Studies in detoxication. 40. The metabolism of nitrobenzene in the rabbit. o-, m- and p-Nitrophenols, o-, m- and p-aminophenols and 4-nitrocatechol as metabolites of nitrobenzene

Abstract

Nitrobenzene undergoes extensive reduction in vivo and at dose levels of 150-200 mg./kg. about 55% is excreted as metabolites in the urine during 2 days after feeding; 20% is in the form of nitro compounds and 35% as amino compounds, mainly p-aminophenol derivatives. Small amts. of nitrobenzene metabolites are excreted for a week after dosing, and appreciable amts. of nitrobenzene can be detected in the fat of the animal 2 days after dosing. The nitro compounds found in the urine were nitrobenzene and o-nitrophenol, which occurred in very small amts., m- and p-nitrophenol, which occurred in relatively large amts., and 4-nitrocatechol. The last 3 phenols were isolated by partition chromatography on silica. The amino compounds found were aniline, o- and m-aminophenol each amounting to about 0.5% of the dose, and p-aminophenol which was the main metabolite (35%). The o- and p-aminophenols were isolated. Paper chromatography of the aminophenols was studied using wet isopropyl ether as solvent. All the phenols excreted were conjugated. The results suggest that the main path of nitrobenzene metabolism is through phenylhydroxylamine to p-aminophenol. The results were also discussed in relation to the perhydroxylation and free radical hypotheses of aromatic hydroxylation in vivo.