title: Disposition of a low dose of bisphenol a in male and female cynomolgus monkeys.
abstract: Bisphenol A (BPA) is a weak estrogenic compound mass-produced with potential human exposure. Following a single oral or intravenous (iv) dose of 100 microg/kg [ring-14C(U)] radiolabeled bisphenol A (14C-BPA) to male and female cynomolgus monkeys, 79-86% of the administered radioactivity was excreted in urine over 7 days, and most of the urinary excretion was recovered by 24 h after dosing, a large part of this occurring within 12 h. The fecal excretion of radioactivity over 7 days was minimal (1.8-3.1%). Toxicokinetic parameters obtained from plasma 14C-BPA-derived radioactivity during 48 h were C(max) = 104-107 ng-eq/ml between 0.25 and 2 h, and AUC(oral) = 244-265 ng-eq*h/ml after oral dosing. In the case of the iv dose, AUC(iv) was 377-382 ng-eq*h/ml, and the bioavailability was 0.66-0.70. The terminal elimination half-life was larger post-iv dose (t(1/2iv) = 13.5-14.7 h) than post-oral dose (t(1/2oral) = 9.63-9.80 h). After iv dose, the fast-phase half-life (t(1/2f)) of total radioactivity was 0.61-0.67 h. The t(1/2f) of unchanged 14C-BPA for females (0.39 h) was smaller than that for males (0.57 h). These results suggested the distribution of lipophilic 14C-BPA in adipose tissue after iv dose, in contrast to first pass metabolism after oral dose. 14C-BPA-derived radioactivity was strongly bound to plasma protein (f(p) = 0.055). Radio-HPLC analysis suggested the predominant plasma and urinary metabolites were mono- and diglucuronide of 14C-BPA and unchanged 14C-BPA was very low (< or =1.5%) after oral dose. These results indicate that the intestinal absorption and metabolism of BPA was rapid and extensive, and the major metabolites, glucuronide conjugates of 14C-BPA, were rapidly excreted into urine in monkeys.
authors.affiliation: Division of Pharmacology, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya, Tokyo 158-8501, Japan. kurebaya@nihs.go.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Kurebayashi
authors.forename: Ryoko
authors.initials: R
authors.lastname: Harada
authors.forename: Richard K
authors.initials: RK
authors.lastname: Stewart
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Numata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohno
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002250:Carbon Radioisotopes; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds