Metabolism of 2,3-dichloro-1-propene in the rat. Consideration of bioactivation mechanisms.
At the present time, comprehensive metabolism studies of 2,3-dichloro-1-propene (2,3-DCP) have not yet been reported. We have investigated the biotransformation of 2,3-DCP using female Wistar rats in order to elucidate the bioactivation mechanisms. 175 mg/kg, 1,3-14C-2,3-DCP in corn oil was administered to a rat. The animal was killed 20 hr later. Approximately 56.7% of the radioactivity was excreted in the urine, 1.6% in the feces, 5.3% was exhaled as unchanged 2,3-DCP, and 0.3% as CO2. 31.3% remained in the organs and the carcass. Three metabolic pathways were established. 1) Conjugation with GSH leading to S-(2-chloro-2-propenyl)mercapturic acid. 2) The P450 induced epoxidation with subsequent rearrangement to highly mutagenic 1,3-dichloroacetone. 1,3-Dichloroacetone was further converted to the dimercapturic acid, 1,3-(2-propanone)-bis-S-(N-acetylcysteine). 3) The hydrolysis to 2-chloroallyl alcohol followed by alcohol dehydrogenase catalyzed formation of highly mutagenic 2-chloroacrolein. The 2-chloroallyl alcohol is excreted directly in the urine and as the glucuronide. 2-Chloroacrolein is further oxidized to 2-chloroacrylic acid which is also excreted in the urine.
D000498:Allyl Compounds / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005260:Female; D006843:Hydrocarbons, Chlorinated; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains
D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; C043065:2,3-dichloro-1-propene