Hays SM, Kirman CR, Suh M, Proctor DM. 2014. Gastric reduction of hexavalent chromium [Cr(VI)] in fed and fasted human stomach samples. Presented at the Society of Toxicology’s 53rd Annual Meeting, March 23-27, Phoenix, AZ.
The rate and capacity of gastric reduction of hexavalent chromium [Cr(VI)] are important determinants of dose delivery of Cr(VI) to the small intestines, which in turn is a determinant of potential cancer risk. Our previous experiments using fed rodent gastric contents and fasted human fluid found that the reduction of Cr(VI) exhibited a mixed second-order reaction with a pH dependent second-order rate constant. Potential uncertainties regarding dilution which may affect the concentrations of reducing agents and the second-order rate constant were noted. This study is an extension to our previous experiments. Stomach fluid samples were obtained from human volunteers in the fed and fasted (paired) states. Using speciated isotope dilution mass spectrometry, studies were conducted to ascertain the kinetics (rates and capacity) of the various gastric fluids to reduce Cr(VI), with emphasis on better characterization of conditions during a fed state and characterizing inter-individual variability. The effects of pH, dilution and redox potential were investigated. Alternative mathematical forms of the reduction model were considered. The human data confirm a significant pH dependence for the second-order rate constant which appears to be independent of dilution. Fasted human gastric fluid has a lower pH (1.8±0.3) than pH in fed samples (2.7±0.7). In addition, fasted human gastric fluid has a lower capacity to reduce Cr(VI) per L stomach fluid (approximately half) as compared to fed gastric fluid. The results of these experiments are used to support human health risk assessment by modeling the extent of Cr(VI) escaping reduction in the stomach during fed and fasted states.