Benzidine Dihydrochloride: Risk Assessment

Benzidine Dihydrochloride: Risk Assessment. LITTLEFIELD, N.A., NELSON, C. J., AND GAYLOR, D. W. (1984). Fundam. Appl. Toxicol.4, 69–80. Benzidine, recognized as a bladder carcinogenin man and as a liver carcinogen in experimental animals, isthe chemical basis of as many as 200 commercial dyes. Physiologicalprocesses can metabolize these dyes to release benzidine, therebycreating a potential exposure hazard. To assess this hazard,both sexes of F₁ hybrid (genetically homogeneous) and monohybrid(genetically heterogeneous) mice from a BALB/c male and C57BL/6female cross were exposed for their respective lifespans tobenzidine dihydrochloride in their drinking water at concentrationsof 0, 30, 40, 60, 80, 120, and 160 ppm for males, and 0, 20,30, 40, 60, 80, and 120 ppm for females. Animals were removedfrom the study when they were dead or moribund. This study wasterminated after 33 months of exposure. Using the endpoint ofhepatocellular adenomas and carcinomas, the Armitage Doll multistagemodel was used to describe the tumor rates in the experimentaldose range and to obtain the upper confidence level on tumorrates. Linear interpolation was used between zero dose and theupper confidence level of the lowest experimental dosage forpredicting potential low dose tumor rates. Dose-response effectson body weight, survival, and liver neoplasms were noted inboth stocks. For each of the endpoints, the females were moresusceptible than males and the F₁ (homogeneous) stock was moresusceptible than the monohybrid cross (heterogeneous). The calculatedvirtually "safe" dose predicted to produce less than one permillion F₁ female mice with a liver tumor is 0.045 ppb. Onepart per billion of benzidine dihydrochloride in the drinkingwater of these mice is estimated to produce liver tumors inless than 2.23 mice per 100,000 population.