Submitted to: Free Radicals in Biology and Medicine
Publication Type: Peer reviewed journal
Publication Acceptance Date: 11/15/2006
Publication Date: 6/30/2006
Citation: Anderson, R.A., Hininger, I., Benaraba, R., Osman, M., Faure, H., Roussel, A. 2006. Safety of Trivalent Chromium Complexes Used in Nutrient Supplements: No Evidence For DNA Damage In Human HACAT Keratonocytes. Free Radicals in Biology and Medicine. 42: 1759-1765. Interpretive Summary:
Technical Abstract: Toxicity studies regarding trivalent chromium have often been completed under conditions that are not designed to reflect conditions that would be encountered under normal physiological conditions. The objective of this study was to evaluate the cytotoxic and genotoxic potential of the trivalent chromium complexes, histidinate, picolinate, and chloride, that are used in nutrient supplements. The highest doses that did not result in cytotoxic effects in human cultured HaCaT keratinocytes were 250 µM for Cr chloride and Cr histidinate and 120 µM for Cr picolinate. The LC50 was 50µM for hexavalent sodium dichromate and more than 120-fold higher for Cr chloride (6mM) and Cr histidinate (10mM). For Cr picolinate, at the saturating concentration (120 µM), the LC50 was not attained. In cells pre-incubated for 24h with trivalent forms of chromium and then submitted to H202 - induced oxidative stress, there was no evidence for pro-oxidant effects. In contrast, there were significant protective effects on DNA oxidative damage monitored by a decrease in % tail moment in the Comet assay when cells were pre-incubated with Cr histidinate, Cr picolinate, and Cr chloride at 50 and 5 µM. After 24h incubation with Cr chloride (250µM), Cr histidinate (250µM), and Cr picolinate (120µM), these high metal concentrations did not cause DNA damage. These data, obtained using human cultured HaCaT keratinocytes, demonstrate the lack of genotoxicity of Cr(III) forms used in dietary supplements and highlight the methodological limits of the studies using cell free systems or purified DNA to demonstrate the potential toxicity of nutritional chromium supplements.