Inhibition of mixed function oxidases in rat liver by trans- and cis-1,2-dichloroethylene

A single 8-h exposure to trans-1,2-dichloroethylene (t-DCE) or cis-1,2-dichloroethylene (c-DCE) at 200 ppm (hygienic standard in workplaces) resulted in a significant increase in the hexobarbital sleeping time, the zoxazolamine paralysis time, and the metabolic formation of 4-aminoantipyrine from aminopyrine in adult female Wistar rats. Higher DCE concentrations caused a dose-dependent and substantial enhancement of these effects, the effects of c-DCE being stronger than that of t-DCE. In the course of enzyme-kinetic measurements in isolated rat liver microsomes, t-DCE proved to be a competitive inhibitor of the oxidative N-demethylation of aminopyrine and of the O-demethylation of p-nitroanisole. It is concluded from the results that the inhibition of hepatic drug metabolism is caused by a competitive and reversible interaction of the 2 DCE isomers with the mixed-function oxidase system, the interaction possibly operating at the type I binding site.