Mercapturic acid formation is an activation and intermediary step in the metabolism of hexachlorobutadiene.
14C-hexachlorobutadiene (HCBD), a mutagenic and nephrocarcinogenic pollutant, was administered by oral gavage of 100 mg/kg to female rats, and the radioactivity in 24 hr urine pooled. The average amount of radioactivity recovered in urine was 5.4% of the total 14C-activity ingested. Solvent extraction, high performance liquid chromatography (HPLC), radio gas chromatography and gas chromatography/mass spectrometry were used for separation and identification of metabolites. After solvent extraction and HPLC four fractions were separated containing 1%, 5%, 15% and 80% of radioactivity. In the 80% fraction one metabolite was identified after derivatization and comparison with the authentic compound as the mercapturic acid of HCBD (N-acetyl-S-1,1,2,3,4-pentachlorobutadienyl)-L-cysteine). The mercapturic acid accounts for 10% of the urinary 14C-activity. In a first attempt the mutagenic potential of the mercapturic acid was determined on Salmonella typhimurium TA 100 with and without metabolic activating S9 mix. In the presence of S9 mix the mercapturic acid exerts a strong mutagenic effect which proved to be about 80 times higher than that of HCBD. The results identify the formation of the mercapturic acid via direct glutathione conjugation as an activating and intermediary step in the metabolism of hexachlorobutadiene.
D000111:Acetylcysteine / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002070:Butadienes / Q000378:metabolism* / Q000506:poisoning; D002250:Carbon Radioisotopes; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D009153:Mutagens / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D002070:Butadienes; D002250:Carbon Radioisotopes; D009153:Mutagens; C001335:hexachlorobutadiene; D000111:Acetylcysteine