Bioassay of 1,5-naphthalenediamine for possible carcinogenicity.

A bioassay of 1,5-naphthalenediamine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 1,5-Naphthalenediamine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The high and low dietary concentrations utilized in the chronic bioassay were, respectively, 0.1 and 0.05 percent for rats and 0.2 and 0.1 percent for mice. The compound was administered in the diet for 103 weeks, followed by up to 4 weeks of observation. Fifty mice of each sex and 25 rats of each sex were placed on test as controls. These animals were observed for up to 110 weeks. There were no significant positive associations between the administered concentrations of 1,5-naphthalenediamine and mortality in either sex of rats or mice. In all groups adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. Among dosed female rats, a statistically significant increase in endometrial stromal polyps was observed. Several of these tumors underwent malignant transformation to endometrial stromal sarcomas. The incidence of female rats having either adenoma or carcinoma of the clitoral gland was statistically significant. No neoplasms were observed at significantly increased incidences in dosed male rats. Based on lack of clinical signs or weight loss, the male rats may have been able to withstand a higher dose. In mice, dose-related increases in thyroid neoplasms were observed in both sexes. The incidence of thyroid C-cell carcinomas was significant for high dose female mice. The combined incidences of papillary adenomas, follicular-cell adenomas and papillary cystadenomas of the thyroid were significant for mice of both sexes. The incidence of hepatocellular carcinomas and the incidence of alveolar/bronchiolar adenomas were each significant for dosed female mice. Under the conditions of this bioassay, 1,5-naphthalenediamine was carcinogenic in female Fischer 344 rats, causing clitoral and uterine neoplasms. 1,5-Naphthalenediamine was also carcinogenic for B6C3F1 mice, producing thyroid neoplasms in males and neoplasms of the thyroid, liver, and lung in females. Insufficient evidence was provided for the carcinogenicity of the compound in male Fischer 344 rats.