CARDIAC TERATOGENESIS OF HALOGENATED HYDROCARBON CONTAMINATED DRINKING-WATER

Objectives. The purpose of this study was to test the hypothesis that administration of trichloroethylene and dichloroethylene to pregnant rats during organogenesis would produce a significant fetal cardiac teratogenic effect. It was also hypothesized that administration of these compounds only before pregnancy would not be associated with fetal cardiac teratogenesis. Background. Epidemiologic observations demonstrated an increased number of congenital cardiac defects in children whose mother resided in an area with drinking water contaminated by trichloroethylene and dichloroethylene. A prior provocative intrauterine exposure study in rats established a positive link between these contaminants and an increased number of fetal hearts with congenital cardiac defects. Methods. Sprague-Dawley rats were given pure tap drinking water (control subjects) or water contaminated with high or low dose of trichloroethylene or dichloroethylene (experimental groups) during prepregnancy only, prepregnancy and pregnancy or during pregnancy alone. Results. A total of 2,045 fetuses were examined. Trichloroethylene or dichloroethylene delivered exclusively in the period before pregnancy caused no increase in congenital cardiac malformations over the control level. Compared with the control group, rats exposed to these agents both before and during pregnancy, had a significantly greater number of fetuses with congenital cardiac malformations. Trichloroethylene (high dose only) administered only during pregnancy produced a significant increase in cardiac defects. Other fetal variables, including noncardiac congenital abnormalities, showed no significant difference between control and treated groups. Conclusions. Trichloroethylene and dichloroethylene administered during organogenesis are cardiac, but not general, teratogens. The data indicate that these agents administered in drinking water to pregnant rats caused an increased number of congenital cardiac defects in rat fetuses.