2-Methyl-1-nitroanthraquinone, an intermediate in the synthesis of anthraquinone dyes, was selected for bioassay by the National Cancer Institute in an attempt to elucidate those chemicals which may be responsible for the increased incidence of bladder cancer among workers in the dye manufacturing industry. Aromatic nitro compounds are one of several classes of chemicals thought to contribute to the increased cancer risk in this industry.
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 betweenincreased 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.