Bolt H M, Filser J G
Environ Health Perspect. 1977 Dec;21:107-12. doi: 10.1289/ehp.7721107.
Rats have been exposed in a closed system to the chlorinated ethylenes vinyl chloride and trichloroethylene and to carbon tetrachloride as a reference compound. Data of uptake of the compounds, of urinary excretion of metabolites, and of exhalation after exposure show that the chlorinated ethylenes are metabolized much faster than carbon tetrachloride, probably due to their common ethylene structure. To eliminate differences in uptake, calculation of metabolites of the three compounds in tissues was based on the amount actually taken up by the animals. Vinyl chloride, trichloroethylene, and carbon tetrachloride showed irreversible binding of metabolites to tissue proteins, mainly of the liver. Irreversible protein binding of either of these compounds ranged within the same order of magnitude, if related to the amount of compound which had been taken up. Also, no differences in the relative portion of irreversibly bound metabolites were found after exposure to different atmospheric concentrations of the three compounds. As already shown for vinyl chloride, trichloroethylene is metabolized in vitro by rat liver microsomes in presence of NADPH-regenerating system to intermediates that irreversibly bind to proteins. Albumin (bovine and rabbit) was a preferred target for binding. In contrast to vinyl chloride, significant irreversible binding of trichloroethylene metabolites also occurred to non-SH-proteins (gamma-globulin, concanavalin A) and to polylysine. Hence it should be inferred that, unlike vinyl chloride, trichloroethylene metabolites not only bind to sulfhydryl groups but also, to a lesser extent, to free amino groups of proteins.
大鼠在封闭系统中接触了氯化乙烯类化合物氯乙烯和三氯乙烯，并接触了作为参考化合物的四氯化碳。有关这些化合物的摄取、代谢物的尿排泄以及接触后的呼气数据表明，氯化乙烯类化合物的代谢速度比四氯化碳快得多，这可能是由于它们具有共同的乙烯结构。为了消除摄取差异，计算组织中这三种化合物的代谢物时是基于动物实际摄取的量。氯乙烯、三氯乙烯和四氯化碳的代谢物与组织蛋白（主要是肝脏中的蛋白）表现出不可逆结合。如果与摄取的化合物量相关，这些化合物中任何一种的不可逆蛋白结合都在同一数量级范围内。此外，在接触不同大气浓度的这三种化合物后，未发现不可逆结合代谢物的相对比例存在差异。正如已在氯乙烯研究中表明的那样，在存在NADPH再生系统的情况下，三氯乙烯在体外被大鼠肝微粒体代谢为与蛋白质不可逆结合的中间体。白蛋白（牛和兔）是结合的首选靶点。与氯乙烯不同，三氯乙烯代谢物与非巯基蛋白（γ球蛋白、伴刀豆球蛋白A）和聚赖氨酸也发生了显著的不可逆结合。因此可以推断，与氯乙烯不同，三氯乙烯代谢物不仅与巯基结合，而且在较小程度上还与蛋白质的游离氨基结合。
