Abstract for TR-219

A carcinogenesis bioassay of 2,6-dichloro-p-phenylenediamine, a chemicalintermediate, was conducted in groups of 50 F344 rats and B6C3F1 mice ofeithersex. Male rats were fed diets containing 1,000 or 2,000 ppm2,6-dichloro-p-phenylenediamine and female rats were fed 2,000 or 6,000ppm for103 weeks. Mice were fed 1,000 or 3,000 ppm of the test chemical for 103weeksand observed for an additional 8 weeks. Controls consisted of 50 untreatedratsand 50 untreated mice of each sex.

Throughout the study, mean body weights of dosed rats and mice of eithersexwere lower than those of the corresponding controls. A dose-relatedweight gain depression was particularly pronounced for rats.

Ectopic hepatocytes were observed at an increased incidence in the pancreasandnephrosis was observed in increased severity in dosed rats of either sex whencompared with the corresponding controls. No increase in any tumor type wasobserved in treated male or female rats when compared to controls.

Increased incidences of liver tumors were observed in mice of both sexes. Inmale mice, the incidence of hepatocellular adenomas exhibited a significantpositive dose-relatedtrend (P=0.002), and the increased incidence of hepatocellular adenomas wasstatistically significant in the high-dosegroup(4/50, 7/50, 15/50: P=0.005). The combined incidence of hepatocellularadenomas and carcinomas showed a significant positive dose-relatedtrend (P=0.004) and was statistically significant in the high-dosegroup (16/50, 19/50, 29/50: P=0.008).

In female mice, hepatocellular carcinomas exhibited a significant positivedose-relatedtrend (P=0.025), but no single dose group had a statistically significantincreased incidence of either adenomas (4/50, 4/50, 9/50; high-doseeffect: P=0.12) or carcinomas (2/50, 2/50, 7/50; high-doseeffect: P=0.08) alone. When the incidences of hepatocellular adenomas andcarcinomas were combined (6/50, 6/50, 16/50), these data gave a positivedose-relatedtrend (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 wascarcinogenic for male and female B6C3F1 mice, causing increasedincidences ofcombined hepatocellular adenomas and carcinomas, and for male B6C3F1mice,causing an increased incidence of hepatocellular adenomas alone.2,6-Dichloro-p-phenylenediamine was not carcinogenic for male or femaleF344rats.