Metabolism of14C-dichloroethyne in rats

Autor: D. Henschler, Michael Koob, Wolfgang Kanhai, Wolfgang Dekant
Rok vydání: 1991
Předmět:
Zdroj: Xenobiotica. 21:905-916
ISSN: 1366-5928
0049-8254
DOI: 10.3109/00498259109039530
Popis: 1. The metabolism of 14C-dichloroethyne was studied in rats by inhalation in a dynamic nose-only exposure system. 14C-Dichloroethyne was generated in 95-99% yield from 14C-trichloroethene by alkaline dehydrochlorination. 2. After inhalation of 20 ppm and 40 ppm dichloroethyne for 1 h, the retention rates were 17.6% and 15.6% of the radioactivity introduced into the exposure system, respectively. During the period of observation (96 h), almost quantitative elimination of the dose was observed. Elimination with urine accounted for 60.0% (40 ppm) and 67.8% (20 ppm) of absorbed radioactivity and elimination with faeces for 27% (40 ppm) and 27.7% (20 ppm), 3.4-3.5% remained in the carcasses. 3. Metabolites of dichloroethyne identified are: N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, dichloroethanol, dichloroacetic acid, oxalic acid and chloroacetic acid in urine; N-acetyl-S-(1,2-dichlorovinyl-L-cysteine in faeces. 4. In bile of rats exposed to 40 ppm of dichloroethyne, S-(1,2-dichlorovinyl)glutathione was the only metabolite identified. Biliary cannulation did not influence the renal excretion of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, indicating that glutathione conjugate formation occurs in the kidney. 5. The results suggest that two metabolic pathways are operative in dichloroethyne metabolism in vivo. Cytochrome P450-dependent oxidation represents a minor pathway accounting for the formation of 1,1-dichloro compounds after chlorine migration. The major pathway is the biosynthesis of toxic glutathione conjugates. Organ-specific toxicity and carcinogenicity of dichloroethyne is due most likely to the topographical distribution of gamma-glutamyl transpeptidase which is concentrated mainly in the kidney in rats.
Databáze: OpenAIRE
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