Simulating toxicokinetic variability to identify susceptible and highly exposed populations
- 3 November 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Exposure Science & Environmental Epidemiology
- Vol. 32 (6), 855-863
- https://doi.org/10.1038/s41370-022-00491-0
Abstract
Background Toxicokinetic (TK) data needed for chemical risk assessment are not available for most chemicals. To support a greater number of chemicals, the U.S. Environmental Protection Agency (EPA) created the open-source R package “httk” (High Throughput ToxicoKinetics). The “httk” package provides functions and data tables for simulation and statistical analysis of chemical TK, including a population variability simulator that uses biometrics data from the National Health and Nutrition Examination Survey (NHANES). Objective Here we modernize the “HTTK-Pop” population variability simulator based on the currently available data and literature. We provide explanations of the algorithms used by “httk” for variability simulation and uncertainty propagation. Methods We updated and revised the population variability simulator in the “httk” package with the most recent NHANES biometrics (up to the 2017–18 NHANES cohort). Model equations describing glomerular filtration rate (GFR) were revised to more accurately represent physiology and population variability. The model output from the updated “httk” package was compared with the current version. Results The revised population variability simulator in the “httk” package now provides refined, more relevant, and better justified estimations. Significance Fulfilling the U.S. EPA’s mission to provide open-source data and models for evaluations and applications by the broader scientific community, and continuously improving the accuracy of the “httk” package based on the currently available data and literature.Keywords
This publication has 33 references indexed in Scilit:
- Incorporating High-Throughput Exposure Predictions With Dosimetry-AdjustedIn VitroBioactivity to Inform Chemical Toxicity TestingToxicological Sciences, 2015
- PBTK modelling platforms and parameter estimation tools to enable animal-free risk assessmentRegulatory Toxicology and Pharmacology, 2014
- Toxicokinetics as a key to the integrated toxicity risk assessment based primarily on non-animal approachesToxicology in Vitro, 2013
- The exposure data landscape for manufactured chemicalsScience of The Total Environment, 2012
- Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic modelArchives of Toxicology, 2011
- The Toxicity Data Landscape for Environmental ChemicalsEnvironmental Health Perspectives, 2009
- Transforming Environmental Health ProtectionScience, 2008
- The ToxCast Program for Prioritizing Toxicity Testing of Environmental ChemicalsToxicological Sciences, 2006
- Prediction of the Clearance of Eleven Drugs and Associated Variability in Neonates, Infants and ChildrenClinical Pharmacokinetics, 2006
- A standard nomenclature for structures of the kidneyKidney International, 1988