Neurotoxic Interactions of Different Forms of Mercury

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DESCRIPTION (provided by applicant): Public anxieties about mercury exposure have been aroused by reports about the hazards of fish consumption, dental amalgams, and preservatives in vaccines. Although scientific support for such concerns may be tenuous, it is also true that sizable gaps remain in our understanding of mercury neurotoxicity, especially with respect to combined exposures to different species, a commonplace condition. The two forms that present the greatest health risks are methylmercury, found in fish and marine mammals, and metallic mercury vapor, found in industry, cosmetics, and dental amalgams. Mechanistic analyses and limited experimental data indicate that co-exposure to the two forms may enhance the neurotoxicity of either alone, an especially worrisome outcome for the developing brain. Because joint exposure is such a common occurrence, with assays in pregnant women indicating that the inorganic form accounts for more than 25% of mercury in blood, this project is designed to more clearly define the associated risks to brain development. Pregnant rats will be exposed concurrently to mercury vapor by inhalation and to methylmercury in drinking water. Neurobehavioral measures in the offspring will include schedule-controlled operant behavior to assess cognitive behavior, motivation, and memory; hindlimb splay as an assay for motor function; and locomotor activity, a common assay for neurobehavioral status. Mercury concentrations in offspring brains will also be measured. The research will proceed in stages. (1) Exposure levels will produce mild to moderate degrees of neurotoxicity and reliable dose-effect functions for each form by itself. (2 and 3) Here we determine if a specified concentration of vapor changes the dose-effect function for methylmercury and if a specified dose of methylmercury alters the concentration-effect function of mercury vapor. These results will be used to calculate, by Benchmark Dose modeling, vapor and methyl exposures inducing a 10% and 25% change in the neurotoxic indices. (4) The combined effects of these levels will be determined. The acquisition of these data offers a firm foundation for determining the risks to neurobehavioral development of concurrent exposures to both mercury species.