4-Chloro-m-phenylenediamine, an intermediate in the preparation of dyes, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer reported among workers in the dye manufacturing industry.
A bioassay of 4-chloro-m-phenylenediamine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 4-Chloro-m-phenylenediamine was administered in the feed, at either of two concentrations, to groups of 49 or 50 male and 50 female animals of each species. The dietary concentrations of 4-chloro-m-phenylediamine used in the chronic bioassay for low and high dose rats were 0.2 and 0.4 percent, respectively. The time-weighted average dietary concentrations used for low and high dose mice were 0.7 and 1.4 percent, respectively. After a 78-week period of compound administration, observation of the rats continued for an additional 17 weeks. For each species, 50 animals of each sex were placed on test as untreated controls.
In both species, adequate numbers of animals in all groups survived long enough to be at risk from late-developing tumors.
Among male rats, an increased incidence of adrenal pheochromocytomas was statistically associated with dosage of 4-chloro-m-phenylenediamine. The incidence of these tumors was significantly higher in the high dose group than in the control group.
Among female mice, there was a significant increased incidence of hepatocellular carcinomas in the low dose group and a significantly combined incidence of hepatocellular carcinomas and hepatocellular adenomas in both low and high dose groups as compared to controls.
No other neoplasms in either species were considered to be related to compound administration.
Under the conditions of this bioassay, dietary administration of 4-chloro-m-phenylenediamine was carcinogenic to the experimental animals, causing an increased incidence of hepatocellular tumors in female B6C3F1 mice and an increased incidence of adrenal pheochromocytomas in male Fischer 344 rats.