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News from the National Academies
Date: Feb. 18, 2003
Contacts: Christine Stencel, Media Relations Officer
Chris Dobbins, Media Relations Assistant
Office of News and Public Information
(202) 334-2138; e-mail <news@nas.edu>

For Immediate Release

Report Confirms Earlier Findings on Links Between Health Effects and Insecticides and Solvents Used in Gulf War

WASHINGTON -- A comprehensive assessment of the available scientific literature largely reaffirms what is known already about specific human health effects that have been associated with insecticides and solvents used during the Persian Gulf War. There is some evidence -- usually limited -- to link certain long-term health problems with exposures to a few specific insecticides or solvents, says a new report from the Institute of Medicine (IOM) of the National Academies. However, for the majority of solvents and insecticides that have been studied, there is not enough epidemiologic evidence to determine whether associations exist between diseases and exposures to these chemicals.

"Our exhaustive examination of the literature produced no unexpected findings," said Jack M. Colwill, emeritus professor of family and community medicine, University of Missouri, Columbia, and chair of the committee that wrote the report. "Our conclusions about exposure to insecticides and solvents and long-term health problems largely mirror those reached by many other scientific groups. While we would like to have more definitive answers to questions about the specific diseases that may be associated with these chemicals, in most cases the evidence simply is not strong enough or does not exist."

The committee evaluated the published, peer-reviewed research on exposure to various insecticides and solvents -- such as cleaning agents -- for any evidence of links to specific cancers, neurological effects, or other health problems that occur or persist after exposure. Of the 3,000 studies the committee reviewed, most involved individuals who were exposed to these agents in occupational settings such as agricultural and industrial sites. Only a small number actually studied veterans who may have been exposed while serving in the Persian Gulf. Toxicology studies conducted in animals also were reviewed, but played only a supportive role in this assessment.

The insecticides and solvents used during the Gulf War were agents that have also been used domestically for industrial and personal applications. Insecticides and repellents, primarily DEET and permethrin, were applied by service members to control insects that can carry infectious diseases endemic to the area, such as malaria and leishmaniasis. Personnel came into contact with solvents during activities such as equipment cleaning and vehicle maintenance and repair.

However, little information exists on the use of insecticides or solvents by individual service members, and how that use may have differed from stateside use or exposure. Because scant information exists on actual exposure levels -- a critical factor when assessing health effects -- the committee emphasized that it could not draw specific conclusions about the health problems of Gulf War veterans.

Veterans who have experienced chronic health problems following their service in the Persian Gulf are asking whether exposure to various chemical or biological agents might be responsible. Thousands of troops did come in contact with a number of agents before, during, and after the war. The U.S. Department of Veterans Affairs initially requested an IOM study of potentially harmful chemical, biological, or environmental agents to which Gulf War veterans might have been exposed. Congress subsequently mandated a similar study, listing several specific agents. This report on insecticides and solvents is the second in a series from the IOM that responds to these requests. The first report focused on depleted uranium, pyridostigmine bromide, sarin, and vaccines. The next report will examine the health effects of exposure to selected environmental pollutants and particulates, such as smoke from oil-well fires, diesel heater fumes, and jet fuels.

Weighing the Evidence

The committee carefully assessed the quality, limitations, and applicability of each epidemiologic study it evaluated and used five categories to describe the strength of all the evidence.

Sufficient evidence of a causal relation, the strongest level of evidence, means that many studies have established a clear link between exposure to an agent and a health outcome. Among the other requirements, there must be a plausible biological explanation for the relationship. Evidence that establishes a link between exposures and a health outcome with reasonable certainty, but fails to meet the higher standard of proof needed for causality, is characterized as sufficient evidence of an association. When a limited number of studies suggests that a link exists, but without reasonable certainty, the evidence is said to be limited or suggestive of an association. If several studies of adequate quality consistently fail to show a positive association at any level of exposure, the evidence is described as limited or suggestive of no association. Evidence that lacks sufficient quality, consistency, or statistical power to draw any conclusion is judged to be inadequate or insufficient to determine whether an association exists. The majority of the evidence for insecticides and solvents fell into this final category.
Benzene and Cancer

The only clear causal relationships that the committee found between health effects and these chemicals were the well-established links between the solvent benzene and acute leukemia and aplastic anemia. Benzene has long been recognized as a cancer-causing agent by all major national and international public health organizations. The committee had no data on the extent of Gulf War personnel's exposure to benzene, but it was likely to have been of shorter duration than the years of exposure typical of occupational workers who were the focus of the available studies. Benzene was also confirmed to be associated with adult leukemia, although a direct causal link could not be determined.

