EVALUATION OF THE DEVELOPMENTAL TOXICITY OF TRICHLOROETHYLENE AND DETOXIFICATION METABOLITES USING XENOPUS

Potential mechanisms of trichloroethylene-induced developmental toxici ty were evaluated using FETAX (Frog Embryo Teratogenesis Assay-Xenopus ). Early Xenopus laevis embryos were exposed to trichloroethylene for 96 h in two separate definitive concentration-response assays with and without an exogenous metabolic activation system (MAS) and inhibited MAS. The MAS was treated with either carbon monoxide or cyclohexene ox ide to modulate mixed-function oxidase (MFO) or epoxide hydrolase acti vity, respectively. Trichloroethylene metabolites: dichloroacetic acid , trichloroacetic acid, trichloroethanol, and oxalic acid were also ev aluated in two separate definitive, static renewal tests. Addition of the MAS decreased the 96 h LC50 and EC50 (malformation) of trichloroet hylene 1.8-fold and 3.8-fold, respectively. Addition of the carbon mon oxide inhibited MAS decreased the developmental toxicity of activated trichloroethylene to levels approximating that of the parent compound. Cyclohexene oxide-inhibited MAS substantially increased the developme ntal toxicity of trichloroethylene. In addition, each of the metabolit es tested were significantly less developmental toxic than the parent compound, trichloroethylene. Results indicate that a highly embryotoxi c epoxide intermediate, trichloroethylene oxide, formed as the results of MFO mediated metabolism may play a significant role in the develop mental toxicity of trichloroethylene in vitro.