An integrated exposure and pharmacokinetic modeling framework for assessing population-scale risks of phthalates and their substitutes

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dc.contributor.authorWu, Yaoxingen
dc.contributor.authorSong, Zidongen
dc.contributor.authorLittle, John C.en
dc.contributor.authorZhong, Minen
dc.contributor.authorLi, Hongwanen
dc.contributor.authorXu, Yingen
dc.date.accessioned2022-03-22T11:56:26Zen
dc.date.available2022-03-22T11:56:26Zen
dc.date.issued2021-11en
dc.description.abstractTo effectively incorporate in vitro-in silico-based methods into the regulation of consumer product safety, a quantitative connection between product phthalate concentrations and in vitro bioactivity data must be established for the general population. We developed, evaluated, and demonstrated a modeling framework that integrates exposure and pharmacokinetic models to convert product phthalate concentrations into population-scale risks for phthalates and their substitutes. A probabilistic exposure model was developed to generate the distribution of multi-route exposures based on product phthalate concentrations, chemical properties, and human activities. Pharmacokinetic models were developed to simulate population toxicokinetics using Bayesian analysis via the Markov chain Monte Carlo method. Both exposure and pharmacokinetic models demonstrated good predictive capability when compared with worldwide studies. The distributions of exposures and pharmacokinetics were integrated to predict the population distributions of internal dosimetry. The predicted distributions showed reasonable agreement with the U.S. biomonitoring surveys of urinary metabolites. The "source-tooutcome" local sensitivity analysis revealed that food contact materials had the greatest impact on body burden for di(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di(isononyl) cyclohexane-1,2dicarboxylate (DINCH), and di(2-propylheptyl) phthalate (DPHP), whereas the body burden of diethyl phthalate (DEP) was most sensitive to the concentration in personal care products. The upper bounds of predicted plasma concentrations showed no overlap with ToxCast in vitro bioactivity values. Compared with the in vitro-toin vivo extrapolation (IVIVE) approach, the integrated modeling framework has significant advantages in mapping product phthalate concentrations to multi-route risks, and thus is of great significance for regulatory use with a relatively low input requirement. Further integration with new approach methodologies will facilitate these in vitro-in silico-based risk assessments for a broad range of products containing an equally broad range of chemicals.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.envint.2021.106748en
dc.identifier.eissn1873-6750en
dc.identifier.issn0160-4120en
dc.identifier.other106748en
dc.identifier.pmid34256300en
dc.identifier.urihttp://hdl.handle.net/10919/109383en
dc.identifier.volume156en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectSVOCsen
dc.subjectPhthalatesen
dc.subjectExposure modelingen
dc.subjectRisk assessmenten
dc.subjectPharmacokinetic (PK) modelingen
dc.subjectPhysiologically based pharmacokinetic (PBPK) modelingen
dc.titleAn integrated exposure and pharmacokinetic modeling framework for assessing population-scale risks of phthalates and their substitutesen
dc.title.serialEnvironment Internationalen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Civil and Environmental Engineering
Destination Area: Global Systems Science (GSS)