Dinitrotoluene isomer-specific hepatocarcinogenesis in F344 rats

The hepatocarcinogenicity of 2,4-dinitrotoluene [(2,4-DNT) CAS: 121-14-2], 2,6-DNT (CAS: 606-20-2), and a representative technical-grade DNT (TDNT) containing 76% 2,4-DNT and 18% 2,6-DNT was studied in male F344 rats. Rats were fed diets containing 2,4-DNT, 2,6-DNT, or TDNT at concentrations that resulted in doses of 27 mg/kg/day for 2,4-DNT, 7 or 14 mg/kg/day for 2,6-DNT, and 35 mg/kg/day for TDNT. The carcinogenic effects were evaluated after 1 year of treatment. Administration of 2,6-DNT produced hepatocellular carcinomas in 100 and 85% of animals receiving 14 and 7 mg/kg, respectively. In contrast to the 2,6-DNT results, feeding of 2,4-DNT for 1 year caused no hepatic tumors. Treatment with both isomers (TDNT) resulted in a 47% incidence of hepatocellular tumors. The majority of tumors had a trabecular pattern, and pulmonary metastases were present in the 14- and 7-mg/kg 2,6-DNT-fed groups. These results have demonstrated that 2,6-DNT is a potent and complete hepatocarcinogen and that 2,4-DNT, under these conditions, is nonhepatocarcinogenic. In addition, these data indicate that 2,6-DNT accounts for the majority of the carcinogenic activity of TDNT.