STP1226

    Design of Pharmacokinetic and Bioavailability Studies of Lead in an Immature Swine Model

    Published: Jan 1995


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    Abstract

    We have designed and implemented a series of investigations aimed at estimating the range and extent of gastrointestinal absorption of lead from various mineralogical matrices following oral and intravenous reference substance doses and oral test substance doses. Using pharmacokinetic information from our previous work [1, 2] we are employing immature swine as a plausible, in vivo mammalian model for lead absorption in juvenile children [3]. This paper describes the rationale for the experimental design used to characterize the dose and time dependence of lead absorption over a subchronic (∼30 day) period. Four dose groups ranging from 25 μg/kg/day to 675 μg/kg/day were used to validly characterize the oral absorption of a soluble lead reference substance, lead acetate (PbAc2·3H2O) . Based on those results, oral doses ranging from 90 μg/kg/day to 1400 μg/kg/day, were planned to characterize the absorption of a test soil substance derived from residential soil in an active non-ferrous mining and historical smelting area of the Rocky Mountain west. Test substances employed were fully characterized as to lead concentration, geochemistry, and mineral matrix.

    Keywords:

    lead, bioavailability, absorption, pharmacokinetics, gastrointestinal, uptake, swine, metal, mining, smelting, soil, contamination


    Author Information:

    Weis, CP
    Regional Toxicologist, U.S. Environmental Protection Agency-Region VIII, Denver, CO

    Poppenga, RH
    Assistant Professor, Michigan State University, East Lansing, MI

    Thacker, BJ
    Associate Professor, Michigan State University, East Lansing, MI

    Henningsen, GM
    Regional Toxicologist, U.S. Environmental Protection Agency-Region VIII, Denver, CO

    Curtis, A
    Chief, U.S. Environmental Protection Agency-Region VIII, Denver, CO


    Paper ID: STP12962S

    Committee/Subcommittee: E06.23

    DOI: 10.1520/STP12962S


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