Perinatal Exposure to Bisphenol A: The Route of Administration Makes the Dose

Abstract

PP-31-125 Background/Aims: Bisphenol A (BPA) is subject to wide controversy regarding its pharmacokinetic behavior, especially regarding peri- and postnatal exposure. Recent epidemiological findings regarding inhaled BPA revealed that male sexual dysfunction was observed even in low levels of overall daily intake (0.5 μg/kg bw). The objective of this work was to investigate the effect of (a) the actual exposure to BPA on the developing fetus during the perinatal period and to reduce the uncertainty regarding the affecting parameters (fetus sulfation and BPA_Glu deconjugation by β-glucuronidase in the placenta) and (b) administration route to BPA bioavailability. Methods: A dynamic lifetime mother-fetus PBTK model was developed for BPA, which was capable of deriving the BPA biologically effective dose through the various developmental stages and under different administration routes, integrating uncertainty through Markov chain Monte Carlo analysis under steady-state and dynamic conditions. Results: Our results show that the fetus biologically effective dose of BPA during gestation is highly linked to the level of BPA in the mother's blood due to its high lipophilicity and small molecular weight; still this dose is almost 5 times lower than that of the mother (0.005 μg/L under a typical EFSA exposure scenario for the mother, 0.001 μg/L for the fetus). Sensitivity analysis confirmed that the dominant parameter regulating fetus free plasma BPA is fetus sulfation capacity and, to a smaller degree, placental BPA-Glu deconjugation by β-glucuronidase. Conclusion: BPA bioavailability from inhalation exposure in adults is 6 times higher than when BPA is orally administrated because of lack of first pass metabolism before systemic circulation entrance. Exposure to 5 μg/m3 of BPA in the air corresponds to a steady-state plasma concentration of 0.22 μg/L. In neonates, the overall clearance capability of whom is limited to almost 20% of the adult, differences in BPA bioavailability due to administration route are limited to 50%.