Disposition and metabolic fate of benzo[a]pyrene in the brown bullhead

We have investigated the biological fate of intraperitoneally administered benzo[a]pyrene (BP) in brown bullhead (Ictalurus nebulosus) maintained in flowing water. The tissue distribution of benzo[a]pyrene‐derived radioactivity at 24 and 72 h after treatment was determined. The highest concentration of BP‐derived radioactivity was in bile (3.7 and 12.3 μg BP equivalents/g bile at 24 and 72 h, respectively). Biliary radioactivity amounted to 16% of the radioactivity found in the fish at 72 h. The major components of bile collected at 72 h were glucuronides (24%), water‐soluble conjugates unhydrolyzed by β‐glucuronidase or arylsulfatase (57%) and unmetabolized BP (10%). The potentially genotoxic metabolite BP‐7,8‐dihydrodiol and its glucuronide represented 3% of the radioactivity of the bile at 72 h. High concentrations of BP‐derived radioactivity were also present in liver and in kidney (920 and 290 ng equivalents of BP/g at 72 h, respectively). Although only low concentrations of BP‐derived radioactivity were detected in muscle (60 ng eq/g at 72 h), the proportion of the BP‐derived radioactivity found in this tissue at 72 h amounted to 16% of the radioactivity found in the fish. Unmetabolized BP represented 32% of the muscle radioactivity, and 96% of the radioactivity that could be extracted with ethyl acetate and characterized by HPLC. BP‐7,8‐dihydrodiol represented 0.2% of the muscle radioactivity. The amount of BP derivatives irreversibly bound to macromolecules and precipitable with trichloroacetic acid at 72 h amounted to 12 to 13% of the radioactivity present in each tissue. Furthermore, 21, 28 and 35% of the BP‐derived radioactivity could not be extracted with ethyl acetate from the insoluble components of muscle, kidney and liver, respectively, at 72 h. These data indicate that significant amounts of active metabolic intermediates of BP capable of alkylating DNA and other macromolecules were formed in bullhead tissues.