Development of a physiologically-based pharmacokinetic model of 2-phenoxyethanol and its metabolite phenoxyacetic acid in rats and humans to address toxicokinetic uncertainty in risk assessment
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- 作者：John A. Troutmana ; troutman.ja@pg.com" class="auth_mail" title="E-mail the corresponding author ; David L. Rickb ; LRick@dow.com" class="auth_mail" title="E-mail the corresponding author ; Sharon B. Stuarda ; stuard.sb@pg.com" class="auth_mail" title="E-mail the corresponding author ; Jeffrey Fisherc ; jeffrey.fisher@fda.hhs.gov" class="auth_mail" title="E-mail the corresponding author ; Michael J. Bartelsb ; MJBartels@dow.com" class="auth_mail" title="E-mail the corresponding author
- 关键词：Dosimetry ; Ethylene glycol phenyl ether ; PBPK ; Pharmacokinetics ; Toxicokinetics ; Uncertainty factors
- 刊名：Regulatory Toxicology and Pharmacology
- 出版年：2015
- 出版时间：November 2015
- 年：2015
- 卷：73
- 期：2
- 页码：530-543
- 全文大小：1396 K
文摘
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PhE risk assessment is confounded by species and dose route differences in toxicity.
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A PBPK model is presented to address these confounding factors.
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Systemic AUC was selected as the appropriate dose metric for risk assessment.
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Aggregate human exposure via dermal and oral routes was compared to rat oral NOAELs.
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In all cases, the calculated MOEs are above the PBPK-refined total UF of 25.