Oval bioavailability and pharmacokinetics of elimination of 9-hydroxybenzo[a]pyrene and its glucoside and sulfate conjugates after administration to male and female American lobsters, Homarus americanus

The pharmacokinetics of [H-3]-9-hydroxybenzo[a]pyrene (9-OH-BaP), a highly lipophilic primary metabolite of benzo(a)pyrene, were examined after intrap ericardial (iv) or oral doses of 50 or 200 mug/kg to intermolt American lob sters, Homarus americanus, Combining data for all lobsters, the average ter minal elimination half-life of parent 9-OH-BaP was 97.3 h after iv and 56.5 h after oral administration, considerably less than found previously for b enzo(a)pyrene (720 h), The oral bioavailability of parent 9-OH-BaP, calcula ted from the area under the hemolymph concentration curve, was 15.9%. The l ow bioavailability and variable elimination rates were attributed to extens ive first-pass conjugation and sequestration in the hepatopancreas. BaP-9-s ulfate was the major metabolite. Hemolymph concentrations of BaP-9-sulfate increased up to one day after the dose, and then decreased, with a terminal elimination half-life of 45 h. BaP 9-beta -D-glucoside was a minor metabol ite in most hemolymph and tissue samples; an exception was hemolymph from t he iv high-dose group. Concentrations of 9-OH-BaP and metabolites in the ed ible muscle tissue mere similar to those in hemolymph, and 9-OH-BaP residue s at 10 to 16 days after the dose were 3 to 12 ng/g muscle. Sulfotransferas e and UDP-glucosyltransferase (UGT) activities with 9-OH-BaP were found in the antennal gland, intestinal mucosa, and hepatopancreas (UGT only). Sulfa tase activity with BaP-9-sulfate, found in both the hepatopancreas and the antennal gland, was thought to contribute to metabolite cycling. These stud ies showed that 9-OH-BaP was readily conjugated to sulfate and glucose in t he lobster, and that despite their high lipophilicity, 9-OH-BaP and conjuga tes were excreted from the lobster hemolymph and tissues much more rapidly than benzo[a]pyrene.