Influence of metal mixtures on co-occurring toxic metal bioavailability and effects in adult and developing deer mice
McBride, Tobias J.
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The bioaccessibility, bioavailability, and bioaccumulation of inorganic metals are complex principles. Unlike organic xenobiotics, many metals are required for biological functions. Nonetheless, dramatically increased concentrations of any metal may interact adversely with biomolecules, initiating a toxicological response when above a certain concentration in the organism. The bioavailability of environmental metals depends not only on metal concentrations in relevant matrices (food, water, soil), but on the chemical/physical form in which metals occur, the concentrations of other metals which co-occur, and the physiological status of the individual. Studies of mixed metal and metalloid (As, Cd, Cu, Pb and Zn) exposure in deer mice (Peromyscus maniculatus) at the Anaconda Smelter Site demonstrated that accumulation and biomarkers did not respond to the extent anticipated based on individual metal levels alone. This dissertation focuses on factors influencing the uptake, accumulation and resultant health effects of inorganic metals in a ubiquitous wild rodent species, and attempts to explain results from an earlier wildlife assessment on an NPL Superfund site. We sought to explain the variability in the effects of Pb exposure seen with the extreme heterogeneity of co-occurring metal contaminants in site soils. Using soil feeding studies, we have dissected the roles of Cu and Zn in modulating Pb absorption and Zn's role in reactivating ALAD activity in mice receiving high Pb doses. Second, our focus involves a lifetime bioaccumulation study of mice that investigated lactational metal exposure through the first 21 days of life (from soil-dosed feed provided to dams), and follows accumulation through 100 days of life. Comparisons with studies where adult mice were fed soil metals in their diet demonstrated that the more realistic lifetime exposure approach changes the accumulation kinetics, leading to greater accumulation of Cd and As, while underestimating exposures to Pb in the younger individuals. Finally, we investigate the role of lactation in weanling metal bioaccumulation, demonstrating how lactation decreases the dam's metal accumulation, while significantly increasing As and Pb exposure risks to the developing young.