Benzidine mechanistic data and risk assessment: species- and organ-specific metabolic activation

The aromatic amine benzidine (BZ) has produced various tumors, including liver tumors, in mice, rats and hamsters. BZ forms DNA adducts in rodent liver, and it is positive in most genotoxicity tests. Only bladder tumors are produced in dogs and in humans who have been occupationally exposed, possibly related to the slow rate of liver detoxification by acetylation, allowing activation of BZ or its metabolites in urine. Despite these differences, risk assessment for humans, based on liver tumors in mice, was approximately predictive of the incidence of bladder tumors observed in industrially exposed humans.