Journal
SCIENCE OF THE TOTAL ENVIRONMENT
Volume 615, Issue -, Pages 150-160Publisher
ELSEVIER
DOI: 10.1016/j.scitotenv.2017.09.033
Keywords
pKa; High throughput; Ionization; Volume of distribution; PBPK
Categories
Funding
- Oak Ridge Institute for Science and Education [EPA-ORD/NCCT-2012-05]
- U.S. Environmental Protection Agency through its Office of Research and Development
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Chemical ionization plays an important role in many aspects of pharmacokinetic (PK) processes such as protein binding, tissue partitioning, and apparent volume of distribution at steady state (Vdss). Here, estimates of ionization equilibrium constants (i.e., pKa) were analyzed for 8132 pharmaceuticals and 24,281 other compounds to which humans might be exposed in the environment. Results revealed broad differences in the ionization of pharmaceutical chemicals and chemicals with either near-field (in the home) or far-field sources. The utility of these high-throughput ionization predictions was evaluated via a case-study of predicted PK Vdss for 22 compounds monitored in the blood and serumof the U.S. population by the U.S. Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES). The chemical distribution ratio between water and tissue was estimated using predicted ionization states characterized by pKa. Probability distributions corresponding to ionizable atom types (IATs) were then used to analyze the sensitivity of predicted Vdss on
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