Explore the Dosimetric Relationship Between Intake of Chemical Contaminants and Their Occurrence in Blood and Urine
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Authors
Olsen, Amy
Issue Date
2023
Type
Thesis
Language
Keywords
Alternative Title
Abstract
The dosimetric relationship between the human intake of a chemical contaminant (an “external dose”) and its concentrations in bodily fluids such as blood and urine (related to an “internal dose”), often characterized by a dose-to-concentration ratio, has critical applications in exposure science, toxicology, and risk assessment, especially in the “new approach methods” era. However, there is a lack of a mechanistic, systematic understanding of how such a dosimetric relationship depends on fundamental chemical properties, such as partition coefficients and biotransformation half-lives. Here, we investigate this issue using a well-evaluated toxicokinetic model, which links external and internal doses by quantifying the absorption and elimination of chemicals. Results are visualized in a series of chemical partitioning space plots, whereby a chemical’s dose-to-concentration ratio can be approximately predicted based on its partitioning between air, water, and octanol phases. Our results indicate that when taken in equal doses, chemicals with low volatility and moderate to high hydrophobicity exhibit the highest concentrations in blood, and chemicals undergoing significant biotransformation tend to exhibit lower concentrations in comparison to their counterparts undergoing negligible biotransformation but possessing similar partitioning properties. Chemicals with high hydrophilicity have the highest concentrations in urine. Such revealed property dependence is similar for both adults and children, and for individuals with normal body weights and with obesity. Overall, insights gained from this study are important in predicting blood and urinary concentrations from exposure information and in determining the exposure rate that produces the blood or urinary concentrations observed in biomonitoring studies.