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In vitro to in vivo extrapolation for decision-making
Citation:
Paul-Friedman, K. In vitro to in vivo extrapolation for decision-making. ISES 2021 Pre-Conference Continuing Education Course: Toxicokinetic New Approach Methodologies, NA, Virtual, August 13, 2021. https://doi.org/10.23645/epacomptox.16595735
Impact/Purpose:
Presentation to the International Society for Exposure Science Annual Meeting Pre-Conference Workshop on Toxicokinetic New Approach Methodologies (NAMs) August 2021. Toxicokinetics (TK) provides key information for relating inherent chemical hazard to the exposures that occur in order to understand potential risk posed to public health. The U.S. Environmental Protection Agency’s R package “httk” provides open source data and models with documentation of the model design, the input parameters, and the differential equations used to calculate tissue concentrations. Since high throughput toxicokinetics (HTTK) is the combination of in vitro data and generic TK modeling, the httk package contains tables of chemical specific data (>1000 for humans and >200 for rats) as well as a suite of generic TK models that may be parameterized with those data. Although the PBTK models within httk may be used for diverse purposes, a primary application of httk is “reverse dosimetry” in vitro-in vivo extrapolation (IVIVE) for data generated by high throughput screening (such as ToxCast and Tox21). httk allows propagation of uncertainty and variability, including the generation of “virtual populations” of individual physiologies through Monte Carlo simulations that incorporate physiologies, incorporating correlations curated from the scientific literature and biometric data from the US population from the Centers for Disease Control and Prevention (CDC) National Health and Nutrition Examination Survey (NHANES). This course will cover the generation of chemical-specific in vitro data for HTTK, generic models for key exposure scenarios that may be parameterized with those data, uncertainty and variability analysis, and applications to IVIVE.
Description:
This presentation is a training presentation aimed to describe the use of reverse dosimetry for in vitro to in vivo extrapolation of administered equivalent doses for in vitro bioactivity data. Topics covered include reverse dosimetry, the impacts of choices made in in vitro to in vivo extrapolation of dose, particularly using the R library "httk", and published case studies that demostrate the use of these administered equivalent doses in bioactivity:exposure ratios for prioritization and chemical assessments.
URLs/Downloads:
DOI: In vitro to in vivo extrapolation for decision-making
ISES_CE_IVIVE_FOR_PODS_KPF.PDF (PDF, NA pp, 5859.349 KB, about PDF)