p-Chloroaniline, a dye and chemical intermediate, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer observed among dye manufacturing industry workers.
A bioassay for the possible carcinogenicity of p-chloroaniline was conducted using Fisher 344 rats and B6C3F1 mice. p-Chloroaniline 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 p-chloroaniline were, respectively, 500 and 250 ppm for rats and 5000 and 2500 ppm for mice. The compound was administered in the diet for 78 weeks, followed by an observation period of 24 weeks for rats and 13 weeks for mice.
There were no significant positive associations between the dietary concentrations of p-chloroaniline administered and mortality in female rats or in mice of either sex; however, there was a significantly positive association between concentration and mortality in male rats. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, in relation to controls, was observed in high dose female rats and dosed mice of both sexes, indicating that the concentration of p-chloroaniline administered to these animals may have approximated the maximum tolerated concentrations. Although splenic lesions were observed in male rats, no mean body weight depression relative to controls was associated with administration of p-chloroaniline to these animals. Therefore, it is possible that these animals may have been able to tolerate a higher dietary concentration of the compound.
The only neoplastic lesions found that might be related to administration of the compound were mesenchymal tumors in the spleens of male rats and hemangiomatous tumors in mice. In male rats, there was a significant positive association between compound administration and the incidences of fibroma or fibrosarcoma of the spleen. Theincidences of these tumors were not significantly elevated when compared to those in control rats, but the rarity of these tumors in male Fisher 344 rats (0/360 in historical male control rats in this laboratory) strongly suggests a chemically related effect. In addition, three sarcomas of other types were found in high dose male rats. In mice of both sexes, hemangiomas and hemangiosarcomas were found at elevated incidences, when compared to control mice, in the spleen, liver, kidney, and multiple body sites. The increased incidences in dosed mice were statistically related to dose but were not statistically significant when compared directly to matched control animals. In comparison to historical control data, the incidences of hemangiomatous tumors in the dosed mice were elevated, but not greatly. The evidence was considered insufficient to conclusively relate the hemangiomatous tumors in mice to compound administration. Nonneoplastic proliferative and chronic inflammatory lesions were also found in the spleens of dosed rats and mice.
The findings of small numbers of fibromas and sarcomas in the spleens of male rats was considered strongly suggestive of carcinogenicity because of the rarity of these tumors in the spleens of control rats. Hemangiomatous tumors in dosed mice may also have been associated with administration of p-chloroaniline. However, it is concluded that, under the conditions of this bioassay, sufficient evidence was not found to establish the carcinogenicity of p-chloroaniline for Fisher 344 rats or B6C3F1 mice.