TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 1462. HEALTH EFFECTSsignificant DNA strand breakage and the 8-hydroxy guanosine adduct, which correlated with hydroxylradical production (Aiyar et al. 1989, 1991). Very little chromium(V) was generated by this pathway. Itwas postulated that the reaction of chromium(VI) with hydrogen peroxide produces tetraperoxochromium(V)species that act as a catalyst in a Fenton-type reaction producing hydroxyl radicals in whichchromium(V) is continuously being recycled back to chromium(VI). The regeneration of chromium(VI)through interactions with chromium(V) and hydrogen peroxide is consistent with the findings ofMolyneux and Davies (1995) (see Section 2.4.2). As discussed above, chromium(VI) is ultimatelyreduced to chromium(III) within the cell. Chromium(III) can form stable complexes with DNA andprotein (De Flora and Wetterhahn 1989) which is discussed further in Section 2.4.2.The mechanism for clearance of chromium(VI) once reduced inside the liver cell may involve achromium(III)-glutathione complex. The glutathione complex would be soluble through the cellmembrane and capable of entering the bile (Norseth et al. 1982). The complexing of chromium(III) toother ligands has been shown to make them more permeable to the cell membrane (Warren et al. 1981).Although chromium(III) complexes are generally considered to be inert, Shi et al. (1993) demonstratedthat free radicals could be generated from extremely high non-physiological concentrations of hydrogenperoxide and lipid hydroperoxides (t-butyl hydroperoxide and cumene hydroperoxide) in vitro at neutralpH in the presence of chromium(III) chloride. The reduction of peroxides may indicate thatchromium(III) is capable of being reduced to chromium(II) and is consistent with other findings that haveshown that cysteine and NADH are capable of reducing trivalent chromium. Later studies demonstratedthat chromium(III) could enhance the formation of hydroxyl radicals from superoxide, though to a lesserextent than chromium(VI), suggesting that chromium(III) can act as a catalyst for the Haber-Weiss cycle(Shi et al. 1998). Therefore, the presence of these naturally occurring substances and cellular lipidhydroperoxides formed in lipid metabolism may contribute to the generation of free radicals that could bepotentially genotoxic.2.3.4 Elimination and Excretion2.3.4.1 Inhalation ExposureNormal urinary levels of chromium in humans have been reported to range from 0.24–1.8 µg/L(0.00024–0.0018 mg/L) with a median level of 0.4 µg/L (0.0004 mg/L) (Iyengar and Woittiez 1988).Humans exposed to 0.05–1.7 mg chromium(III)/m 3 as chromium sulfate and 0.01–0.1 mg