Maternal-fetal disposition of bisphenol a in pregnant Sprague-Dawley rats

This study describes the maternal-fetal disposition of bisphenol A and its distribution into the placenta and amniotic fluid after iv injection (2 mg/kg) to pregnant Sprague-Dawley rats. Bisphenol A was distributed extensively to the placenta and fetus, with their respective AUC values 4.4- and 2.2-fold greater than AUC for the maternal serum. In contrast, the distribution of bisphenol A into the amniotic fluid was low, with the mean amniotic fluid-to-maternal serum AUC ratio of 0.2. The decay curves of bisphenol A in the placenta, fetus, and amniotic fluid paralleled that of the maternal serum during the terminal elimination phase. A five-compartment open model consisting of the maternal central, maternal peripheral, placental, fetal, and amniotic fluid compartments was used to describe the disposition of bisphenol A in pregnant rats, with the elimination occurring from the maternal central and fetal compartments. Based on this model, bisphenol A delivered to the placenta was transferred primarily to the fetus [kpf/(kpf + kpc + kpa) = 65.4 %], with the remaining fraction transported to the maternal central (33.2%) and amniotic fluid (1.4%) compartments. Bisphenol A was eliminated from the amniotic fluid by the fetal (63.9%) and placental (36.1%) routes. On the other hand, bisphenol A was eliminated from the fetus primarily by the placental route back to mother [kfp/(kfp + kfa + kfo) = 100%], with the amniotic route playing an insignificant role in fetal elimination. The percent contribution of the fetal elimination to the total elimination in the maternal-fetal unit was 0.0% [CLfoAUCfetus/(CLcoAUCmaternal serum + CLfoAUCfetus)]. The pharmacokinetic model used in this study provides insights into the routes of elimination of bisphenol A in the maternal-fetal rat upon maternal administration.