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New research indicates that chromium (III) is even more genotoxic than chromium (VI)


Chromium (III) is often discussed as an essential element that is believed to play a beneficial role in the glucose metabolism and therefore is included in some food supplements and health products. However, naturally available food sources used in well-balanced diets are capable to cover the requirement of trivalent chromium completely and Cr deficiency cases are therefore extremely rare. While evidence-based biochemical justification for artificial source needed additionally to standard foods has not been provided in the literature,  some commercial organisations promote Cr3+ nutrient supplements. During the last decades, chromium has become the second most popular dietary supplement after calcium in the United States with sales amounting to approximately 100 million dollars annually. While chromium supplements are mainly used for weight loss, some patients with diabetes also use these supplements to improve their glycemic control. However, efficacy of chromium to improve glycemic control has not been established. On the other side, hexavalent chromium  is classified to be carcinogenic. Therefore, during the last decade, a bunch of rules and legislation has been established, meant to restrict the exposure of humans to hexavalent chromium (see EVISA's Link database).

The new study:
In this new study, chinese researchers compared the effects of Cr(VI) (i.e., CrO3) and Cr(III) (i.e., CrCl3) on DNA damage both in vivo and in vitro using yeast and human T cell leukemia Jurkat cells as well as animal cells. Their  in vivo results suggest that both Cr(VI) and Cr(III) significantly induce genetic mutation in yeast and cause DNA damage within both yeast and Jurkat cells and that both can act as genotoxic compounds. In addition, the ability of CrCl3 to generate DNA damage is significantly greater than that of CrO3.

The researchers conclude "Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo."   

Chromium III and chromium VI render toxicity via different mechanisms.  Previous studies on chromium genotoxicity mainly focused on the formation of chromium-DNA adducts. The researchers found that chromium III interferes with base pair stacking and causes DNA cleavage and degradation of DNA. Cr(VI) was previously suggested to interact with DNA via two modes of interaction: inducing structural changes and DNA compaction. Results obtained from the new study further indicates that Cr(VI) can intercalate into the planes between DNA base pairs and cause DNA structural changes and degradation.

The new study:

Zhijia Fang, Min Zhao, Hong Zhen, Lifeng Chen, Ping Shi, Zhiwei Huang, Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro, PLoS ONE, 9/8 (2014) e103194. doi: 10.1371/journal.pone.0103194

Related studies:

Z. Huang, Xin Kuang, H. Zhen, L. Zhou, P. Shi, Comparative studies of tri- and hexavalent chromium cytotoxicity and their effects on oxidative state of Saccharomyces cerevisiae cells, Curr. Microbiol., 68 (2014) 448–456. doi: 10.1007/s00284-013-0496-1

Olga Golubnitschaja, Kristina Yeghiazaryan, Opinion controversy to chromium picolinate therapy’s safety and efficacy: ignoring ‘anecdotes’ of case reports or recognising individual risks and new guidelines urgency to introduce innovation by predictive diagnostics?, EPMA J., 3 (2012) 11.  doi:10.1186/1878-5085-3-11

David A. Eastmond, James T. MacGregor and Ronald S. Slesinski, Trivalent chromium - Assessing the genotoxic risk of an essential trace element and widely used human and animal nutritional supplement, Crit. Rev. Toxicol., 38/3 (2008) 173-190. doi: 10.1080/10408440701845401

Aviva Levina, Peter A Lay, Chemical properties and toxicity of chromium(III) nutritional supplements, Chem. Res. Toxicol.. 21/3 (2008) 563-71. DOI: 10.1021/tx700385t

I. Hininger, R. Benaraba, M. Osman, H. Faure, R.A. Marie, et al., Safety of trivalent chromium complexes: no evidence for DNA damage in human HaCaT keratinocytes, Free Radic Biol Med 42 (2007)1759–65. doi: 10.1016/j.freeradbiomed.2007.02.034

M. Costa, C.B. Klein, Toxicity and carcinogenicity of chromium compounds in humans, Crit. Rev. Toxicol., 36 (2006) 155–163. doi: 10.1080/10408440500534032

E. Rudolf, M. Cervinka, Chromium (III) produces distinct type of cell death in cultured cells,  Acta Medica (Hradec Kralove) 46 (2003) 139–46.

D. Bagchi, S.J. Stohs, B.W. Downs, M. Bagchi, H.H. Preuss, Cytotoxicity and oxidative mechanisms of different forms of chromium, Toxicology, 180 (2002) 5–22. doi: 10.1016/s0300-483x(02)00708-4

A. Zhitkovich, V. Voitkun, M. Costa, Formation of the amino acid-DNA complexes by hexavalent and trivalent chromium in vitro: importance of trivalent chromium and the phosphate group, Biochem., 35 (1996) 7275–82. doi: 10.1021/bi960147w

E. Snow, A possible role for chromium (III) in genotoxicity, Environ. Health Perspect., 92 (1991) 75–81. doi: 10.1289/ehp.919275

Related Information

U.S. EPA: Toxicological review of trivalent chromium
National Institutes of Health: Chromium (Dietary Supplement Fact Sheet)
EFSA: Scientific Opinion on the safety of trivalent chromium as a nutrient added for nutritional purposes to foodstuffs for particular nutritional uses and foods intended for the general population (including food supplements)

Related EVISA Resources

EVISA Link database: Toxicity of chromium valency species
EVISA Link database: Legislation related to hexavalent chromium
EVISA Brief Summary: Speciation and Toxicity

Related EVISA News

August 24, 2013: California proposes new hexavalent chromium standard for drinking water
March 14, 2013: Chromate in food samples: an artefact of wrongly applied analytical methodology
April 11, 2012: EPA calls for more study on hexavalent chromium in drinking water
May 25, 2011: Oral ingestion of hexavalent chromium through drinking water and cancer mortality
June 12, 2010: Chromium(VI) much more toxic than chromium(III): At least for freshwater algae a paradigm to revise?
May 17, 2007: Hexavalent Chromium in Drinking Water Causes Cancer in Lab Animals
April 24, 2007: Nutrigenomics: The role of chromium for fat metabolism revisited
June 8, 2006: Scientific journal adds fuel to ongoing chromium debate
March 20, 2005: United Kingdom's Food Standards Agency granted derogation to Chromium (III) compounds as a food supplement
November 23, 2004: Chromium (III) - not only therapeutic?

last time modified: August 19, 2014


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