Species differences in the biotransformation of ethyl chloride. II. GSH-dependent metabolism.

Abstract

Groups of male and female F-344 rats and B6C3F1 mice were exposed to 15,000 ppm ethyl chloride (monochloroethane, ECL) or to air for 5 days (6 h/day). In this report, features of GSH-dependent ECL metabolism in the animals are described. A concurrent report describes the features of the cytochrome P450-dependent oxidative ECL metabolism (Fedtke et al. 1994). ECL conjugation to GSH in hepatic cytosolic fractions was catalyzed by GSH S-transferases. The specific activities were 0.16 +/- 0.03 and 0.17 +/- 0.01 nmol ECL conjugated/(min mg protein) in air treated male and female F-344 rats, respectively. These activities were not significantly altered by the ECL treatment. Compared with rats, the GSH-transferase activities towards ECL were generally higher in male and female B6C3F1 mice (0.71 +/- 0.19 and 1.01 +/- 0.19, respectively) and were slightly decreased by ECL treatment. The ECL conjugation to GSH resulted in a marked reduction of the GSH concentration in the lung and the uterus after 5 days of exposure. In contrast, liver and kidney GSH concentrations were affected only to a minor degree. Formed S-ethyl-glutathione was converted to the mercapturic acid S-ethyl-N-acetyl-L-cysteine (SENACys), which was detected in the urine of both species. In addition, the non-acetylated intermediate S-ethyl-L-cysteine (SECys) was excreted in mouse urine but not in rat urine. The cumulative amounts of SENACys and SECys excreted after 5 days were up to fivefold higher in mice than in rats and the excretion kinetics were species specific.(ABSTRACT TRUNCATED AT 250 WORDS)