MATERNAL-FETAL DISPOSITION OF BISPHENOL A IN PREGNANT SPRAGUE-DAWLEY RATS

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 2002-03, Vol.65 (5-6), p.395-406
• Main Authors: Shin, Beom Soo, Yoo, Sun Dong, Cho, Chang Youn, Jung, Ji Hoon, Lee, Byung Mu, Kim, Jung Ha, Lee, Kang Choon, Han, Soon-Young, Kim, Hyung Sik, Park, Kui Lea
• Format: Article
• Language: English
• Subjects: Animals; Area Under Curve; Benzhydryl Compounds; Estrogens, Non-Steroidal - pharmacokinetics; Female; Kinetics; Maternal-Fetal Exchange; Phenols - pharmacokinetics; Placenta - chemistry; Placenta - physiology; Pregnancy; Rats; Rats, Sprague-Dawley; Tissue Distribution
• ISSN: 1528-7394; 1087-2620
• DOI: 10.1080/15287390252808064

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 [ k pf /( k pf + k pc + k pa ) = 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 [ k fp /( k fp + k fa + k fo ) = 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 0.05% [CL fo AUC fetus /(CL co AUC maternal serum + CL fo AUC fetus )]. 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.