p-Cresidine, used in the production of various azo dyes, was selected for bioassay by the National Cancer Institute in response to the high incidence of bladder cancer observed among dye manufacturing industry workers. Aromatic amines are one class of chemicals believed to contribute to the increased cancer risk in this industry.
A bioassay of p-cresidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. p-Cresidine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.5 and 1.0 percent, respectively. The time-weighted average concentrations fed to low dose male, low dose female, high dose male and high dose female mice were 0.22, 0.22. 0.46, and 0.44 percent, respectively.
All dosed animals, except for high dose male mice, were administered p-cresidine in the diet for 104 weeks and observed for an additional period of up to 2 weeks. All high dose male mice were dead by the end of week 92. For each species, 50 animals of each sex were placed on test as controls and fed only the basal laboratory diet.
Mortality rates were dose-related for both sexes of both species. That incidences of certain tumors were higher in low dose than in high dose groups was probably due to accelerated mortality in the high dose group.
In dosed rats of both sexes, statistically significant incidences of bladder carcinomas (combined incidences of papillary carcinomas, squamous-cell carcinomas, transitional-cell papillomas, transitional-cell carcinomas, and undifferentiated carcinomas) and olfactory neuroblastomas were observed. The combined incidence of neoplastic nodules of the liver, hepatocelular carcinomas, or mixed hepato/cholangio carcinomas was also significant in low dose male rats.
In both male and female dosed mice, the incidence of bladder carcinomas (combined incidence of carcinomas NOS, squamous-cell carcinomas, and transitional carcinomas) was significant. The incidence of hepatocellular carcinomas was also significant in dosed female mice.
Under the conditions of this bioassay, p-cresidine was carcinogenic to Fischer 344 rats, causing increased incidences of carcinomas and of papillomas of the urinary bladder in both sexes, increased incidences of olfactory neuroblastomas in both sexes, and of liver tumors in males. p-Cresidine was also carcinogenic in B6C3F1 mice, causing carcinomas of the urinary bladders in both sexes and hepatocellular carcinomas in females.