
Hazardous Materials on the Public Lands (1992)
Science and the National Parks (1992)
Animals as Sentinels of Environmental Health Hazards (1991)
Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I-IV (1991-1993)
Human Exposure Assessment for Airborne Pollutants (1991)
Monitoring Human Tissues for Toxic Substances (1991)
Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)
Decline of the Sea Turtles (1990)
Tracking Toxic Substances at Industrial Facilities (1990)
Biologic Markers in Pulmonary Toxicology (1989)
Biologic Markers in Reproductive Toxicology (1989)
These reports may be ordered from the National Academy Press(800) 624-6242 or (202) 334-3313
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Preface
Military personnel sometimes must be rapidly deployed to areas where life-threatening, insect-borne diseases are prevalent. This places such personnel at an increased risk of contracting diseases such as malaria, scrub typhus, leishmaniasis, and Lyme disease. The suddenness of deployments and movement after deployment often precludes the use of protection or control measures. To protect against specific disease risks from insect bites, the U.S. Army has formulated a clothing impregnant containing permethrin, a pyrethroid insecticide that is effective against disease vectors such as mosquitoes, ticks, and other arthropods. The Army proposes to use permethrin-impregnated fabric to manufacture battle-dress uniforms (BDUs). BDUs, made from either 100% cotton fabric or 50% nylon and 50% cotton fabric, are used to camouflage soldiers.
The U.S. Environmental Protection Agency has classified permethrin as a potential carcinogen, so there might be concern that soldiers wearing permethrin-impregnated BDUs would face an unacceptable level of cancer risk. In response to that potential concern, the Army requested that the National Research Council (NRC) review the toxicological and exposure data and make recommendations regarding long-term exposure to permethrin. This project was assigned to the NRC's Committee on Toxicology (COT). The Subcommittee on Permethrin Toxicity from Military Uniforms was established within COT to perform this task. The subcommittee reviewed the toxicity data as well as the exposure and pharmacokinetic data on permethrin and assessed the suitability of military personnel wearing permethrin-impregnated BDUs on a long-term basis. The report of the subcommittee is intended for use by the Army
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
in deciding whether to impregnate BDUs with permethrin to protect soldiers from arthropod-borne diseases. The subcommittee in this report also assessed the risk to garment workers who handle permethrin-impregnated fabric.
The subcommittee gratefully acknowledges Lieutenant Colonel Holly Doyne, Colonel Frederick Erdtmann, and Colonel Eric Evenson of the U.S. Army for their interest and support of the project. We also thank other persons who provided information for the subcommittee, including Major Stephen Berté, Lieutenant Colonel Phillip Pierce, Lieutenant Colonel Lyman Roberts, Hubert Snodgrass (all of the U.S. Army), and David Taplin (University of Miami).
We are grateful to the NRC's anonymous reviewers for their many helpful comments and suggestions that have resulted in improvements of the subcommittee's report. This report could not have been produced without the untiring efforts of the NRC staff, including James J. Reisa, director, Board on Environmental Studies and Toxicology; Richard D. Thomas, program director, COT; Ruth E. Crossgrove, editor; Wanda Smarr, project assistant; and Catherine Kubik, senior program assistant.
The subcommittee especially acknowledges its great debt to Kulbir S. Bakshi, who not only ably fulfilled the role of project director, but contributed substantially to the drafting and revision of the report. Without his skills and input, our task could never have been completed in the timely manner it has been.
Finally, we would like to thank all members of the subcommittee for their expertise, input, and support throughout our deliberations.
Ernest Eugene McConnell, Chair
Subcommittee to Review Permethrin
Toxicity from Military Uniforms
Rogene F. Henderson, Chair
Committee on Toxicology
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
Contents
SUMMARY
1
1
INTRODUCTION
17
2
EXPOSURE ASSESSMENT
23
Military Nonfield Personnel
23
Military Field Personnel
25
Garment Workers
25
Recommendations
26
3
PHARMACOKINETICS OF PERMETHRIN
27
Absorption of Permethrin
27
Interactions
31
Metabolism
32
Hydrolysis
34
Oxidation
35
Relationship to Toxicity
35
Elimination
37
Distribution
38
Summary and Conclusions
39
Recommendations
40
4
ACUTE AND SHORT-TERM TOXICITY OF PERMETHRIN
43
Acute Toxicity
43
Subacute and Subchronic Toxicity
48
Conclusions
55
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Health Effects of Permethrin-Impregnated Army Battle-Dress Uniforms
5
DERMAL AND OCULAR TOXICITY OF PERMETHRIN
57
Dermal Toxicity
57
Ocular Toxicity
64
Conclusions
65
6
NEUROTOXICITY OF PERMETHRIN
67
Human Data
68
Animal Data
68
Conclusions
71
Recommendations
72
7
LIVER AND OTHER ORGAN TOXICITY OF PERMETHRIN
73
Liver Toxicity
73
Other Organ Toxicity
74
Conclusions
75
8
IMMUNOTOXICITY OF PERMETHRIN
77
Conclusions
78
Recommendations
78
9
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF PERMETHRIN
79
Rat Studies
80
Mouse Studies
82
Rabbit Studies
82
Other Studies
82
Conclusions
84
10
GENOTOXICITY OF PERMETHRIN
87
Gene Mutations
87
Chromosomal Effects
88
Other Genotoxic Effects
91
Conclusions
91
11
CARCINOGENICITY OF PERMETHRIN
93
Carcinogenicity Studies in Mice
93
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Carcinogenicity Studies in Rats
98
Tumor Promotion Studies: Shimkin Mouse Lung Bioassay
101
Conclusions
101
Carcinogenicity Risk Assessment
102
12
SUMMARY OF RECOMMENDATIONS
107
Exposure Assessment
108
Pharmacokinetics
108
Dermal Toxicity
109
Neurotoxicity
110
Immunotoxicity
110
Genotoxicity
110
REFERENCES
113
APPENDIX A
129