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氯乙烯的作用机制数据与风险评估:DNA反应活性及跨物种定量风险外推

Vinyl chloride mechanistic data and risk assessment: DNA reactivity and cross-species quantitative risk extrapolation.

作者信息

Whysner J, Conaway C C, Verna L, Williams G M

机构信息

Toxicology and Risk Assessment Program, American Health Foundation, Valhalla, NY 10595-1599, USA.

出版信息

Pharmacol Ther. 1996;71(1-2):7-28. doi: 10.1016/0163-7258(96)00060-5.

Abstract

Vinyl chloride produced several tumor types among species. Angiosarcoma of the liver is found in all tested species, including humans with occupational exposures. Vinyl chloride is biotransformed by CYP2E1 to DNA-reactive chloroethylene oxide producing cyclic etheno adducts, which are mutagenic. The dose-response for angiosarcoma of the liver formation in rodents is supralinear, which is consistent with saturation of metabolic activation, and the tumor rate in humans at occupational exposure levels is similar to that for equivalent exposures in rodents.

摘要

氯乙烯在多种物种中引发了几种肿瘤类型。在所有受试物种中都发现了肝血管肉瘤,包括职业接触氯乙烯的人类。氯乙烯通过细胞色素P450 2E1(CYP2E1)生物转化为具有DNA反应性的环氧氯乙烯,生成环乙烯基加合物,具有致突变性。啮齿动物中肝血管肉瘤形成的剂量反应呈超线性,这与代谢活化的饱和一致,职业接触水平下人类的肿瘤发生率与啮齿动物同等接触水平下的相似。

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