Other Health Links

Most of the other health effects associated with exposure to insecticides or solvents were not as clear-cut. The committee found limited or suggestive evidence that a few of these chemicals, including benzene and organophosphorous (OP) and carbamate insecticides, may be associated with non-Hodgkin's lymphoma. Neither DEET nor permethrin, the pest-control agents most commonly used during the Gulf War, are members of these insecticide classes. In addition, limited evidence suggests that tetrachloroethylene and other dry-cleaning solvents are linked to bladder and kidney cancer. Solvents in general appear to have some connection to adult leukemia.

Neurobehavioral problems, such as fatigue, pain, loss of concentration, forgetfulness, and headaches, are some of the most common complaints of Gulf War veterans. These health effects appear to have a limited association with solvents in general and with OP insecticides in cases where exposure is high enough to be immediately life threatening. For lower levels of OP insecticide exposure, the committee could not reach full agreement on whether there is a link to neurobehavioral effects in human studies. OP insecticides are similar to the chemical nerve agent sarin, which was reviewed by the committee in its first report issued in 2000. That report also found limited or suggestive evidence of neurobehavioral effects after exposure to sarin at levels that would produce immediate signs and symptoms.

There was insufficient or inadequate evidence to determine whether DEET and permethrin have long-term health effects in humans. The committee did not look at whether a combination of DEET or permethrin and pyridostigmine bromide, a drug given prophylactically to protect against nerve gas, could cause adverse health effects because there are no relevant studies in humans. Moreover, most human studies analyze the possible effects of individual substances only. More research is needed on the possible outcomes of exposures to combinations of different agents, the report says.

There was insufficient or inadequate evidence to associate any insecticides or solvents with neurological diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease, or Alzheimer's disease. There also is not enough evidence to determine whether any association exists between insecticides or solvents and breast and uterine cancers. However, the committee could not reach agreement on the possible relationships between cervical cancer and trichloroethylene, between benzene and cancers of the brain or central nervous system, and between exposure to solvents and the development of leukemia in children later born to the exposed individuals. In each case, the committee members differed on whether the available epidemiologic evidence was sufficient to suggest a possible association or was inadequate to point to a link.

The study was sponsored by the U.S. Department of Veterans Affairs. The Institute of Medicine is a private, nonprofit institution that provides health policy advice under a congressional charter granted to the National Academy of Sciences. A committee roster follows.

Read the full text of Gulf War and Health Volume II: Insecticides and Solvents for free on the Web, as well as more than 2,500 other publications from the National Academies. Printed copies are available for purchase from the National Academies Press Web site or by calling (202) 334-3313 or 1-800-624-6242. Reporters may obtain a pre-publication copy from the Office of News and Public Information (contacts listed above)."

INSTITUTE OF MEDICINE
Board on Health Promotion and Disease Prevention

Committee on Gulf War and Health: Literature Review of Pesticides and Solvents

Jack M. Colwill, M.D. (chair)
Professor Emeritus
School of Medicine
University of Missouri
Columbia

Samuel J. Potolicchio, M.D. (vice chair)
Professor
Department of Neurology
George Washington University Medical Center
Washington, D.C.

Ann Aschengrau, Sc.D.
Professor
Department of Epidemiology
Boston University School of Public Health
Boston

Lorne A. Becker, M.D.
Chair
Department of Family Medicine
Upstate Medical University
State University of New York
Syracuse

Deborah A. Cory-Slechta, Ph.D.
Professor and Chair
Department of Environmental Medicine
University of Rochester
Rochester, N.Y.

