Prediction of human prenatal exposure to bisphenol A and bisphenol A glucuronide from an ovine semi-physiological toxicokinetic model - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2017

Prediction of human prenatal exposure to bisphenol A and bisphenol A glucuronide from an ovine semi-physiological toxicokinetic model

Glenn Gauderat
  • Fonction : Auteur
Pierre-Louis Toutain
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  • PersonId : 1204213
Rémi Servien
Sylvie Puel
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  • PersonId : 1019569
Marlène Z. Lacroix
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Tanguy Corbel
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Alain Bousquet‐mélou
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  • PersonId : 1207361

Résumé

Bisphenol A (BPA) risk assessment is hampered by the difficulty of determining the extent of internal exposure in the human fetus and uncertainties regarding BPA toxicokinetics (TK) in the maternal-fetal unit. A feto-maternal TK model describing BPA and BPA glucuronide (BPAG) disposition in sheep was humanized, using human TK data obtained after d6-BPA administration on a cookie, to predict BPA and BPAG kinetics in the human mother-fetus unit. Validation of the model predictions included the assessed dose proportionality of BPA and BPAG disposition and the similarity between the simulated and measured time courses of BPA and BPAG in fetal rhesus monkeys after BPA maternal dosing. The model predicted fluctuations in fetal BPA concentrations associated with typical maternal exposure to BPA through the diet, with similar trough (0.011 ng/L vs 0.014 ng/L) and lower peak BPA concentrations (0.023 ng/L vs 0.14 ng/L) in fetal than in maternal plasma. BPAG concentrations in fetal plasma were predicted to increase over time to reach a steady value (29 ng/L) reflecting the cumulative BPA dose received by the fetus. Model-predicted BPAG concentrations in fetal plasma are consistent with reported levels in human cord blood that may be considered as relevant markers of the BPA dose entering blood throughout fetal life.
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Dates et versions

hal-02628446 , version 1 (26-05-2020)

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Glenn Gauderat, Nicole Picard-Hagen, Pierre-Louis Toutain, Rémi Servien, Catherine Viguié, et al.. Prediction of human prenatal exposure to bisphenol A and bisphenol A glucuronide from an ovine semi-physiological toxicokinetic model. Scientific Reports, 2017, 7 (1), ⟨10.1038/s41598-017-15646-5⟩. ⟨hal-02628446⟩
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