A REVIEW - TRICHLOROETHYLENE METABOLITES - POTENTIAL CARDIAC TERATOGENS

This review is of a series of the authors' studies designed to test th e hypothesis that administration of trichloroethylene (TCE), dichloroe thylene (DCE), their metabolites, and related compounds are responsibl e for fetal cardiac teratogenesis when given to pregnant rats during o rganogenesis. identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health ri sks. Epidemiologic studies and previous teratogenic studies using chic k embryos and fetal rats have reported an increased number of congenit al cardiac defects when exposed to TCE or DCE during fetal development . Metabolites of TCE and DCE studied in the drinking-water exposure st udy include trichloroacetic acid (TCAA), monochloroacetic acid, trichl oroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacet aldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart d evelopment. Rats receiving 2730 ppm TCAA in drinking water were the on ly metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p=0.0004 Wilcoxo n test and p=0.0015 exact permutation test). Maternal and fetal variab les showed no statistically significant differences between treated an d untreated groups. When treated with TCAA the increased cardiac defec ts, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific ca rdiac teratogen. Further studies of drinking-water exposure and potent ial mechanisms of action on the developing heart are proceeding.