Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

Abstract

We investigated the metabolic fate of a low dose (25 micro g/kg) of bisphenol A [2,2-bis(4-hydroxy-phenyl)propane] (BPA) injected subcutaneously in CD1 pregnant mice using a tritium-labeled molecule. Analytic methods were developed to allow a radio-chromatographic profiling of BPA residues in excreta and tissues, as well as in mothers' reproductive tracts and fetuses, that contained more than 4% of the administered radioactivity. BPA was extensively metabolized by CD1 mice. Identified metabolite structures included the glucuronic acid conjugate of BPA, several double conjugates, and conjugated methoxylated compounds, demonstrating the formation of potentially reactive intermediates. Fetal radioactivity was associated with unchanged BPA, BPA glucuronide, and a disaccharide conjugate. The latter structure, as well as that of a dehydrated glucuronide conjugate of BPA (a major metabolite isolated from the digestive tract), showed that BPA metabolic routes were far more complex than previously thought. The estrogenicity of the metabolites that were identified but not tested for hormonal activity cannot be ruled out; however, in general, conjugated BPA metabolites have significantly lower potency than that of the parent compound. Thus, these data suggest the parental compound is responsible for the estrogenic effects observed in fetuses exposed to BPA during gestation in this mammalian model.

Cited by papers we hold 8

• Bisphenol A and Hormone-Associated Cancers · 2015
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• Dose-Dependent Incidence of Hepatic Tumors in Adult Mice following Perinatal Exposure to Bisphenol A · 2014
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• Effects of Low Doses of Bisphenol A on the Metabolome of Perinatally Exposed CD-1 Mice · 2013
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• Perinatally Administered Bisphenol A as a Potential Mammary Gland Carcinogen in Rats · 2013
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• Perinatal Exposure to Environmentally Relevant Levels of Bisphenol A Decreases Fertility and Fecundity in CD-1 Mice · 2010
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• Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure · 2010
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• Prenatal Bisphenol A Exposure Induces Preneoplastic Lesions in the Mammary Gland in Wistar Rats · 2006
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• The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function In Vivo and Induces Insulin Resistance · 2005
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