Metabolism of 14C-dichloroethyne in rats.
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.
Kanhai
W
W
Institut für Toxikologie, Universität Würzburg, Germany.
Koob
M
M
Dekant
W
W
Henschler
D
D
D000114:Acetylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000280:Administration, Inhalation; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D007668:Kidney / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
C002978:dichloroacetylene; D000114:Acetylene