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Estimating Lead (Pb) Bioavailability In A Mouse Model
Thomas, D., P. Alava, K. Bradham, C. Nelson, AND J. Misenheimer. Estimating Lead (Pb) Bioavailability In A Mouse Model. Society of Toxicology Annual Meeting, New Orleans, LA, March 13 - 17, 2016.
This is an abstract for a poster presentation submitted for the 2016 annual meeting of the Society of Toxicology.
Children are exposed to Pb through ingestion of Pb-contaminated soil. Soil Pb bioavailability is estimated using animal models or with chemically defined in vitro assays that measure bioaccessibility. However, bioavailability estimates in a large animal model (e.g., swine) can be costly and laborious and bioaccessibility estimates require validation with bioavailability data. Here, we estimated Pb bioavailability from data on tissue Pb distribution after an 8-day exposure of adult female C57BL/6 mice to AIN-93G rodent diet amended with a reference compound, Pb acetate, or NIST-SRM2710a (Montana Soil). At termination, Pb levels were determined in tissues (liver, kidney, blood) in which Pb exerts deleterious effects and bone, the major depot for this metal. For each test material, 4 diets were prepared with Pb concentrations ranging from 3 to 30 µg/g. For Pb acetate or SRM2710a, significant linear relations were found between cumulative amounts of Pb ingested and tissue Pb concentrations. Relative bioavailability (RBA) of Pb in SRM2710a was estimated as ratios of slopes of regression lines describing the relation between cumulative Pb ingestion and tissue Pb concentration for the test materials. This approach yielded 4 estimates of the RBA of Pb in SRM2710a: bone, 0.34; blood, 0.49; kidney, 0.97; liver, 0.65. The estimated mean RBA of Pb was 0.61 (0.27 standard deviation). We also examined relations between Pb concentration in blood and tissues. Here, blood Pb is posited as the proximate source of Pb accumulated by tissues and that the source of Pb in blood (Pb acetate or soil derived) does not affect Pb transfer from blood to tissue. For both test materials, similar linear regression equations described relations between blood Pb concentration and liver or bone Pb concentration. In contrast, the source of Pb in blood affected kidney Pb concentrations. For a given blood Pb level, mice exposed to SRM2710a attained higher kidney Pb concentrations than did mice exposed to Pb acetate. This discordant dosage dependency for tissue Pb distribution should be evaluated in development and validation of the mouse model for Pb bioavailability. (This abstract does not reflect US EPA policy.)