Toxicokinetics of bisphenol A in pregnant DA/Han rats after single i.v. application.
Bisphenol A (BPA) is an important chemical in the production of epoxy resins and polycarbonate plastics, and basic monomers which are used for a variety of applications. Consumer exposure to BPA may be possible from migration of BPA from dental sealants or from polycarbonate or epoxy-lined food and drink containers. BPA is known to act as weak estrogen mimic in rodents, and there is a concern of adverse endocrine effects, especially from prenatal exposure to this potential 'endocrine disruptor'. To address this concern, we have studied the disposition and transplacental transfer of BPA in pregnant DA/Han rats on day 18 of gestation. The BPA concentrations were determined by GC/MS analysis in maternal blood, maternal organs (liver, kidney, uterus), placenta and fetuses (fetal liver and residual tissues) at different time-points (5-360 min) after intravenous administration of 10 mg BPA/kg body weight. Total BPA (aglycone and conjugates) was analyzed in all tissue samples after enzymatic hydrolysis and liquid/liquid extraction; in maternal plasma, total BPA and BPA aglycone were analyzed in parallel samples (with/without hydrolysis). Soon (5 min) after the i.v. injection a mean total BPA concentration of 3.8 microg/ml was found in maternal plasma; it declined in the first 2 h to 0.7 microg/ml. Early after injection, the majority of circulating BPA (almost 80%) was still in the aglycone form, but, metabolism by phase II enzymes decreased the BPA aglycone concentration to 0.3 microg/ml after 2 h. Despite this efficient conjugation, BPA was rapidly distributed in the organism: In well perfused organs peak concentrations for total BPA were attained 20-30 min after intravenous administration, with mean values of about 9.7 microg/g in maternal liver, 8.6 microg/g in kidneys, and 6.2 microg/g in the uterus. The peak values in other tissues were lower, with 4.0 microg/g for placenta, 3.3 microg/g for fetal liver, and 2.4 microg/g for residual fetus homogenate. The BPA levels in all tissues thereafter declined more or less in parallel with those in maternal blood. The rather similar concentration time course in placenta and fetal liver indicates that BPA is readily transferred across the placenta of DA/Han rats to the fetus. Our data on BPA disposition in DA/Han rats are discussed in the context of other kinetic studies with BPA in pregnant rats, and in relation to the previous results from our laboratory (Degen et al. Arch Toxicol 76:23-29, 2002a, b, c) demonstrating comparable transplacental transfer of daidzein, a phytoestrogen that accounts for a significant portion of total human exposure to potential endocrine disruptors.
Moors
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Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Diel
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Degen
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D000818:Animals; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005865:Gestational Age; D007275:Injections, Intravenous; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors; D014018:Tissue Distribution; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds