Abstract
2, 4-Dinitrotoluene (2, 4-DNT), which is an industrial chemical of importance in the production of urethane foams and elastomers, is a hepatocarcinogen in rats. 2, 4-Diaminotoluene (2, 4-DAT), one of the urinary and hepatic metabolites of 2, 4-DNT, is also carcinogenic in rats. We have studied the pathways of metabolism of 2, 4-DNT in the cecal microflora of rats. 2, 4-DNT was not metabolized by this preparation in the presence of oxygen. Under anaerobic conditions, an ordered sequence of reductive metabolism was observed. 2, 4-DNT was reduced to 2-amino-4-nitrotoluene (2A4NT) and 4-amino-2-nitrotoluene (4A2NT) via 2-hydroxylamino-4-nitrotoluene (2HA4NT) and 4-hydroxylamino-2-nitrotoluene (4HA2NT), which were identified by mass spectral (MS) comparison with authentic materials. The two aminonitrotoluenes were then reduced to 2, 4-DAT. No intermediates in this sequence could be isolated. These findings indicate that rat intestinal microflora catalyze the reductive metabolism of 2, 4-DNT and suggest that the reduction of 2, 4-DNT to 2, 4-DAT may play a role in the carcinogenicity of 2, 4-DNT.