William E. Daniell, M.D., M.P.H.
Associate Professor
Department of Environmental Health
School of Public Health and
Community Medicine
University of Washington
Seattle

Marion F. Ehrich, Ph.D.
Professor
Virginia-Maryland Regional College of Veterinary Medicine
Virginia Polytechnic Institute and State University
Blacksburg

Manning Feinleib, M.D., Dr.P.H.
Professor of Epidemiology
Johns Hopkins Bloomberg School of Public Health
Baltimore

Robert G. Feldman, M.D.
Professor of Neurology
Boston University School of Medicine
Boston

Mark S. Goldberg, Ph.D.
Associate Professor
Department of Epidemiology and Biostatistics
McGill University
Montreal, Quebec
Canada

Lynn R. Goldman, M.D., M.P.H.
Professor
Johns Hopkins Bloomberg School of Public Health
Baltimore

Rose H. Goldman, M.D., M.P.H.
Associate Professor of Medicine
Harvard Medical School, and
Associate Professor
Department of Environmental Health
Harvard School of Public Health
Boston

Ronald Goldner, M.D.
Clinical Professor of Dermatology
University of Maryland School of Medicine
Baltimore

David F. Goldsmith, M.S.P.H., Ph.D.
Associate Research Professor
George Washington University
Washington, D.C.

Cynthia Harris, Ph.D., D.A.B.T.
Director and Associate Professor
College of Pharmacy and Pharmaceutical Sciences
Florida A&M University
Tallahassee

Russ B. Hauser, M.D., Sc.D., M.P.H.
Assistant Professor
Occupational Health Program
Harvard School of Public Health
Boston

Janice L. Kirsch, M.D., M.P.H.
Study Oncologist and Researcher
Northern California Childhood Leukemia Project
University of California
Berkeley

Anthony L. Komaroff, M.D.
Professor of Medicine
Harvard Medical School
Boston

Michael L. Lefevre, M.D., M.S.P.H.
Director of Clinical Services
Department of Family and
Community Medicine
School of Medicine
University of Missouri
Columbia

Richard Mayeux, M.D.
Gertrude H. Sergievsky Professor
of Neurology, Psychiatry, and Public Health
Columbia University
New York City

Stephen A. McCurdy, M.D., M.P.H.
Associate Professor of Medicine
University of California
Davis

Sandra Mohr, M.D., M.P.H.
Former Residency Director
Division of Environmental and Occupational Health
National Jewish Medical and Research Center
Denver

Toshio Narahashi, Ph.D., D.V.M.
John Evans Professor of Pharmacology, and
Alfred Newton Richards Professor of Pharmacology
Northwestern University
Chicago

Leena A. Nylander-French, Ph.D.
Assistant Professor
Department of Environmental Sciences
and Engineering
University of North Carolina
Chapel Hill

Michael O'Malley, M.P.H.
Staff Physician
Employee Health Service
University of California
Davis

Charles Poole, M.P.H., Sc.D.
Associate Professor
Department of Epidemiology
University of North Carolina
Chapel Hill

Carrie A. Redlich, M.D., M.P.H.
Associate Professor
Department of Medicine
Occupational and Environmental
Medicine Program
Yale University School of Medicine
New Haven, Conn.

Joseph V. Rodricks, Ph.D.
Principal
Environ Inc.
Arlington, Va.

Kenneth D. Rosenman, M.D.
Professor
Department of Medicine
Michigan State University
East Lansing

Mary Ann Smith, Ph.D.
Assistant Professor
School of Public Health
University of Texas
Houston

Anne M. Sweeney, Ph.D.
Associate Professor
School of Rural Public Health
Texas A&M University
Bryan

Patrick R.M. Thomas, M.D.
Radiation Oncologist
Bardmoor Cancer Center
Largo, Fla.

William M. Valentine, Ph.D., D.V.M.
Associate Professor
Department of Pathology
Vanderbilt University Medical Center
Nashville, Tenn.

John E. Vena, Ph.D.
Professor
Department of Social and Preventive Medicine, and
Director
Environmental and Society Institute
University of Buffalo
Buffalo, N.Y.

Laura Stewart Welch, M.D.
Director
Occupational and Environmental Medicine
Washington Hospital Center
Washington, D.C.

Christina Wolfson, Ph.D.
Associate Professor
Department of Epidemiology and Biostatistics
McGill University
Montreal, Quebec
Canada

Tongzhang Zheng, M.D.
Associate Professor
Division of Environmental Health Sciences
Yale University School of Public Health
New Haven, Conn.

INSTITUTE STAFF

Carolyn Fulco
Study Director