TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 1422. HEALTH EFFECTSunstable inside the body and is ultimately reduced to chromium(III) in vivo by a variety of reducingagents. Chromium(V) and chromium(IV) are transient intermediates in this process.In vivo and in vitro experiments in rats indicated that, in the lungs, chromium(VI) can be reduced tochromium(III) by ascorbate. The reduction of chromium(VI) by ascorbate results in a shorter residencetime of chromium in the lungs and constitutes the first defense against oxidizing reagents in the lungs.When ascorbate is depleted from the lungs, chromium(VI) can also be reduced by glutathione. Thereduction of chromium(VI) by glutathione is slower and results in greater residence time of chromium inthe lungs, compared to reduction by ascorbate (Suzuki and Fukuda 1990). Other studies reported thereduction of chromium(VI) to chromium(III) by epithelial lining fluid (ELF) obtained from the lungs of15 individuals by bronchial lavage. The average reduction accounted for 0.6 µg chromium(VI)/mg ofELF protein. In addition, cell extracts made from pulmonary alveolar macrophages derived from fivehealthy male volunteers were able to reduce an average of 4.8 µg chromium(VI)/10 6 cells or 14.4 µgchromium(VI)/mg protein (Petrilli et al. 1986b). Metabolism of the chromium(VI) to chromium(III) bythese cell fractions significantly reduced the mutagenic potency of the chromium when tested in the Amesreversion assay. Postmitochondrial (S12) preparations of human lung cells (peripheral lung parenchymaand bronchial preparations) were also able to reduce chromium(VI) to chromium(III) (De Flora et al.1984). Moreover, large individual differences were observed (De Flora et al. 1984, 1987b), and extractsfrom pulmonary alveolar macrophages of smokers reduced significantly more chromium(VI) tochromium(III) than extracts from cells of nonsmokers. Because chromium(III) does not readily entercells, these data suggest that reduction of chromium(VI) by the ELF may constitute the first line ofdefense against toxicity of inhaled chromium compounds. Furthermore, uptake and reduction ofchromium compounds by the pulmonary alveolar macrophages may constitute a second line of defenseagainst pulmonary toxicity of chromium(VI) compounds. Microsomal reduction of chromium(VI) occursin the lungs mainly as it does in the liver, as discussed below.The first defense against chromium(VI) after oral exposure is the reduction of chromium(VI) tochromium(III) in the gastric environment where gastric juice (De Flora et al. 1987a) and ascorbate(Samitz 1970) play important roles. Studies using low-frequency electron paramagnetic resonance (EPR)spectrometry have shown that chromium(VI) is reduced to chromium(V) in vivo (Liu et al. 1994, 1995,1997a, 1997b; Ueno et al. 1995b). In vitro, low concentrations of ascorbate favor the formation ofchromium(V), whereas higher concentrations of ascorbate favor the formation of the reduced oxidationstate, chromium(III) (Liu et al. 1995). EPR spectrometric monitoring also showed that chromium(VI)was rapidly reduced to chromium(V) on the skin of rats, with a 3-fold greater response when the stratum