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

• Published in: Toxicology and applied pharmacology 2017-06, Vol.325, p.9-17
• Main Authors: Kirman, C.R., Suh, M., Proctor, D.M., Hays, S.M.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Administration, Oral; Adolescent; Adult; Age Factors; AGE GROUPS; Aged; Animals; BIOASSAY; Child; Child, Preschool; CHROMIUM; Chromium - administration & dosage; Chromium - pharmacokinetics; Chromium - toxicity; Circadian Rhythm; DOSIMETRY; Drinking; DRINKING WATER; Gastrointestinal Absorption; Gastrointestinal reduction; GASTROINTESTINAL TRACT; Gastrointestinal Tract - metabolism; HEALTH HAZARDS; Human variation; Humans; Hydrogen-Ion Concentration; Infant; Infant, Newborn; MICE; Middle Aged; Models, Biological; NEOPLASMS; Nonlinear Dynamics; PH VALUE; Physiologically based model; PUBLIC HEALTH; RATS; RISK ASSESSMENT; Species Specificity; Toxicokinetics; Water Pollutants - administration & dosage; Water Pollutants - pharmacokinetics; Water Pollutants - toxicity; Young Adult
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2017.03.023

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. •An 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.