Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

• Published in: Toxicology and applied pharmacology Vol. 267; no. 1; pp. 41 - 48
• Main Authors: Patterson, Tucker A., Twaddle, Nathan C., Roegge, Cindy S., Callicott, Ralph J., Fisher, Jeffrey W., Doerge, Daniel R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 15.02.2013; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Aglycones; AMNIOTIC FLUID; Animals; AUC; Benchmarks; Benzhydryl Compounds - pharmacokinetics; Bioindicators; Biological and medical sciences; biomonitoring; Bisphenol A; BLOOD; Cord blood; Data processing; Detoxification; Female; Fetal Blood - drug effects; Fetal Blood - metabolism; Fetus - drug effects; Fetus - metabolism; FETUSES; Food; Intravenous administration; INTRAVENOUS INJECTION; Macaca mulatta; MACACUS; Mass spectrometry; MASS SPECTROSCOPY; Maternal-Fetal Exchange - drug effects; Maternal-Fetal Exchange - physiology; Medical equipment; Medical sciences; METABOLISM; Monomers; Perinatal exposure; Pharmacokinetics; Phenols - pharmacokinetics; PLACENTA; Placental transfer; PLASTICS; polycarbonate; POLYCARBONATES; Pregnancy - blood; Pregnancy - drug effects; Pregnancy - metabolism; Primates; PYRAZOLINES; Rhesus monkey; Sampling; Toxicology; URINE; Bisphenol A; Rhesus monkey; Pharmacokinetics; Mass spectrometry; Placental transfer; Concurrent; Endocrine disruptor; Macaca mulatta; Assay; Vertebrata; Mammalia; Mother; Primates; Simioidea; Fetus; Quantitative analysis
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2012.12.006

Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (>90%) in amounts consistent with aggregate exposure at levels below 1μg/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100μg/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. ► Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ► Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ► BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ► BPA levels in monkey placenta are similar to other metabolically active tissues. ► Some published human cord blood data for BPA are inconsistent with these measurements.