METABOLISM AND DISPOSITION OF BENZIDINE IN THE DOG

The dog is an animal model for assessing aromatic amine-induced bladder cancer. For this reason, metabolism and disposition of benzidine in dog was assessed. Dogs were administered a 1 mg/kg i.v. dose of [3H]benzidine (16.4 mCi/mmol). The plasma t2-Jan of the radiolabeled material (benzidine plus metabolites) was significantly longer (∼3 h) than authentic benzidine (<30 min). During the 5 h experiment, the majority of radiolabel was associated with bile, urine and carcass. Bladder transitional epithelium exhibited a consistently higher concentration of bound radioactivity than bladder muscle. A significant amount of binding was observed in DNA from liver, kidney and bladder. DNA from bladder transitional epithelium exhibited the highest concentration of radioactivity. Approximately 30% of the radioactivity recovered following HPLC of urine or bile was identified as umnetabolized benzidine. 3-Hydroxy-benzidine was a major metabolite identified in bile (8%) but not urine. Urine samples treated with acid, base or sulfatase yielded 3-hydroxybenzidine (6%) as a major hydrolysis product. Similar treatment of bile samples did not result in increased amounts of 3-hydroxybenzidine. Neither N-acetylated nor N-methylated metabolites of benzidine were observed in urine or bile. Thus, considerable metabolism of benzidine occurs in dog by pathways that are yet to be determined. © 1990 Oxford University Press.