CELLULAR BIOCHEMISTRY STUDIES ON CHEMICAL SELECTED FOR EVALUATION BY NTP

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The effect of inorganic or organic metals and metal complexes is of particular interest because of their prevalence in drinking water and industrial processes, use as constituents in anticancer drugs, and their diverse target organ toxicities. Toxicological studies of various, selected metallic salts are being conducted to support and extend the results obtained at contract test facilities. Blood and target organ levels are measured to determine the disposition and steady state concentrations of the metal residues. Cellular biochemical responses provided sensitive indices of target organ toxicity that often preceeded clinical signs or microscopic evidence of pathology. Examples included mercury inhibition of glycolytic enzymes in thymic T-cells in association with immunotoxicity, and nickel inhibition of hexose monophosphate shunt enzymes in granulocyte/macrophage stem cells from bon marrow in association with myelotoxicity. Further studies are underway with titanocene dichloride, sodium chromate, zinc potassium chromate, chromium carbonyl, and ferric ammonium ferrocyanide.