Journal Article

Oral Bioavailability and Pharmacokinetics of Elimination of 9-Hydroxybenzo[a]pyrene and Its Glucoside and Sulfate Conjugates after Administration to Male and Female American Lobsters, <i>Homarus americanus</i>

C.-L. J. Li and M. O. James

in Toxicological Sciences

Volume 57, issue 1, pages 75-86
Published in print September 2000 | ISSN: 1096-6080
Published online September 2000 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/57.1.75
Oral 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

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The pharmacokinetics of [3H]-9-hydroxybenzo[a]pyrene (9-OH-BaP), a highly lipophilic primary metabolite of benzo(a)pyrene, were examined after intrapericardial (iv) or oral doses of 50 or 200 μg/kg to intermolt American lobsters, Homarus americanus. Combining data for all lobsters, the average terminal 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 benzo(a)pyrene (720 h). The oral bioavailability of parent 9-OH-BaP, calculated from the area under the hemolymph concentration curve, was 15.9%. The low bioavailability and variable elimination rates were attributed to extensive first-pass conjugation and sequestration in the hepatopancreas. BaP-9-sulfate 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-β-D-glucoside was a minor metabolite in most hemolymph and tissue samples; an exception was hemolymph from the iv high-dose group. Concentrations of 9-OH-BaP and metabolites in the edible muscle tissue were similar to those in hemolymph, and 9-OH-BaP residues at 10 to 16 days after the dose were 3 to 12 ng/g muscle. Sulfotransferase and UDP-glucosyltransferase (UGT) activities with 9-OH-BaP were found in the antennal gland, intestinal mucosa, and hepatopancreas (UGT only). Sulfatase activity with BaP-9-sulfate, found in both the hepatopancreas and the antennal gland, was thought to contribute to metabolite cycling. These studies showed that 9-OH-BaP was readily conjugated to sulfate and glucose in the lobster, and that despite their high lipophilicity, 9-OH-BaP and conjugates were excreted from the lobster hemolymph and tissues much more rapidly than benzo[a]pyrene.

Keywords: 9-hydroxybenzo(a)pyrene; lobster; bioavailability; sulfation of 9-hydroxybenzo(a)pyrene; glucose conjugation; accumulation of lipophilic xenobiotic

Journal Article.  8939 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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