Thirteen-week subchronic toxicity studies of Direct Blue 6, Direct Black 38, and Direct Brown 95 dyes

Abstract

Thirteen-week subchronic toxicity studies of Direct Blue 6, Direct Black 38, and Direct Brown 95 dyes were conducted by administering the test chemicals in feed to F344 rats and B6C3F1 mice. Groups of 10 rats and 10 mice of each sex were administered one of the three dyes at one of five concentrations for 13 weeks. The concentrations used for the rats ranged from 190 to 3000 ppm and those for the mice from 375 to 12,500 ppm. Matched controls were untreated. Deaths occurred among rats but not among mice during the test period. Benzidine and monoacetyl benzidine were detected in the urine of male and female rats and mice administered the test dyes, although no free benzidine was found in the dyes themselves (detection limit, 0.004%). In rats, neoplastic lesions of the liver, hepatocellular carcinomas, and neoplastic nodules, occurred only in the treated groups. The combined incidences were statistically significant for male rats given 1500 ppm Direct Blue 6 dye, for females administered 3000 ppm Direct Blue 6 dye, for males and females given 1500 ppm Direct Black 38 dye, and for females given 1500 ppm Direct Brown 95 dye. Male rats given Direct Brown 95 dye developed neither hepatocellular carcinomas nor neoplastic nodules, but had significant incidences of preneoplastic hepatic lesions. Males in groups given the largest dose died early from toxicity. In mice, no neoplastic lesions occurred in the liver or other tissues of groups administered the different dyes.