Chemical Formula: C7H8N2O3
5-Nitro-o-anisidine, a tri-substituted benzene derivative used as an intermediate in the synthesis of dyes, was selected for bioassay by the National Cancer Institute along with other dye intermediates in an attempt to determine which chemicals may be responsible for the increased incidence of bladder cancer observed among workers in the dye manufacturing industry. Aromatic amines and amino compounds are thought to contribute to the increased cancer risk in this industry.
A bioassay of 5-nitro-o-anisidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 5-Nitro-o-anisidine 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 0.4 and 0.8 percent, respectively. Dose A and B mice were fed dietary concentrations of 0.8 and 1.6 percent when initially placed on test, but after week 15 the concentration fed to dose B mice was reduced to 0.4 percent. After a 78-week period of chemical administration, observation of rats continued for up to an additional 28 weeks and observation of mice continued for up to an additional 19 weeks. For each species, 50 animals of each sex were placed on test as controls for the group receiving the higher concentration and 49 to 50 animals were of each sex were placed on test as controls for the group receiving the lower concentration.
In both species, adequate numbers of animals in all groups survived long enough to be at risk from late-developing tumors.
Feeding of 5-nitro-o-anisidine to rats was associated with increased incidences of tumors of the integumentary system. Basal-cell carcinomas, trichoepitheliomas, squamous-cell carcinomas and sebaceous adenocarcinomas each occurred in the skin of high dose male rats at statistically significant incidences. For both male and female rats, carcinomas (the combined incidence of sebaceous adenocarcinomas, ceruminous carcinomas and squamous-cell carcinomas) of the Zymbal's gland or the skin of the ear were significant in the high dose groups. In the clitoral gland of dosed female rats, the incidence of carcinomas and the incidence of adenomas were each significant.
Among mice, the incidence of hepatocellular carcinoma was statistically significant for dose B females when compared to their appropriate controls.
Under the conditions of this bioassay, dietary administration of 5-nitro-o-anisidine was carcinogenic in Fischer 344 rats, causing tumors of the integumentary system in males and females and of the clitoral gland in females. The compound was also carcinogenic to female B6C3F1 mice, causing hepatocellular carcinomas.
Synonyms: 2-methoxy-5-nitro-benzeneamine; 3-amino-4-methoxy-nitrobenzene; 2-methoxy-5-nitroaniline; 2-amino-4-nitroanisole; Fast Scarlet R; C.I. Azoic Diazo Component 13
Report Date: 1978