Carcinogenesis Bioassay of 2,6-Dichloro-p-Phenylenediamine (CAS No. 609-20-1) in F344 Rats and B6C3F1 Mice (Feed Study).
A carcinogenesis bioassay of 2,6-dichloro-p-phenylenediamine, a chemical intermediate, was conducted in groups of 50 F344 rats and B6C3F1 mice of either sex. Male rats were fed diets containing 1,000 or 2,000 ppm 2,6-dichloro-p-phenylenediamine and female rats were fed 2,000 or 6,000 ppm for 103 weeks. Mice were fed 1,000 or 3,000 ppm of the test chemical for 103 weeks and observed for an additional 8 weeks. Controls consisted of 50 untreated rats and 50 untreated mice of each sex. Throughout the study, mean body weights of dosed rats and mice of either sex were lower than those of the corresponding controls. A dose-related weight gain depression was particularly pronounced for rats. Ectopic hepatocytes were observed at an increased incidence in the pancreas and nephrosis was observed in increased severity in dosed rats of either sex when compared with the corresponding controls. No increase in any tumor type was observed in treated male or female rats when compared to controls. Increased incidences of liver tumors were observed in mice of both sexes. In male mice, the incidence of hepatocellular adenomas exhibited a significant positive dose-related trend (P=0.002), and the increased incidence of hepatocellular adenomas was statistically significant in the high-dose group(4/50, 7/50, 15/50: P=0.005). The combined incidence of hepatocellular adenomas and carcinomas showed a significant positive dose-related trend (P=0.004) and was statistically significant in the high-dose group (16/50, 19/50, 29/50: P=0.008). In female mice, hepatocellular carcinomas exhibited a significant positive dose-related trend (P=0.025), but no single dose group had a statistically significant increased incidence of either adenomas (4/50, 4/50, 9/50; high-dose effect: P=0.12) or carcinomas (2/50, 2/50, 7/50; high-dose effect: P=0.08) alone. When the incidences of hepatocellular adenomas and carcinomas were combined (6/50, 6/50, 16/50), these data gave a positive dose-related trend (P=0.004) and were statistically significant in the high-dose group (P=0.014). Under the conditions of this bioassay, 2,6-dichloro-p-phenylenediamine was carcinogenic for male and female B6C3F1 mice, causing increased incidences of combined hepatocellular adenomas and carcinomas, and for male B6C3F1 mice, causing an increased incidence of hepatocellular adenomas alone. 2,6-Dichloro-p-phenylenediamine was not carcinogenic for male or female F344 rats. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive