Bioassay of 2,6-Toluenediamine Dihydrochloride for Possible Carcinogenicity (CAS No. 15481-70-6).

2,6-Toluenediamine is used as an intermediate in the production of dyes for furs and textiles, and of flexible polyurethane foams and elastomers. A bioassay of 2,6-toluenediamine dihydrochloride for possible carcinogenicity was conducted by feeding diets containing the test chemical to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were fed the test chemical at two doses, 250 or 500 ppm, for 103 weeks and observed for 1 additional week. Groups of 50 mice of each sex were fed the test chemical at two doses, 50 or 100 ppm, for 103 weeks and then observed for 1 additional week. Groups of 50 untreated rats and 50 untreated mice of each sex were used as matched controls. All surviving animals were killed and necropsied at 104 weeks. Weight gain depression was less than 10% for dosed groups of male rats and male and female mice, when compared with controls. Mean body weight gain was depressed 17% in low-dose female rats and 27% in high-dose female rats. Mortality was not increased in rats or mice of either sex by the test chemical. No clinical evidence indicated that mice of either sex received a maximum tolerated dose of the compound. In male rats, islet-cell adenomas of the pancreas and neoplastic nodules or carcinomas of the liver occurred in dose-related trends that were significant using the Cochran-Armitage test (P=0.025 and P=0.037, respectively). The results of the Fisher exact test were not significant for either lesion. The occurrences of tumors in dosed female rats were not significantly different from those in control rats. Significant results in the negative direction were observed in the incidences of C-cell tumors of the thyroid in male rats and of fibroadenomas of the mammary gland in female rats. In male mice, in the low-dose group, lymphomas occurred at an incidence significantly higher (P=0.046) than that of the corresponding control group; however, the incidence was not significant when the Bonferroni criterion for multiple comparison was used. The occurrence of hepatocellular carcinomas in female mice was dose related, but the result of the Fisher exact test comparing the incidence in the high-dose group with that in the controls was not significant. It was concluded that, under the conditions of the bioassay, 2,6-toluenediamine dihydrochloride was not carcinogenic for male and female F344 rats or for male and female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative