Journal Article

Disposition of a Low Dose of Bisphenol A in Male and Female Cynomolgus Monkeys

Hideo Kurebayashi, Ryoko Harada, Richard K. Stewart, Hiroaki Numata and Yasuo Ohno

in Toxicological Sciences

Volume 68, issue 1, pages 32-42
Published in print July 2002 | ISSN: 1096-6080
Published online July 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/68.1.32
Disposition of a Low Dose of Bisphenol A in Male and Female Cynomolgus Monkeys

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Bisphenol A (BPA) is a weak estrogenic compound mass-produced with potential human exposure. Following a single oral or intravenous (iv) dose of 100 μg/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 Cmax = 104–107 ng-eq/ml between 0.25 and 2 h, and AUCoral = 244–265 ng-eq•h/ml after oral dosing. In the case of the iv dose, AUCiv 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 (t1/2iv = 13.5–14.7 h) than post-oral dose (t1/2oral = 9.63–9.80 h). After iv dose, the fast-phase half-life (t1/2f) of total radioactivity was 0.61–0.67 h. The t1/2f of unchanged14C-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 (fp = 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 (≤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.

Keywords: bisphenol A; monkeys; toxicokinetics; absorption; metabolism; excretion; glucuronide

Journal Article.  8056 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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