Aniline hydrochloride, a dye intermediate and a commercially important salt of aniline, was selected for bioassay by the National Cancer Institute because of the increased incidence of bladder cancer among workers in the dye manufacturing industry and the historical association of aromatic amines with this increased cancer risk.
A bioassay of aniline hydrochloride for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Aniline hydrochloride was administered in the feed, at either of two concentrations, to groups of 50 male and female animals of each species, with the exception of 49 female mice in the high dose group. The high and low dietary concentrations of aniline hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.2 and 0.6 percent for mice. After a 103-week period of compound administration, observation of the rats and mice continued for up to an additional 5 weeks.
For rats and mice, respectively, 25 and 50 animals of each sex were placed on test as controls and fed only the basal diet.
In male rats there were several types of mesenchymal tumors, primarily of the spleen, associated with administration of the compound. Hemangiosarcomas of the spleen and the combined incidence of fibrosarcomas and sarcomas NOS of the spleen were each statistically significant in male rats. The combined incidence of fibrosarcomas and sarcomas NOS of multiple body organs was also significant in male rats. The number of female rats having fibrosarcomas or sarcomas NOS of either the spleen alone or multiple organs of the body cavity was significantly associated with increased dietary concentration of aniline hydrochloride. This result was not supported by the Fischer exact tests, but because of the rarity of these tumors, the observed incidences (0/24 in the control group, 1/50 [2 percent] in the low dose group, 7/50 [14 percent] in the high dose group) were considered indicative of a compound-related carcinogenic effect.
In mice of both sexes no tumors occurred in statistically significant increased incidences among dosed groups when compared to controls.
Under the conditions of this bioassay, dietary administration of aniline hydrochloride was carcinogenic to male and female Fischer 344 rats, inducing hemangiosarcomas and a combination of fibrosarcomas and sarcomas NOS of the spleen and a combination of fibrosarcomas and sarcomas NOS of multiple body organs. There was no evidence of compound-induced carcinogenicity in B6C3F1 mice of either sex.