title: Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling.
abstract: To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (<0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment.
authors.affiliation: Summit Toxicology, Orange Village, OH, 44022, USA. Electronic address: ckirman@summittoxicology.com.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Kirman
authors.affiliation: ToxStrategies, Inc., Mission Viejo, CA, 92692, USA. Electronic address: msuh@toxstrategies.com.
authors.forename: Mina
authors.initials: M
authors.lastname: Suh
authors.affiliation: Summit Toxicology, Allenspark, CO, 8040, USA. Electronic address: shays@summittoxicology.com.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Hays
authors.affiliation: Brooks Applied Labs, Bothell, WA, 98011, USA. Electronic address: hakan@brooksrand.com.
authors.forename: Hakan
authors.initials: H
authors.lastname: Gürleyük
authors.affiliation: Brooks Applied Labs, Bothell, WA, 98011, USA. Electronic address: russ@brooksrand.com.
authors.forename: Russ
authors.initials: R
authors.lastname: Gerads
authors.affiliation: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy. Electronic address: sdf@unige.it.
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
authors.affiliation: Duke University Medical Center, Department of Surgery, Durham, NC, 27710, USA. Electronic address: william.parker@duke.edu.
authors.forename: William
authors.initials: W
authors.lastname: Parker
authors.affiliation: Duke University Medical Center, Department of Surgery, Durham, NC, 27710, USA. Electronic address: shu.lin@duke.edu.
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.affiliation: ToxStrategies, Inc., Katy, TX, 77494, USA. Electronic address: lhaws@toxstrategies.com.
authors.forename: Laurie C
authors.initials: LC
authors.lastname: Haws
authors.affiliation: ToxStrategies, Inc., Austin, TX, 78751, USA. Electronic address: mharris@toxstrategies.com.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Harris
authors.affiliation: ToxStrategies, Inc., Mission Viejo, CA, 92692, USA. Electronic address: dproctor@toxstrategies.com.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Proctor
mesh_terms: D002857:Chromium / Q000737:chemistry*; D005215:Fasting; D005750:Gastric Juice / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D014874:Water Pollutants, Chemical / Q000737:chemistry*
chemical_list: D014874:Water Pollutants, Chemical; D002857:Chromium; C074702:chromium hexavalent ion
keywords: Hexavalent chromium; Speciated Isotope Dilution Mass Spectrometry (SIDMS); human gastric fluid; stomach reduction kinetics