Studies in detoxication. 34. The metabolism of chlorobenzene in the rabbit. Isolation of dihydrodihydroxychlorobenzene, p-chlorophenylglucuronide, 4-chlorocatechol glucuronide and p-chlorophenylmercapturic acid

Abstract

Chlorobenzene was shown to undergo "perhydroxylation" in the rabbit by isolation of crystalline 3,4-dihydro-3,4-dihydroxychlorobenzene (yield, 0.03%), the structure of which was proved spectrophoto-metrically by conversion to p-chlorophenol. The rate of dehydration of the diol by acid was studied spectrophotometrically and the process shown to be a monomolecular reaction. p-Chlorophenylmercapturic acid was isolated, and its optical rotation and absorption spectrum recorded. The main metabolite of chlorobenzene is 4-chlorocatechol which was isolated from the ethereal sulfate fraction and as its glucuronide, 4-chloro-2-hydroxyphenylglucuronide. p-Chlorophenol and its glucuronide were also isolated, but were very minor metabolites of chlorobenzene amounting to about 0.5% of the dose. The above findings have been discussed and a hypothesis presented relating mercapturic acid formation with oxidation during chlorobenzene metabolism.