The pharmacokinetics of [(3)H]-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 microg/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-beta-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.

1. Following a 0.25-mg/kg intrapericardial dose of the phenolic compound, 2-naphthol, to the American lobster, Homarus americanus, a two-compartment model best described the disposition of parent [14C]-2-naphthol in the haemolymph. Male and female lobsters had similar alpha-phase half lives of 26 +/- 19 min (mean +/- SD, n = 4) and 29 +/- 15 min respectively. The beta-phase half lives were significantly longer in males, 63.9 +/- 30.9 h, than in females, 30.6 +/- 6.8 h (p < 0.05). The total body clearance for females was 26.4 +/- 6.5 ml x h-1 x kg-1 and was higher than that of males, 11.1 +/- 5.9 ml x h-1 x kg-1 (p < 0.05). 2. 2-Naphthol was converted to 2-naphthyl-beta-D-glucoside (major metabolite) and 2-naphthyl sulphate (minor metabolite) such that at 24 h 39-60.6% of the radioactivity in haemolymph was 2-naphthyl-beta-D-glucoside, 38.6-58.9% 2-naphthol and 0.5-4% 2-naphthyl sulphate. 3. The 2-naphthol-derived radioactivity was > 99% bound to haemolymph proteins at 1 min and > 90% bound at 1 day after the dose, indicating that both 2-naphthol and 2-naphthyl-beta-D-glucoside were highly protein bound. 4. 2-Naphthyl-beta-D-glucoside was slowly eliminated from haemolymph in both males and females, with elimination half lives of 34-78 h. 2-Naphthyl-beta-D-glucoside was the major metabolite in urine samples collected at 5 days after the dose. Hepatopancreas and antennal gland contained glucosidase activities, and the long half life of 2-naphthyl-beta-D-glucoside could be explained by conjugation deconjugation cycling. 5. 2-Naphthyl sulphate was eliminated from haemolymph with a half-life < 10 h and was excreted in urine.