The Agent Orange Scientific Task Force
Report on Reproductive and Developmental Effects

Task Force Members
Richard W. Clapp, M.P.H., Sc.D.
Director of Environmental Health Studies
JSI Research & Training Institute, Inc.
Boston, MA

Barry Commoner, Ph.D.
Center for the Biology of Natural Systems
Queens College, CUNY
Flushing, NY

John D. Constable, M.D.
Associate Clinical Professor of Surgery
Harvard Medical School
Boston, MA

Samuel S. Epstein, M.D.
Professor of Occupational and Environmental Medicine
University of Illinois
Chicago, IL

Peter C. Kahn, Ph.D.
Associate Professor of Biochemistry
Department of Biochemistry and Microbiology
Rutgers University
New Brunswick, NJ

James R. Olson, Ph.D.
Associate Professor
Department of Pharmacology and Therapeutics
School of Medicine and Biomedical Sciences
University of Buffalo
Buffalo, NY

David M. Ozonoff, M.D., M.P.H.
Professor and Chief, Environmental Health Section
Boston University School of Public Health
Boston, MA

Following review of the scientific literature, it is concluded that the evidence supporting the existence of a significant statistical association between exposure to phenoxyacetic acid herbicides and/or their associated contaminants (chlorinated dioxins) and reproductive and developmental effects is at least as strong as the evidence of a lack of the association. Evidence in support of this conclusion follows:

Fertility
The CDC Vietnam Experience Study (1988) found Vietnam veterans to have significantly lower mean sperm concentration and significantly lower levels of morphologically “normal” sperm than non-Vietnam veterans. Both of these parameters have traditionally been used as indicators of reduced fertility potential.

Miscarriage
The percentage of spouses’ pregnancies which resulted in miscarriages was significantly higher for Vietnam veterans than controls. Logistic regression analysis showed that Agent Orange exposure and maternal smoking were both independently and significantly associated with miscarriage in a dose-related manner (Stellman, et al., 1989). A statistically significant association between increasing herbicide exposure and miscarriage was also reported in the officer subgroup in the Air Force Study of Ranch Hand Personnel who were responsible for herbicide spraying in Vietnam (Albanese, 1988). Greater fetal loss was also reported in a population of Vietnam veterans currently living in Tasmania (Field and Kerr, 1988). Accidental exposure to TCDD in 1976 in Seveso, Italy, has also been associated with an apparent elevation in the rate of spontaneous abortions in the exposed population (Bruzzi, 1983; Bianco, et al., 1984).

Of all the Vietnamese studies, the North Vietnamese studies by Nguyen Can, et al. (1983) and Ton Duc Lang, et al. (1983, 1986) appear to have been conducted most nearly in accordance with accepted epidemiologic methods. They both support the hypothesis that paternal exposure to the components of Agent Orange (which serving in South Vietnam) can adversely affect the products of conceptions occurring considerably later (post-war North Vietnam). Nguyen Can, et al (1983) reported that elevated incidences of spontaneous abortion and congenital malformation, but not stillbirth or molar pregnancy, were associated with the father having been in South Vietnam during the war. Ton Duc Lang, et al (1983, 1986) also claimed that the degree of the father’s exposure, determined by the region of South Vietnam in which they had served, was associated with the extent to which the incidence of malformations was increased.

Birth Defects
Several studies report a higher incidence of selected birth defects in children of Vietnam veterans than controls. An Air Force study of Ranch Hand personnel, responsible for the herbicide spraying in Vietnam, reported a statistically significant increase in reported birth defects in the Ranch Hand group (Albanese, 1988). Defects reported in the Ranch Hand group included skin defects, neural tube defects, heart defects, oral clefts, and kidney defects. A preliminary analysis of medical records of children reported abnormal has also indicated that over reporting of defects may not account for the excess in birth defects in the Ranch Hand group. A recent CDC study (CDC, 1988) reported that hospital birth records did show a higher incidence of live births with cerebrospinal malformations in children of Vietnam veterans, however, the results were not statistically evaluated. Erickson, et al (1984) also reported that the risks for fathering an infant with spina bifida, cleft lip (with or without cleft palate), and “other neoplasms” such as neuroblastomas were higher for Vietnam veterans than controls. These increases were also significantly associated with increased scores on the Agent Orange Exposure Opportunity Index (Erickson, et al, 1984). An increased incidence of birth defects was also reported in a population of Vietnam veterans currently living in Tasmania (Field and Kerr, 1988). The veterans’ reproductive outcome contained significantly more children with major and minor abnormalities, tumors, chronic health problems and learning, behavioral, sensory and other relatively minor problems. Field and Kerr (1988) found three tissue systems were predominantly affected: the central nervous, the skeletal and the cardiovascular systems. Reproductive studies in North Vietnamese populations also report an association between paternal exposure to Agent Orange, while serving in South Vietnam and an elevated incidence of congenital malformation (Nguyen Can, et al., 1983; Ton Duc Lange, et. 1983 and 1986).

Additional reports of reproductive studies of populations potentially exposed to dioxins in Seveso, Italy and in Midland Country Michigan suggest the possibility of increased incidences of birth defects. A suggestive increase in the rates of certain birth defects (angioma, CNS defects, hypospadius, hip dislocation, defects of the digestive tract) has been reported in the Seveso population potentially exposed to dioxin (Bruzzi, 1983; Bianco, et al, 1984). The Michigan Department of Health (MPPH, 1983) examined the rates of birth defects in Midland County. For the period from 1970 to 1975, significantly elevated rates were reported for hip dislocations, cleft lip with or without cleft palate, hypospadius and epispadias relative to the rate in the state as a whole. In a subsequent investigation of the potential association between exposure to trichlorophenol and its associated chlorinated dioxin contaminants and birth defects, Lock, et al (1984) investigated birth outcomes in 29 trichlorophenol-producing counties in the United States. The rates of hip dislocation without CNS involvement and atrial septal defects were significantly elevated in 6 of 29 trichlorophenol-producing counties.

In summary, elevated incidences of specific birth defects have been found in several studies. Elevated rates of hypospadias, oral clefts, cardiovascular defects and hip dislocations have been reported in more than one study and are thus suggestive of an association between these defects and exposure to phenoxy herbicides, chlorophenols and their associate dioxin contaminants. Definitive interpretation of the assembled data on the reproductive toxicity of these substances in humans is constrained by the limited power of the studies to detect modest increases in detrimental effects; inadequate characterization of actual exposure and possible biases in reporting of adverse effects.