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Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations

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ABSTRACT A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding… Click to show full abstract

ABSTRACT A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH‐dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non‐linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. HIGHLIGHTSAn improved version of the PBPK model for Cr(VI) toxicokinetics was developed.The model incorporates data collected to fill important data gaps.Model predictions for specific age groups and sensitive subpopulations are provided.Implications to human health risk assessment are discussed.

Keywords: rats humans; based pharmacokinetic; mice rats; physiologically based; model; chromium mice

Journal Title: Toxicology and Applied Pharmacology
Year Published: 2017

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