Studies on benzyl acetate. II. Use of specific metabolic inhibitors to define the pathway leading to the formation of benzylmercapturic acid in the rat.
Specific metabolic inhibitors were used to define the route of metabolism of benzyl acetate leading to the formation of benzylmercapturic acid. Male Fischer 344 rats were dosed by gavage with [methylene-14C]benzyl acetate (500 mg/kg) alone or together with pyrazole (200 mg/kg), pentachlorophenol (10 mg/kg) or both pentachlorophenol (10 mg/kg) and pyrazole (200 mg/kg), given in each case ip. Urine and faeces were collected and urinary metabolites were assayed by radio-TLC and HPLC. The excretion of 14C was rapid in all cases, with most of the dose excreted in the urine within 24 hr. Co-administration of pyrazole (an inhibitor of alcohol dehydrogenase) with benzyl acetate caused an 11-fold increase in the excretion of benzylmercapturic acid and halved the percentage of the dose excreted as benzoyl glucuronide. Pretreatment with pentachlorophenol, an inhibitor of sulphotransferase activity in vivo, abolished the excretion of benzylmercapturic acid, while excretion of the mercapturate following treatment with both pyrazole and pentachlorophenol was higher than in control or pentachlorophenol-treated rats, but much lower than in the animals given pyrazole alone. Taken together, these results suggest very strongly that the formation of benzylmercapturic acid involves the sulphate ester of benzyl alcohol as an obligatory intermediate and does not appear to involve a metabolic intermediate with sufficient reactivity to have toxicological relevance.
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D001593:Benzyl Compounds / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D010416:Pentachlorophenol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D001593:Benzyl Compounds; D011720:Pyrazoles; C046412:benzyl acetate; C031280:pyrazole; D010416:Pentachlorophenol; D000111:Acetylcysteine; C029319:S-benzyl-N-acetyl-L-cysteine