Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A Public Deposited

http://ir.library.oregonstate.edu/concern/articles/7d278v70g

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at:  http://www.journals.elsevier.com/toxicology-and-applied-pharmacology/

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  • A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d₆-BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d₆-BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult human model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d₆-BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species.
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  • Yang, X., Doerge, D. R., Teeguarden, J. G., & Fisher, J. W. (2015). Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A. Toxicology and Applied Pharmacology, 289(3), 442-456. doi:10.1016/j.taap.2015.10.016
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  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2016-01-11T16:15:38Z No. of bitstreams: 1 TeeguardenJustinEnvironMolecularToxDevelopmentPhysiologicallyBased.pdf: 1707519 bytes, checksum: f6ff37e080ee52e7b4048a712f61105b (MD5)
  • description.provenance : Made available in DSpace on 2016-01-11T16:15:54Z (GMT). No. of bitstreams: 1 TeeguardenJustinEnvironMolecularToxDevelopmentPhysiologicallyBased.pdf: 1707519 bytes, checksum: f6ff37e080ee52e7b4048a712f61105b (MD5) Previous issue date: 2015-12-15
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2016-01-11T16:15:54Z (GMT) No. of bitstreams: 1 TeeguardenJustinEnvironMolecularToxDevelopmentPhysiologicallyBased.pdf: 1707519 bytes, checksum: f6ff37e080ee52e7b4048a712f61105b (MD5)

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