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
Clj. Li et Mo. James, 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, TOXICOL SCI, 57(1), 2000, pp. 75-86
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.