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

Abstract

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.