A Review: Trichloroethylene Metabolites: Potential Cardiac Teratogens

• Published in: Environmental health perspectives 1998-08, Vol.106 (suppl 4), p.995-999
• Main Authors: Johnson, Paula D., Dawson, Brenda V., Goldberg, Stanley J.
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - physiopathology; Animals; Atrial heart septal defects; Chlorinated Organics; Dichloroethylenes - metabolism; Dichloroethylenes - toxicity; Dose-Response Relationship, Drug; Embryonic and Fetal Development - drug effects; Environmental Exposure; Environmental health; Female; Fetus; Heart - drug effects; Heart Defects, Congenital - chemically induced; Heart valves; Metabolites; Potable water; Pregnancy; Pregnancy Complications - chemically induced; Rats; Teratogens; Teratology; Trichloroethylene - metabolism; Trichloroethylene - toxicity; Ventricular heart septal defects
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.98106s4995

This review is of a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have reported an increased number of congenital cardiac defects when exposed to TCE or DCE during fetal development. Metabolites of TCE and DCE studied in the drinking-water exposure study include trichloroacetic acid (TCAA), monochloroacetic acid, trichloroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacetaldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart development. Rats receiving 2730 ppm TCAA in drinking water were the only metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p=0.0004 Wilcoxon test and p=0.0015 exact permutation test). Maternal and fetal variables showed no statistically significant differences between treated and untreated groups. When treated with TCAA the increased cardiac defects, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific cardiac teratogen. Further studies of drinking-water exposure and potential mechanisms of action on the developing heart are proceeding.