The effect of inorganic or organic metals and metal complexes is of particular interest to the NTP because of their prevalence in drinking water and industrial processes, use as constituents in anticancer drugs, and their diverse target organ toxicities. Mechanisms of cellular immunotoxicity were studied in rats or mice exposed to mercuric chloride, nickel sulfate or titanocene dichloride. Tissue accumulation of these metals in target organs indicated the sensitivity of the biochemical assays to evaluate target organ toxicity which often preceeded gross, microscopic or clinical methods. Development of animal models to study Fischer rat leukemia revealed tumor markers for this disease that can be use to distinguish between age-induced and chemically-enhanced leukemogenesis. Urinary enzyme responses to nephrotoxic chemical insult were evaluated to use as a model to predict renal toxicity in chronic studies. Enzymatic method development to enhance stability, sensitivity, and efficiency of 7-ethoxycoumarin-ortho-demethylase was initiated to evaluate MFO-initiating activity of chemicals in minute amounts of rodent tissue.
