Abstract for TR-225

A carcinogenesis bioassay of D & C Red No. 9, a pigment used in topical drugs and cosmetics, was conducted by feeding diets containing 1,000 or 3,000 ppm of the test substance (89.8% pure) to groups of 50 F344 rats of either sex for 103 weeks. Similar groups of 50 B6C3F1 mice received diets containing 1,000 or 2,000 ppm of the test substance for 103 weeks. Groups of 50 untreated rats and mice of either sex served as controls.

In a 13-week subchronic study, the spleens of most dosed rats were enlarged and pigment (unidentified) was present in the renal tubular epithelium. Lymphoreticular hyperplasia of thymic lymph nodes was found in 75-100% of females receiving 6,000-50,000 ppm D & C Red No. 9 and in 70-100% of male rats receiving 3,000-25,000 ppm. Hemosiderosis of the liver was observed at the high-dose levels in male and female rats. Mice receiving 1,250 ppm or more D & C Red No. 9 had congestion of the spleen and hemosiderin deposits. Thus, the selection of doses for the chronic study was based on the appearance of hemosiderosis and the incidences and severity of splenic lesions observed in the 91-day subchronic study.

In the chronic study, mean body weights of dosed rats of either sex and of male mice were comparable with those of controls. After week 50, the mean body weight of high-dose female mice was lower than that of the controls. No compound-related effects on survival or clinical signs were observed for rats or mice of either sex. With the possible exception of female mice, all other dosed groups of rats or mice might have tolerated higher doses, thus a clear maximum tolerated dose may not have been utilized in this study.

Splenic sarcomas (0/50, 0/50, 26/48; P<0.001) and neoplastic nodules of the liver (0/50, 6/50, 7/49; P<0.01) were observed in high-dose male rats at incidences significantly higher than those in the controls. Incidences of neoplastic nodules in the livers (1/50, 1/50, 5/50) of female rats showed a statistically significant (P<0.05) trend. Nonneoplastic splenic lesions were also observed in dosed male and female rats.

Lymphocytic leukemia was observed in dosed male (10/50, 2/50, 2/50) and female (10/50, 2/50, 1/50) rats at statistically significant (P<0.05) decreased incidences, compared with controls. Adenomas or carcinomas of the preputial gland in male rats (7/50, 2/50, 0/50) occurred with a statistically significant (P<0.01) negative relationship to dose of D & C Red No. 9 (P=0.007).

Under the conditions of this bioassay, D & C Red No. 9 was carcinogenic for male F344 rats causing an increased incidence of sarcomas of the spleen and a dose-related increase in neoplastic nodules of the liver. D & C Red No. 9 was not considered to be carcinogenic to female F344 rats, although the increased incidence of neoplastic nodules of the liver may have been associated with administration of the test chemical. D & C Red No. 9 was not carcinogenic for B6C3F1 mice of either sex.