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News from the National Academies
Date: March 14, 1996
Contacts: Dan Quinn, Media Relations Associate
Darice Griggs, Media Relations Assistant
(202) 334-2138; Internet <news@nas.edu>

EMBARGOED: NOT FOR PUBLIC RELEASE BEFORE NOON EST THURSDAY, MARCH 14

AGENT ORANGE UPDATE SUPPORTS ASSOCIATION
BETWEEN HERBICIDES AND VETERANS' DISEASES

WASHINGTON -- New evidence supports the association between chemicals used in herbicides in the Vietnam War and various cancers and other health problems, a committee of the Institute of Medicine (IOM) said in the first update of IOM's 1994 landmark report on veterans and Agent Orange. The congressionally mandated report* confirms the earlier finding that there is sufficient evidence of a link to soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, and chloracne. And it says there is new "limited or suggestive" evidence to show an association with the congenital birth defect spina bifida in veterans' children, and with a neurological disorder in veterans.

"We still do not know the precise degree of risk from Agent Orange exposure for individual Vietnam veterans, but the base of research has improved," said committee chair David Tollerud, associate professor and chief of the division of occupational and environmental medicine at the University of Pittsburgh Graduate School of Public Health. "The newest studies give us hope that researchers are getting closer to answering the lingering questions about the health effects of herbicide exposure."

Using the latest scientific studies, the committee re-evaluated the health effects of exposure to the chemical defoliant Agent Orange and other herbicides used in Vietnam, some of which contained dioxin. The committee classified diseases into four categories, following the form of the first report: sufficient evidence of a statistical association between the disease and exposure to herbicides or dioxin; limited or suggestive evidence; inadequate or insufficient evidence to determine whether an association exists; or limited, suggestive evidence of no association.

The results of three epidemiological studies suggest that a father's exposure to herbicides may put his children at a greater risk of being born with spina bifida, which is characterized by a deformity of the spine and spinal cord and can cause neurological problems. The largest of these studies -- the Ranch Hand study -- looks at a group of veterans who were directly involved in spraying the bulk of the nearly 19 million gallons of chemical defoliant in Vietnam during the war. In the two years since the first IOM report, the Ranch Hand results have been reanalyzed by the U.S. Air Force, and this new analysis bolstered the evidence from other studies, leading to the committee's conclusion that there is limited or suggestive evidence of an association.

A classification of limited or suggestive evidence means that while at least one major, high-quality epidemiological study has found a link between disease and exposure, the evidence is not yet conclusive enough to say definitively that chance or study bias did not influence the study results, or that the studies have isolated all of the variables that could have affected the outcome. Other diseases in the limited or suggestive category include prostate cancer, multiple myeloma, and respiratory cancers of the lung, larynx, or trachea (see attached table below).

The committee also found limited or suggestive evidence that herbicide or dioxin exposure may be associated with the acute, transient form of peripheral neuropathy, a nerve disorder which can lead to pain, numbness, and weakness in the limbs; and with porphyria cutanea tarda, or PCT, a rare skin disease that can involve thinning and blistering of the skin in areas exposed to the sun. Several occupational studies link herbicide exposure to the transient peripheral neuropathy, from which patients recover over a period of weeks, months, or longer. The association with PCT was downgraded from "sufficient" to "suggestive" evidence, based on studies completed since the first IOM report was issued.

The ability of researchers to pinpoint the health risks faced by veterans is hampered by inadequate information about exposure levels of troops in Vietnam. Some of the evidence reviewed by the committee comes from evaluations of Air Force and Army troops who worked with herbicides. Most documentation, however, is from studies of people who were exposed to herbicides on the job or in industrial accidents. Although most veterans probably experienced lower levels of exposure than those who work with the chemicals over long periods in occupational or agricultural settings, it is difficult to say precisely which veterans may have encountered higher levels.

U.S. forces sprayed Agent Orange and other defoliants over 3.6 million acres in Vietnam beginning in 1962. Most large-scale sprayings were conducted using airplanes and helicopters, but considerable quantities of herbicides were sprayed from boats and ground vehicles or by soldiers wearing back-mounted equipment. A scientific report in 1969 concluded that one of the primary chemicals used in Agent Orange could cause birth defects in laboratory animals. The U.S. military suspended use of Agent Orange in 1970 and halted all herbicide spraying in Vietnam the following year.

The IOM committee found that, in general, it is not possible to quantify the degree of risk to Vietnam veterans from exposure to herbicides. Two members of the committee said, however, that there are certain circumstances under which the risk to veterans can be quantified. Their separate statement is included in an appendix to the report.

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

* Pre-publication copies of Veterans and Agent Orange: Update 1996 are available from the National Academy Press at the mailing address in the letterhead; tel. (202) 334-3313 or 1-800-624-6242. The cost of the report is $49.00 (prepaid) plus shipping charges of $4.00 for the first copy and $.50 for each additional copy. Reporters may obtain copies from the Office of News and Public Information at the letterhead address (contacts listed above).


