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

Journal Article · Thu Jun 15 04:00:00 EDT 2017 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2017.03.023· OSTI ID:22690987

Suh, M.; Proctor, D. M. ^[1]; Hays, S. M. ^[2]

---

1. ToxStrategies, Mission Viejo, CA (United States)
2. Summit Toxicology, PO Box 3209, Bozeman, MT 59715 (United States)

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. - Highlights: • 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.

• OSTI ID: 22690987
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 325; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGE GROUPS
BIOASSAY
CHROMIUM
DOSIMETRY
DRINKING WATER
GASTROINTESTINAL TRACT
HEALTH HAZARDS
MICE
NEOPLASMS
PH VALUE
PUBLIC HEALTH
RATS
RISK ASSESSMENT