Disposition of a low dose of bisphenol A in male and female cynomolgus monkeys

Bisphenol A (BPA) is a weak estrogenic compound mass-produced with potential human exposure. Following a single oral or intravenous (iv) dose of 100 mug/kg [ring-C-14(U)] radiolabeled bisphenol A (C-14-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 C-14-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 C-14-BPA for females (0.39 h) was smaller than that for males (0.57 h). These results suggested the distribution of lipophilic C-14-BPA in adipose tissue after iv dose, in contrast to first pass metabolism after oral dose. C-14-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 C-14-BPA and unchanged C-14-BPA was very low (less than or equal to51.5%) 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 C-14-BPA, were rapidly excreted into urine in monkeys.