Freundt K J, Macholz J
Toxicology. 1978 Jun;10(2):131-9. doi: 10.1016/0300-483x(78)90063-x.
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.
在成年雌性Wistar大鼠中，单次8小时暴露于200 ppm（工作场所卫生标准）的反式-1,2-二氯乙烯（t-DCE）或顺式-1,2-二氯乙烯（c-DCE），会导致己巴比妥睡眠时间、唑沙仑麻痹时间显著增加，以及氨基比林代谢生成4-氨基安替比林的量显著增加。更高的二氯乙烯浓度会导致这些效应呈剂量依赖性且显著增强，c-DCE的效应强于t-DCE。在对分离的大鼠肝微粒体进行酶动力学测量的过程中，t-DCE被证明是氨基比林氧化N-脱甲基化和对硝基苯甲醚O-脱甲基化的竞争性抑制剂。从结果得出结论，肝脏药物代谢的抑制是由两种二氯乙烯异构体与混合功能氧化酶系统的竞争性和可逆相互作用引起的，这种相互作用可能发生在I型结合位点。
