Intestinal metabolism of 2,4-dinitrotoluene in rats.

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. The pathways of metabolism of 2,4-DNT in the cecal microflora of rats were studied. 2,4-DNT was not metabolized by this preparation in the presence of O2. Under anerobic conditions, an ordered sequence of reductive metabolism was observed. 2,4-DNT was reduced to 2-amino-4-nitroluene (2A4NT) and 4-amino-2-nitrotoluene (4A2NT) via 2-hydroxylamino-4-nitrolouene (2HA4NT) and 4-hydroxylamino-2-nitrotoluene (4HA2NT), which were identified by mass spectral (MS) comparison with authentic materials. The 2 aminonitrotoluenes were then reduced to 2,4-DAT. No intermediates in this sequence could be isolated. Rat intestinal microflora catalyze the reductive metabolism of 2,4-DNT and the reduction of 2,4-DNT to 2,4-DAT may play a role in the carcinogenicity of 2,4-DNT.