A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices

Journal Article · Wed Oct 15 04:00:00 EDT 2014 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2014.08.010· OSTI ID:22439882

Sasso, Alan F.

Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.

• OSTI ID: 22439882
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 280; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BINDING ENERGY
CHEMISTRY
CHROMIUM
CONCENTRATION RATIO
DRINKING WATER
FORECASTING
HUMAN POPULATIONS
MICE
NEOPLASMS
ORAL CAVITY
PH VALUE
RATS
REDUCING AGENTS
REDUCTION
SENSITIVITY
VALENCE