Kirman CR, Proctor DM, Suh M, Hays S. 2015. Reduction of hexavalent chromium by gastric fluids from fed and fasted individuals with applications to toxicokinetic modeling. Presented at the Society of Toxicology’s 54th Annual Meeting, March 22-26, San Diego, CA.
Previously, a simple model was developed to describe the pH-dependent reduction of hexavalent chromium (CrVI) by gastric contents from fasted individuals. In this study, the rates and capacities of CrVI reduction were characterized in gastric contents from fed volunteers (7 individual samples, 1 pooled sample) and fasted volunteers (5 individual samples). Reduction capacities were first estimated over a 4-hour reduction period. Thereafter, a dual-spike approach was used to help characterize the concentration- dependence of the 2nd order reduction rate constants: 1) spike 1 was added at the start of the incubation using low CrVI concentrations (~0.04-0.3 mg/L); 2) after 30 minutes, spike 2 was added to provide a characterization of higher concentrations (~1-3 mg/L), and the reaction was allowed to continue for a total of 150 minutes. To improve our understanding of CrVI reduction at higher pH levels, additional data were collected for gastric contents from proton-pump inhibitor users (3 individual samples, fasted, pH 5-7.5) and by artificially increasing pH from one fed individual (pH=2 adjusted to pH 4.7 and 5.8). Time-course data were analyzed using speciated isotope dilution mass spectrometry (SIDMS). These data, when combined with previously collected data, were well described by a 2-pool model (pool 1 =fast rate with low capacity; pool 2 = slower rate with higher capacity). These data support conclusions that: 1) human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents; and 2) low concentrations of CrVI are reduced more rapidly than are high concentrations of CrVI. With the combined data set, several pH-dependent forms of the model were considered and will be discussed.