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

Abstract

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 1 μg/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 (100 μg/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. Thismore » 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. - Highlights: ► 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.« less

Authors:
 [1];  [2];  [1];  [3];  [2];  [2]
  1. Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)
  2. Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)
  3. U.S. Food and Drug Administration and Priority One Services Corp, Jefferson, AR 72079 (United States)
Publication Date:
OSTI Identifier:
22285238
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 267; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMNIOTIC FLUID; AUC; BLOOD; FETUSES; INTRAVENOUS INJECTION; MACACUS; MASS SPECTROSCOPY; METABOLISM; PLACENTA; PLASTICS; POLYCARBONATES; PYRAZOLINES; URINE

Citation Formats

Patterson, Tucker A., Twaddle, Nathan C., Roegge, Cindy S., Callicott, Ralph J., Fisher, Jeffrey W., and Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2012.12.006.
Patterson, Tucker A., Twaddle, Nathan C., Roegge, Cindy S., Callicott, Ralph J., Fisher, Jeffrey W., & Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys. United States. doi:10.1016/J.TAAP.2012.12.006.
Patterson, Tucker A., Twaddle, Nathan C., Roegge, Cindy S., Callicott, Ralph J., Fisher, Jeffrey W., and Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov. Fri . "Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys". United States. doi:10.1016/J.TAAP.2012.12.006.
@article{osti_22285238,
title = {Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys},
author = {Patterson, Tucker A. and Twaddle, Nathan C. and Roegge, Cindy S. and Callicott, Ralph J. and Fisher, Jeffrey W. and Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov},
abstractNote = {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 1 μg/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 (100 μg/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. - Highlights: ► 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.},
doi = {10.1016/J.TAAP.2012.12.006},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 267,
place = {United States},
year = {Fri Feb 15 00:00:00 EST 2013},
month = {Fri Feb 15 00:00:00 EST 2013}
}