Toxicological Sciences 68, 32-42 (2002)
Copyright © 2002 by the Society of Toxicology
BIOTRANSFORMATION AND TOXICOKINETICS |
Disposition of a Low Dose of Bisphenol A in Male and Female Cynomolgus Monkeys
* Division of Pharmacology, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya, Tokyo 158-8501, Japan; and
ITR Laboratories Canada Inc., 19601 Clark Graham, Montréal, Québec, Canada H9X 3T1
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.
Key Words: bisphenol A; monkeys; toxicokinetics; absorption; metabolism; excretion; glucuronide.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. G. Teeguarden, J. M. Waechter Jr., H. J. Clewell III, T. R. Covington, and H. A. Barton Evaluation of Oral and Intravenous Route Pharmacokinetics, Plasma Protein Binding, and Uterine Tissue Dose Metrics of Bisphenol A: A Physiologically Based Pharmacokinetic Approach Toxicol. Sci., June 1, 2005; 85(2): 823 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.'i. Yoshihara, T. Mizutare, M. Makishima, N. Suzuki, N. Fujimoto, K. Igarashi, and S. Ohta Potent Estrogenic Metabolites of Bisphenol A and Bisphenol B Formed by Rat Liver S9 Fraction: Their Structures and Estrogenic Potency Toxicol. Sci., March 1, 2004; 78(1): 50 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Domoradzki, C. M. Thornton, L. H. Pottenger, S. C. Hansen, T. L. Card, D. A. Markham, M. D. Dryzga, R. N. Shiotsuka, and J. M. Waechter Jr. Age and Dose Dependency of the Pharmacokinetics and Metabolism of Bisphenol A in Neonatal Sprague-Dawley Rats Following Oral Administration Toxicol. Sci., February 1, 2004; 77(2): 230 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kurebayashi, H. Betsui, and Y. Ohno Disposition of a Low Dose of 14C-Bisphenol A in Male Rats and Its Main Biliary Excretion as BPA Glucuronide Toxicol. Sci., May 1, 2003; 73(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|