Studies in detoxication. 68. The metabolism of [14C]nitrobenzene in the rabbit and guinea pig

Abstract

Study was made of the fats in rabbits of nitrobenzene labeled randomly in one C atom with C14. In 30 hours the expired air contains about 1% of the dose as CO2 and 0.6% as unchanged nitrobenzene. Elimination of CO2 is not complete within this time. In 4-5 days, 58% of the nitrobenzene is eliminated in the urine. This is present as the previously established metabolites: p-aminophenol (31%), m-nitrophenol (9%), p-nitrophenol (9%), m-aminophenol (4%), o-aminophenol (3%), 4-nitrocatechol (0.7%), aniline (0.3%) and o-nitrophenol (0.1%). Two new metabolites, nitroquinol (0.1%) and p-nitro-phenylmercapturic acid (0.3%), were found in the urine. The denitration products, phenol, catechol, L-phenylmercapturic acid, and trans-muconic acid, did not occur in the urine. Nitrosobenzene, azoxybenzene, azobenzene and benzidine, the presence of which would have substantiated the occurrence of nitrosobenzene and phenylhydroxyalmine as intermediates in the formation of p-aminophenol, were not detected in the urine. The total excretion of radioactivity in the expired air, urine and feces accounting for nearly 70% of the dose of nitro-benzene is 4-5 days after dosing. The remainder is present in the tissues and is eliminated slowly as metabolites in the urine, which is still radioactive 10 days after dosing, and probably also as CO2. Two days after dosing, about 54% of the administered radioactivity was found in the tissues, particularly in the fat and the intestinal tract. Unchanged nitro-benzene was present in the tissues of this animal. Eight days after dosing, in another experiment, 8% of the radioactivity was found in the tissues, the fat being the most active. No free nitrobenzene was detected in this animal. The feces contain about 9% of the administered radioactivity, of which about 6% is present as p-aminophenol. These experiments account for 85-90% of the administered nitrobenzene.