title: Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.
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.
authors.affiliation: Summit Toxicology, PO Box 3209, Bozeman, MT 59715, United States. Electronic address: ckirman@summittoxicology.com.
authors.forename: C R
authors.initials: CR
authors.lastname: Kirman
authors.affiliation: ToxStrategies, Mission Viejo, CA, United States.
authors.forename: M
authors.initials: M
authors.lastname: Suh
authors.affiliation: ToxStrategies, Mission Viejo, CA, United States.
authors.forename: D M
authors.initials: DM
authors.lastname: Proctor
authors.affiliation: Summit Toxicology, PO Box 3209, Bozeman, MT 59715, United States.
authors.forename: S M
authors.initials: SM
authors.lastname: Hays
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002857:Chromium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002940:Circadian Rhythm; D004326:Drinking; D065569:Gastrointestinal Absorption; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D051381:Rats; D018570:Risk Assessment; D013045:Species Specificity; D014873:Water Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D055815:Young Adult
chemical_list: D014873:Water Pollutants; D002857:Chromium; C074702:chromium hexavalent ion
keywords: Chromium; Gastrointestinal reduction; Human variation; Physiologically based model; Toxicokinetics