Metabolism of 2,4-dinitrotoluene by intestinal microorganisms from rat, mouse, and man.

Dinitrotoluene (DNT) is an industrial chemical of importance in the production of urethane foams and elastomers. The technical grade material is a hepatocarcinogen in rodents but shows sex- and species-dependent differences in potency. We have studied the pathways of metabolism of 2,4-dinitrotoluene (2,4-DNT), the major component of technical material, in the cecal microflora of male rats, female rats, male mice, and in human feces and ileal contents. 2,4-DNT was not metabolized by any of these preparations in the presence of oxygen. Under anaerobic conditions an ordered sequence of reductive metabolism was observed. The 2- and 4-nitro groups were reduced to amino groups via nitroso intermediates which were identified by GC-MS. The reduction of the nitroso intermediate to the amino compound is presumed to involve a hydroxylamino intermediate which could not be isolated. The aminonitro compounds were then reduced to diaminotoluene. No intermediates in this sequence could be isolated. No sex- or species-dependent differences in the pathways of metabolism were observed and only small species-dependent differences in the rate of metabolism of 2,4-DNT were observed. It is concluded that the intestinal microflora of rodents represent the major site of reductive metabolism of 2,4-DNT and may play an important role in the carcinogenic action of DNT isomers.