ToxSci Advance Access originally published online on August 12, 2003
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Toxicological Sciences 76, 21-34 (2003)
Copyright © 2003 by the Society of Toxicology
BIOTRANSFORMATION AND TOXICOKINETICS |
Metabolism and Pharmacokinetics of Bisphenol A (BPA) and the Embryo-Fetal Distribution of BPA and BPA-Monoglucuronide in CD Sprague-Dawley Rats at Three Gestational Stages
* Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674;
Dow Europe, GmbH, Horgen, Switzerland CH-8810; and
Bayer CropScience LP, Stillwell, Kansas 66085
The pharmacokinetics of bisphenol A (BPA), including the quantification of the major BPA metabolite BPA-monoglucuronide conjugate (BPA-glucuronide) was studied in Sprague-Dawley rats at different stages of gestation. 14C-BPA was administered orally at 10 mg BPA/kg body weight (0.2 mCi/rat) to nongravid rats and to other groups on gestation days (GD) 6, 14, and 17. GD 0 was when the vaginal smear was sperm positive or a copulatory plug was observed. Radioactivity derived from 14C-BPA was quantified in the maternal blood, selected tissues, and the embryo or fetus. BPA and BPA-glucuronide were quantified in maternal plasma and excreta. Additional rats were dosed orally at 10 mg 14C-BPA/kg (0.2 mCi/rat or 0.5 mCi/rat) on GD 11, 13, and 16 to further study the distribution of BPA and BPA-glucuronide to the embryo/fetal tissue. The tissue distribution, metabolism, or the rates or routes of excretion of BPA, or the plasma concentration-time profiles of BPA-glucuronide did not appear to be altered at any stage of gestation as compared to nonpregnant rats. In the GD 11 group, neither BPA nor BPA-glucuronide was detected in the yolk sacs or embryos, except for trace concentrations of BPA-glucuronide in the yolk sacs at 15 min postdosing. In the GD 13 group, both BPA and BPA-glucuronide were detected in the yolk sacs of the conceptus but not in the embryos/fetuses, except for BPA at 15 min. For the animals dosed with 0.2 mCi/rat on GD 16, both analytes were detected in the placentae at 15 min and 12 h, but not at 96 h. Traces of both analytes were detected in fetal tissue in two of five specimens at 15 min only. In rats dosed on GD 16 with 0.5 mCi/rat, the BPA-glucuronide and BPA concentrations in maternal plasma at 15 min were 1.7 and 0.06 µg equivalents (eq)/g plasma, respectively. At the same time postdosing in these animals, the placental BPA-glucuronide concentrations were lower (0.34 µg eq BPA [as glucuronide]/g), and the BPA concentrations were about equivalent (0.095 µg/g). Fetal BPA-glucuronide and BPA concentrations were markedly lower, 0.013 and 0.018 µg eq/g, respectively. Therefore, no selective affinity of either yolk sac/placenta or embryo/fetus for BPA or BPA metabolites relative to maternal plasma or tissues was observed in this study.
Key Words: bisphenol A; BPA-monoglucuronide metabolism, disposition; rats; pregnant; embryo; fetus.
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