Simulating toxicokinetic variability to identify susceptible and highly exposed populations.

Autor: Breen M; Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC, USA., Wambaugh JF; Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC, USA., Bernstein A; Oak Ridge Institute for Science and Education (ORISE) fellow at the Center for Public Health and Environmental Assessment, Research Triangle Park, NC, USA., Sfeir M; Oak Ridge Institute for Science and Education (ORISE) fellow at the Center for Computational Toxicology and Exposure, Research Triangle Park, NC, USA., Ring CL; Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC, USA. Ring.Caroline@epa.gov.
Jazyk: angličtina
Zdroj: Journal of exposure science & environmental epidemiology [J Expo Sci Environ Epidemiol] 2022 Nov; Vol. 32 (6), pp. 855-863. Date of Electronic Publication: 2022 Nov 03.
DOI: 10.1038/s41370-022-00491-0
Abstrakt: 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.
(© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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