A bioassay of
2-methyl-1-nitroanthraquinone for possible carcinogenicity was conducted using Fischer 344 rats.
2-Methyl-1-nitroanthraquinone was administered in the feed at either of two concentrations to groups of 50 male and 50 female animals. The high and low dietary concentrations used were 0.12 and 0.06 percent, respectively, for the male and female rats. After a 78-week treatment period, observation of the rats continued for an additional 31 weeks. Fifty rats of each sex were placed on test as controls. No
2-methyl-1-nitroanthraquinone was added to their diet. Survival in both the male and female rats was adequate for a meaningful statistical analysis of late-developing
tumors; however, there was a significant positive association between increased dosage and elevated mortality in female rats.
Hepatocellular carcinomas and neoplastic nodules of the liver occurred in both the male and female treated rats. A statistically significant association between increased dosage and an elevated incidence of
hepatocellular carcinomas was indicated by the Cochran-Armitage test for the males (1/48, 5/48, and 9/49 in control, low dose, and high dose, respectively); however, the Fisher exact tests supported these results only for the high dose males. The incidence of neoplastic nodules was statistically significant in the male rats (0/48, 2/48, and 6/49 in control, low dose, and high dose, respectively), as indicated by the Cochran-Armitage test and supported by the Fisher exact test for the high dose group. When those rats having either
hepatocellular carcinomas or neoplastic nodules of the liver were combined and evaluated simultaneously, the Cochran-Armitage tests indicated statistically significant associations between increased dosages and elevated
tumor incidences in both the males and females. This was supported by the Fisher exact tests for males but not for females. The incidences of one
tumor type, subcutaneous
fibroma, were found to be statistically significant in both male and female rats. No other
tumors occurred in treated animals in statistical]y significant incidences when compared to controls.
Squamous-cell papillomas and
squamous cell carcinomas of the forestomach were observed only in high dose rats. Although the incidences of these gastric
tumors were not statistically significant, historical data indicate that these
tumors are rare in Fischer 344 rats. The occurrence of these
tumors in high dose rats, together with the frequent occurrence of nonneoplastic proliferative lesions of the forestomach in treated rats, indicates that the occurrence of these
tumors was related to administration of
2-methyl-1-nitroanthraquinone. An increased incidence of
bladder tumors (
papillomas, transitional-cell
papillomas, and
sarcomas) was observed among female rats. Under the conditions of this bioassay, the results indicate that orally administered
2-methyl-1-nitroanthraquinone is carcinogenic in male Fischer 344 rats, producing
hepatocellular carcinomas. Increased incidences of subcutaneous
fibromas in both male and female Fischer 344 rats were also associated with the administration of the compound.
Tumors of the forestomach and bladder in these animals may also have been related to the administration of the test chemical.