Cited by 1,132Chromium effects and bioremediationCarcinogens and Genotoxicity AssessmentWater Treatment and Disinfection

Chromium in Drinking Water: Sources, Metabolism, and Cancer Risks

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Zhitkovich, Anatoly·2011·Chemical Research in Toxicology

Abstract

Drinking water supplies in many geographic areas contain chromium in the +3 and +6 oxidation states. Public health concerns are centered on the presence of hexavalent Cr that is classified as a known human carcinogen via inhalation. Cr(VI) has high environmental mobility and can originate from anthropogenic and natural sources. Acidic environments with high organic content promote the reduction of Cr(VI) to nontoxic Cr(III). The opposite process of Cr(VI) formation from Cr(III) also occurs, particularly in the presence of common minerals containing Mn(IV) oxides. Limited epidemiological evidence for Cr(VI) ingestion is suggestive of elevated risks for stomach cancers. Exposure of animals to Cr(VI) in drinking water induced tumors in the alimentary tract, with linear and supralinear responses in the mouse small intestine. Chromate, the predominant form of Cr(VI) at neutral pH, is taken up by all cells through sulfate channels and is activated nonenzymatically by ubiquitously present ascorbate and small thiols. The most abundant form of DNA damage induced by Cr(VI) is Cr-DNA adducts, which cause mutations and chromosomal breaks. Emerging evidence points to two-way interactions between DNA damage and epigenetic changes that collectively determine the spectrum of genomic rearrangements and profiles of gene expression in tumors. Extensive formation of DNA adducts, clear positivity in genotoxicity assays with high predictive values for carcinogenicity, the shape of tumor-dose responses in mice, and a biological signature of mutagenic carcinogens (multispecies, multisite, and trans-sex tumorigenic potency) strongly support the importance of the DNA-reactive mutagenic mechanisms in carcinogenic effects of Cr(VI). Bioavailability results and kinetic considerations suggest that 10-20% of ingested low-dose Cr(VI) escapes human gastric inactivation. The directly mutagenic mode of action and the incompleteness of gastric detoxification argue against a threshold in low-dose extrapolation of cancer risk for ingested Cr(VI).

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  • Cr(VI) is known to induce lung cancer, skin irritation, and damage to kidneys, livers, and gastric systems.

    “Cr(VI) is known to induce lung cancer, skin irritation, and damage to kidneys, livers, and gastric systems2,4.”

    From Optimized removal of hexavalent chromium from water using spent tea leaves treated with ascorbic acid (2022) · cites this paper as [4]

    The Epidemiological Studies and Conclusions sections support the lung-cancer claim: the paper reports increased respiratory cancer risk after occupational Cr(VI) inhalation. Animal Studies reports intestinal tumors and inflammatory cell infiltrates in the liver of exposed rodents, but does not establish the claimed gastric or liver damage in humans. The cited passages do not support skin irritation or kidney damage; the skin finding concerns tumors in UV-irradiated mice, not irritation. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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  1. Borges K. M.; Boswell J. S.; Liebross R. H.; Wetterhahn K. E. (1991) Activation of chromium(VI) by thiols results in chromium(V) formation, chromium binding to DNA and altered DNA conformation. Carcinogenesis 12, 551–561. 1849467

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Authors
Zhitkovich, A.
Affiliations
Brown University (US)
Corresponding author
Zhitkovich, Anatoly
Venue
Chemical Research in Toxicology
Published
2011-07-28
Volume
24
Issue
10
Pages
1617-1629
ISSN
  • 0893-228X (ISSN-L)
  • 1520-5010
OpenAlex
W2091102871
Cited by
1,132
References
141
Citations by year
2026: 73 · 2025: 80 · 2024: 124 · 2023: 112 · 2022: 135 · 2021: 110 · 2020: 100 · 2019: 88 · 2018: 74 · 2017: 47 · 2016: 40 · 2015: 46 · 2014: 44 · 2013: 29 · 2012: 25
FWCI
3.20
Type
journal article
Language
en
Open access
Locations
  • Chemical Research in Toxicology (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Environmental Health Sciences
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chromium effects and bioremediation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Water Treatment and Disinfection
Keywords
hexavalent chromium, drinking water contamination, chromium metabolism, DNA adducts, genotoxicity, carcinogenesis, gastric cancer, DNA damage, epigenetic modifications, low-dose extrapolation, carcinogen risk assessment, manganese oxide
MeSH terms
Animals, Carcinogens, Environmental, Chromium, DNA Damage, Gastric Mucosa, Gastrointestinal Neoplasms, Humans, Mutagens, Oxidation-Reduction, Risk Factors, Water Pollutants, Chemical, Drinking Water

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