Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure via silastic capsules in pregnant rhesus monkeys: Relevance for human exposures

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 45; pp. 105 - 116
• Main Authors: vom Saal, Frederick S., VandeVoort, Catherine A., Taylor, Julia A., Welshons, Wade V., Toutain, Pierre-Louis, Hunt, Patricia A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2014; Elsevier
• Subjects: Administration, Oral; Animals; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - blood; Benzhydryl Compounds - chemistry; Benzhydryl Compounds - pharmacokinetics; Bisphenol A; Capsules; Dimethylpolysiloxanes - chemistry; Environmental Exposure; Estrogens, Non-Steroidal - administration & dosage; Estrogens, Non-Steroidal - blood; Estrogens, Non-Steroidal - chemistry; Estrogens, Non-Steroidal - pharmacokinetics; Female; Fetus; Humans; Life Sciences; Macaca mulatta; Maternal; Maternal-Fetal Exchange; Pharmacokinetics; Phenols - administration & dosage; Phenols - blood; Phenols - chemistry; Phenols - pharmacokinetics; Pregnancy; Pregnancy - blood; Pregnancy - metabolism; Rhesus monkey; Pregnancy; Bisphenol A; Maternal; Rhesus monkey; Fetus; Pharmacokinetics
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2014.01.007

•dBPA pharmacokinetics differed in non-pregnant and pregnant female monkeys.•Serum conjugated/unconjugated dBPA was higher feeding dBPA than with sc capsules.•Mothers with highest unconjugated serum dBPA had lowest conjugated/unconjugated ratio.•Capsules led to higher unconjugated and lower conjugated dBPA in mothers than fetuses.•Oral dBPA led to adverse effects in fetal lungs, brain, mammary glands and ovaries. We measured serum dBPA in non-pregnant and pregnant female rhesus monkeys, fetuses and amniotic fluid. dBPA was administered by a daily oral bolus or sc implantation of Silastic capsules; both resulted in daily average serum unconjugated dBPA concentrations of <1ng/ml. We observed lower serum concentrations of unconjugated dBPA in pregnant females relative to pre-pregnancy values, and generally lower concentrations in fetal serum than in maternal serum. Differences in pharmacokinetics of dBPA were evident between pre-pregnancy, early and late pregnancy, likely reflecting changes in maternal, fetal and placental physiology. The serum ratio of conjugated to unconjugated dBPA after continuous sc release of dBPA was similar to values reported in human biomonitoring studies and markedly lower than with oral administration, suggesting oral bolus exposure is not an appropriate human exposure model. We report elsewhere that there were numerous adverse effects on fetuses exposed to very low serum dBPA in these studies.