Subtoxic intracellular trivalent chromium is not mutagenic: implications for safety of chromium supplementation.

For reasons that are outlined, toxicologists have long suspected that intranuclear trivalent chromium mediates much if not all of the well-documented genotoxicity of hexavalent chromium. However, more recent evidence suggests that this genotoxicity is in fact attributable to free radical damage catalyzed by hexavalent chromium under reducing aerobic conditions. Subtoxic intranuclear concentrations of trivalent chromium, while they can be clastogenic in vitro, do not appear to induce point mutations and thus are unlikely to mediate the carcinogenicity of hexavalent compounds. Furthermore, there is considerable doubt that sublethal doses of trivalent chromium can produce tissue levels high enough to induce clastogenic damage in vivo. These considerations elucidate the virtual non-toxicity of orally-administered trivalent chromium in any dose, and strongly suggest that dietary supplementation with trivalent chromium in reasonable amounts is unlikely to carry any genotoxic risk. However, further animal studies are advisable to rule out the possibility of clastogenicity when grossly 'megadose' amounts are ingested.