INSTITUTE OF MEDICINE
Division of Health Promotion and Disease Prevention

Committee to Review the Health Effects in
Vietnam Veterans of Exposure to Herbicides


David Tollerud (chair)
Associate Professor and Chief
Division of Occupational and Environmental Medicine
University of Pittsburgh

Michael Aminoff
Professor, Department of Neurology
University of California School of Medicine
San Francisco

Jesse Berlin
Research Associate Professor
Center for Clinical Epidemiology and Biostatistics
University of Pennsylvania School of Medicine
Philadelphia

Karen Bolla
Associate Professor, Department of Neurology
Johns Hopkins University School of Medicine
Baltimore

Graham Colditz
Associate Professor of Medicine
Harvard Medical School
Boston

Christopher Goetz
Professor, Department of Neurologic Sciences
Rush-Presbyterian-St. Luke's Medical Center
Chicago

Seymour Grufferman
Professor and Chairman
Department of Family Medicine and Clinical Epidemiology
University of Pittsburgh School of Medicine

S. Katharine Hammond
Associate Professor, Department of Environmental Health Sciences
School of Public Health
University of California
Berkeley

David Kriebel
Associate Professor, Department of Work Environment
University of Massachusetts
Lowell

Bryan Langholz
Associate Professor of Research, Department of Preventive Medicine
University of Southern California School of Medicine
Los Angeles

William Nicholson
Professor
Mount Sinai School of Medicine
New York City

Peter Nowell*
Professor, Department of Pathology and Laboratory Medicine
University of Pennsylvania School of Medicine
Philadelphia

Andrew Olshan
Assistant Professor, Department of Epidemiology
School of Public Health
University of North Carolina
Chapel Hill

Malcolm Pike*
Chairman
Preventive Medicine
University of Southern California School of Medicine
Los Angeles

Ken Ramos
Professor, Department of Physiology and Pharmacology
College of Veterinary Medicine
Texas A&M University
College Station

Noel Rose
Professor, Department of Molecular Microbiology and Immunology
Johns Hopkins University School of Hygiene and Public Health
Baltimore


INSTITUTE OF MEDICINE STAFF

Michael A. Stoto
Division Director

David A. Butler
Study Director

* Member, Institute of Medicine


Reprinted from Veterans and Agent Orange: Update 1996

TABLE 1-1 Updated Summary of Findings in Occupational, Environmental, and Veterans Studies Regarding the Association Between Specific Health Problems and Exposure to Herbicides*

Sufficient Evidence of an Association
Evidence is sufficient to conclude that there is a positive association. That is, a positive association has been observed between herbicides and the outcome in studies in which chance, bias, and confounding could be ruled out with reasonable confidence. For example, if several small studies that are free from bias and confounding show an association that is consistent in magnitude and direction, there may be sufficient evidence for an association. There is sufficient evidence of an association between exposure to herbicides and the following health outcomes:

Soft-tissue sarcoma
Non-Hodgkin's lymphoma
Hodgkin's disease
Chloracne

Limited/Suggestive Evidence of an Association
Evidence is suggestive of an association between herbicides and the outcome but is limited because chance, bias, and confounding could not be ruled out with confidence. For example, at least one high-quality study shows a positive association, but the results of other studies are inconsistent. There is limited/suggestive evidence of an association between exposure to herbicides and the following health outcomes:

Respiratory cancers (lung, larynx, trachea)
Prostate cancer
Multiple myeloma
Acute and subacute peripheral neuropathy (new disease category)
Spina bifida (new disease category)
Porphyria cutanea tarda (category change in 1996)

Inadequate/Insufficient Evidence to Determine Whether an Association Exists
The available studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association. For example, studies fail to control for confounding, have inadequate exposure assessment, or fail to address latency. There is inadequate or insufficient evidence to determine whether an association exists between exposure to herbicides and the following health outcomes:

Hepatobiliary cancers
Nasal/nasopharyngeal cancer
Bone cancer
Female reproductive cancers (cervical, uterine, ovarian)
Breast cancer
Renal cancer
Testicular cancer
Leukemia
Spontaneous abortion

Inadequate/Insufficient Evidence to Determine Whether an Association Exists

Birth defects (other than spina bifida)
Neonatal/infant death and stillbirths
Low birthweight
Childhood cancer in offspring
Abnormal sperm parameters and infertility
Cognitive and neuropsychiatric disorders
Motor/coordination dysfunction
Chronic peripheral nervous system disorders
Metabolic and digestive disorders (diabetes, changes in liver enzymes,
lipid abnormalities, ulcers)
Immune system disorders (immune suppression and autoimmunity)
Circulatory disorders
Respiratory disorders
Skin cancer (category change in 1996)

Limited/Suggestive Evidence of No Association
Several adequate studies, covering the full range of levels of exposure that human beings are known to encounter, are mutually consistent in not showing a positive association between exposure to herbicides and the outcome at any level of exposure. A conclusion of "no association" is inevitably limited to the conditions, level of exposure, and length of observation covered by the available studies. In addition, the possibility of a very small elevation in risk at the levels of exposure studied can never be excluded. There is limited/suggestive evidence of no association between exposure to herbicides and the following health outcomes:

Gastrointestinal tumors (stomach cancer, pancreatic cancer, colon cancer, rectal cancer)
Bladder cancer
Brain tumors


* NOTE: "Herbicides" refers to the major herbicides used in Vietnam: 2,4-D (2,4-dichlorophenoxyacetic acid); 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) and its contaminant TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin); cacodylic acid; and picloram. The evidence regarding association is drawn from occupational and other studies in which subjects were exposed to a variety of herbicides and herbicide components.

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