ABSTRACT
An essential trace metal in its trivalent form, chromium in low concentrations is environmentally ubiquitous and vital for several important biological processes. At high concentrations, on the other hand, particularly in the hexavalent state, chromium is toxic, genotoxic, and carcinogenic in animals and humans. Many barriers exist, however, that limit the uptake and distribution of the element in its more toxic hexavalent form. The most effective detoxification process is its reduction to poorly absorbed Cr3 in the reducing environments found in body tissues and fluids such as saliva, gastric juice, gastrointestinal bacteria, blood plasma, or the liver (1). Direct inhalation of hexavalent chromium compounds resulting from certain industrial activities appears to comport the highest risk of tumor formation (2). As observed with lead, chromium can exchange between plasma and contacting bone surfaces to be ultimately incorporated into actively mineralizing bone (3). Normally, intake of the element occurs through the diet: highest levels are found in thyme (10 mg/g), black pepper (3.3 mg/g), and cloves (1.5 mg/g); the mean level seen in fish and red meat is 0.11 mg/g. Most hexavalent chromium taken in with food is reduced in the acid medium of the stomach to the trivalent form (4,5), severely limiting its ultimate uptake [average, 6.9% (6)]. Trivalent chromium increases glucose tolerance, acting as a cofactor with insulin to promote glucose utilization (7), and enhances lipid synthesis (8). Of the many oxidation states of chromium, Cr(III) and Cr(VI) are the most stable and prevalent in living organisms. Trivalent chromium is the prevalent form of the metal occurring in mineral deposits (chromite ores). An industrial hazard, Cr(VI) is absorbed by oral, respiratory, and skin routes. Many hexavalent chromium compounds, mostly oxides or oxohalides, are corrosive, primary irritants (9), sensitizers (10), and respiratory carcinogens (11,12). In vitro cytotoxicity studies using human keratinocytes show that Cr(VI) is more toxic than Cr(III), attributed to its greater membrane diffusivity and oxidizing potential. Cr(VI) can be reduced to the less damaging Cr(III) species by cysteine or glutathione, and
most notably by ascorbic acid (13). Dependent on pH, Cr(VI) exists as either the chromate (pH 6) or dichromate form (pH 2-6). On a relative scale of metal carcinogenicity, based on human and animal data, and calculations from acute exposure predictive models, chromium compounds were ranked highest in activity, comparable to nickel (14).
