title: Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity.
abstract: Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6μgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3μgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8μgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water.
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: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy. Electronic address: Anna.Fiorenza.Camoirano@unige.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Camoirano
authors.affiliation: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy. Electronic address: rosannamicale@yahoo.it.
authors.forename: Rosanna T
authors.initials: RT
authors.lastname: Micale
authors.affiliation: Department of Health Sciences, University of Genoa, 16132 Genoa, Italy. Electronic address: lamaestra78@yahoo.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: La Maestra
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy. Electronic address: vsavarin@unige.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Savarino
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy. Electronic address: Patrizia.Zentilin@unige.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zentilin
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy. Electronic address: emarabotto@libero.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Marabotto
authors.affiliation: ToxStrategies, Mission Viejo, CA 92692, USA. Electronic address: msuh@toxstrategies.com.
authors.forename: Mina
authors.initials: M
authors.lastname: Suh
authors.affiliation: ToxStrategies, Mission Viejo, CA 92692, USA. Electronic address: dproctor@toxstrategies.com.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Proctor
mesh_terms: D000328:Adult; D002857:Chromium / Q000737:chemistry* / Q000633:toxicity; D005215:Fasting; D005750:Gastric Juice / Q000737:chemistry*; D006639:Histidine / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016296:Mutagenesis; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000737:chemistry* / Q000633:toxicity
chemical_list: D014874:Water Pollutants, Chemical; D002857:Chromium; C074702:chromium hexavalent ion; D006639:Histidine
keywords: Colorimetric method; Drinking water; Gastric fluid; Hexavalent chromium; Mutagenicity test