Bioassay of 2-nitro-p-phenylenediamine for possible carcinogenicity.

A bioassay for the possible carcinogenicity of 2-nitro-p-phenylenediamine was conducted using Fischer 344 rats and B6C3F1 mice. 2-Nitro-p-phenylenediamine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of 2-nitro-p-phenylenediamine were, respectively, 1,100 and 550 ppm for male rats, 2,200 and 1,100 ppm for female rats, and 4,400 and 2,200 ppm for mice of both sexes. The compound was administered in the diet for 78 weeks, followed by an observation period of 27 weeks for rats and 12 to 13 weeks for mice. There were no significant positive associations between the dietary concentrations of 2-nitro-p-phenylenediamine administered and mortality in rats and mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, relative to controls, was observed in dosed rats and mice of both sexes, indicating that the concentrations administered to these animals may have approximated the maximum tolerated dosages. When the female mice in each group, having hepatocellular carcinoma or hepatocellular adenoma, were combined and the resulting incidences statistically analyzed, there was a significant positive association between concentration administered and the incidence of these tumors. This finding was supported by a significant high dose to control Fisher exact comparison. No tumors occurred in statistically significant increased incidences when dosed male or female rats or male mice were compared to their respective controls. Under the conditions of this bioassay, dietary administration of 2-nitro-p-phenylenediamine was carcinogenic to female B6C3F1 mice, causing an increased incidence of hepatocellular neoplasms, primarily hepatocellular adenomas. There was no convincing evidence for the carcinogenicity of the compound in Fischer 344 rats or in male B6C3F1 mice.