Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

Journal Article · Thu Sep 01 04:00:00 EDT 2016 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2016.07.004· OSTI ID:22689258

Camoirano, Anna ^[1]; Savarino, Vincenzo ^[2]; Zentilin, Patrizia ^[2]; Marabotto, Elisa ^[2]; Suh, Mina ^[3]

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1. Department of Health Sciences, University of Genoa, 16132 Genoa (Italy)
2. Gastroenterology Unit, Department of Internal Medicine, University of Genoa, 16132 Genoa (Italy)
3. ToxStrategies, Mission Viejo, CA 92692 (United States)

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 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(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 ± 2.8 μg Cr(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 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. 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 ≤ 180 ppm Cr(VI) for up to 90 days 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. - Highlights: • Cr(VI) reduction capacity was greater in post-meal than paired pre-meal samples. • Cr(VI) reduction was rapid, pH dependent, and due to heat stable components. • Gastric fluid attenuates the mutagenicity of Cr(VI) and reduces risk of GI cancer. • The results are useful to quantitatively evaluate the fate of ingested Cr(VI).

• OSTI ID: 22689258
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 306; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATTENUATION
CHROMIUM
DNA
DNA DAMAGES
DPCA
DRINKING WATER
GASTROINTESTINAL TRACT
HAZARDS
ISOTOPE DILUTION
MASS SPECTROSCOPY
MUTAGEN SCREENING
NEOPLASMS
PH VALUE
REDUCTION
RISK ASSESSMENT
RODENTS