Following the intraportal infusion of [3H]benzo[a]pyrene (BP) at two dose levels (5 and 0.125 mumol/kg) in the rat, metabolites were excreted via the bile and were released into the hepatic venous blood. At each dose level, a significant portion (approx. 15-18%) of biliary metabolites was directly extractable with ethyl acetate and a total of approx. 24-32% became extractable after incubation of bile with beta-glucuronidase. More than 65% and 70% of the 3H in blood and liver, respectively, was directly extractable with ethyl acetate. The h.p.l.c. profile of extracted metabolites was found to differ at the two dose levels studied. The binding of reactive metabolites to hepatic protein and DNa was measured at four dose levels of [3H]BP. The possible availability of hepatic-derived metabolites to extra-hepatic sites is discussed.
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Chipman et al. (1981) studied this question.