Dinitrotoluene: acute toxicity, oncogenicity, genotoxicity, and metabolism.

Dinitrotoluene (DNT) is a major commodity chemical; over six hundred million pounds of DNT were used in the chemical industry in 1980. Interest in the toxicology of this important chemical was greatly increased when separate oncogenicity assays yielded the conflicting results that DNT was either not hepatocarcinogenic or produced a 100% incidence of hepatocellular carcinomas in male rats in one year. Research revealed pronounced differences in the activity of the DNT isomers and provided the reason for the dissimilar results of the various carcinogenicity studies. Cell culture genetic toxicology assays failed to predict the potent carcinogenic activity of any isomer of DNT. Only when the complex pattern of metabolic activation of DNT began to unfold and genotoxic activity was assessed in the appropriate target organ in the intact treated animal was the potent genotoxic activity of DNT revealed, and the reasons for the negative in vitro results understood. The DNTs have been extensively tested for reproductive effects in animals and humans, and the metabolism and disposition of each of the six possible isomers have been studied. This work has provided valuable information in establishing the risk of these compounds to humans.