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Evaluation of lead and phosphate interactions in a mouse model for oral bioavailability of lead
Citation:
Elek, B., P. Alava, J. Misenheimer, C. Nelson, K. Bradham, AND D. Thomas. Evaluation of lead and phosphate interactions in a mouse model for oral bioavailability of lead. Society of Toxicology Annual Meeting, Baltimore, Maryland, March 12 - 16, 2017.
Impact/Purpose:
This abstract describes the evaluation of the effect of dietary phosphate level on the bioavailability of lead in a mouse model developed for determination of relative bioavailability of ingested metals and metalloids.
Description:
Exposure to lead (Pb) in early life has profound and deleterious effects on neurodevelopment in children. Pb in soil and dust are important sources of exposure for children. One important determinant of the extent of exposure to Pb through ingestion of soil or dust is its bioavailability in these media. Bioavailability is the fraction of metal present in ingested material that crosses the gastrointestinal barrier. This fraction of the ingested dose, which can range from 0 to 1, is available for systemic distribution and metabolism and toxic action. A model that uses young adult female C57BL/6 mice has been developed to assess the bioavailability of Pb in ingested soil. This mouse model provides estimates of bioavailability of Pb that are comparable to those obtained in the well-established juvenile swine model. The mouse model has been used to examine effects of dietary phosphate (P) on the bioavailability of Pb. Here, mice received powdered AIN-93G purified rodent diet amended with Pb (as Pb acetate) at levels ranging from about 3 to 30 parts per million. AIN-93G diets used in these studies contained P at a nutritionally sufficient level (0.3% w/w) or at a higher level (1.2%). Mice had free access to diets and water for 8 days before collection of tissues for measurement of Pb concentrations. Relative bioavailability of Pb in the high P diet was estimated as ratios of the slopes of regression lines for relations between cumulative Pb intake and concentration of Pb in tissues of mice that received Pb in the high P or sufficient P diet. For each tissue examined, there was a strong correlation (r >0.91) between the level of Pb in the tissue and the level of Pb in blood, the proximate source of Pb available for tissue uptake. Pb levels in tissues were also strongly correlated (r > 0.95) with cumulative intake of Pb. Point estimates of relative bioavailability of Pb in the high P diet based on relations for different tissues were kidney (0.67), liver (0.36), blood (0.47), and bone (0.27). These results suggest that increased P in diet reduced the bioavailability of ingested Pb and is consistent with earlier work on the antagonistic effect of P on Pb bioavailability in a variety of species, including humans. The mouse model may be useful for the systematic study of the effect of addition of P-containing amendments of bioavailability of Pb from contaminated soils and in studies of the mechanistic bases for interactions between P and Pb in the gastrointestinal tract. (This abstract does not reflect U.S. EPA policy).