Benzidine dihydrochloride: toxicological assessment in mice during chronic exposures.

Although benzidine is recognized as a bladder carcinogen in humans and a liver carcinogen in laboratory animals, its toxicological effects appear to be extended to several other endpoints. This economically important chemical is the base for over 200 dyes and is used extensively in manufacturing. In a chronic lifespan study lasting 33 months, both sexes of F1 hybrid (genetically homogeneous) and monohybrid cross (genetically heterogeneous) mice from BALB/c male and C57BL/6 female crosses were exposed to benzidine dihydrochloride in their drinking water at concentrations of 0, 20, 30, 40, 60, 80, and 120 ppm for the females, and 0, 30, 40, 60, 80, 120, and 160 ppm for males. Animals were removed from the study when they were dead or moribund. In addition to hepatocellular carcinomas, there were several other toxicological end-points identified that appeared to be related to the administration of benzidine. Dose-response trends were noted for pigmentation of the spleen, hepatic cytological alterations, hyperplasia of the bile ducts, megakaryocytosis of the bone marrow, vacuolization of the brain, adenoma of the Harderian gland, atrophy of the ovaries, and angioma of the uterus. Also, dose-related effects were noted with respect to time to lung tumor and time to mortality due to reticulum-cell sarcomas.