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theses

Risk assessors have utilized worst-case scenarios and the default assumption of 100% bioavailability to make ingestion exposure estimates. This leads to overestimation of risk by miscalculating the likelihood of a contaminant becoming bioavailable after exposure. Furthermore, bioavailability studies often involve animal models, which are time consuming and expensive. As a result, in vitro gastrointestinal models have been incorporated into risk characterization for the calculation of bioaccessibility. However, these models do not provide information on the effects of chemicals on the human body in the presence of low-level, chronic exposures, which are typical of environmental contaminants. The primary objectives of this research are two-fold: first, to examine how a cellular system is affected by heavy metal-contaminated soil after extraction by in vitro bioaccessibility techniques, and second to identify the utility of a hepatocellular model as a complementary tool for in vitro bioaccessibility models in risk assessment. The percent bioaccessibility measured for five metals, Pb, As, Cd, Ni and Cr, across nine soils, using an in vitro system that incorporated synthetic saliva, gastric and intestinal fluids, varied from <10% to nearly 100% with the bioaccessibility of most metals declining from the saliva/gastric fluid to the intestinal fluid due to the higher pH of the latter. However, no single generalization predicted the association across all metals in the various soils, indicative of the need to evaluate multiple metals’ bioaccessibility when estimating risk from ingestion of soil. Subsequent to in vitro extraction, the toxicity of the bioaccessible fraction of nine soils was assessed using an in vitro hepatocellular model. A multiple regression linear model that predicts hepatotoxicity from bioaccessible metal concentration accounted for more than 80% of the variability in our predictive model, highlighting the potential of exposing an in vitro hepatocellar (or other cell type) model to the bioaccessible fluid fraction derived from soil as a complimentary and precursor screening tool for more expensive in vivo examinations. Conversely, Ni only accounted for 26%, Cr for 28%, Pb for 0.4%, Cd for 2% and As for 11% of the model variability on an individual basis if toxicity of all metals are independent of each other. The use a human cellular system as a complimentary tool in risk assessment allows for the application of a mixed metal contaminant system as a more biologically relevant model than total metal content or metal bioaccessibility alone. Results from this study provided evidence of the utility of cellular model responses to bioaccessible fluids as a tool to evaluate contaminants since it examines mixture effects rather than single elements. Risk studies that evaluate exposure to mixtures of metals rather than individual metals better reflect real-world exposures to soils, which is of particular importance when assessing risk.

ETD_7235

Ph.D.

Includes bibliographical references

by Shavonne Nyoka Hylton

doi:10.7282/T3NZ89SQ

ETD doctoral

The author owns the copyright to this work.