Explore the Dosimetric Relationship between the Intake of Chemical Contaminants and Their Occurrence in Blood and Urine

A chemical's partitioning andbiotransformation propertiescontrol how its occurrence in blood or urine responds to the externalintake dose. The dosimetric relationshipbetween the human intake dose of achemical contaminant (an "external dose") and its concentrationsin bodily fluids such as blood and urine (related to an "internaldose"), often characterized by a dose-to-concentration ratio,has critical applications in exposure science, toxicology, and riskassessment, especially in the "new approach methods"era. However, there is a lack of a mechanistic, systematic understandingof how such a dosimetric relationship depends on fundamental chemicalproperties, such as partition coefficients and biotransformation half-lives.Here, we investigate this issue using a well-evaluated toxicokineticmodel, which links external and internal doses by quantifying theabsorption and elimination of chemicals. Results are visualized ina series of chemical partitioning space plots, whereby a chemical'sdose-to-concentration ratio can be approximately predicted based onits partitioning between air, water, and octanol phases. Our resultsindicate that when taken in equal doses, chemicals with low volatilityand moderate to high hydrophobicity exhibit the highest concentrationsin the blood, and chemicals undergoing significant biotransformationtend to exhibit lower concentrations in comparison to their counterpartsundergoing negligible biotransformation but possessing similar partitioningproperties. Chemicals with high hydrophilicity have the highest concentrationsin urine. Such revealed property dependence is similar for both adultsand children and for individuals with normal body weights and withobesity. Overall, insights gained from this study are important inpredicting blood and urinary concentrations from exposure informationand in determining the exposure rate that produces the blood or urinaryconcentrations observed in biomonitoring studies.