High-throughput PBTK models for in vitro to in vivo extrapolation
| Autor: | John F. Wambaugh, Michael-Rock Goldsmith, Miyuki Breen, Caroline Ring, Anna Kreutz |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Toxicity data Computer science Potential risk Extrapolation Reproducibility of Results General Medicine Computational biology Toxicology Models Biological Risk Assessment 030226 pharmacology & pharmacy Article In vitro High-Throughput Screening Assays Toxicokinetics 03 medical and health sciences 0302 clinical medicine In vivo 030220 oncology & carcinogenesis Animals Humans Computer Simulation Throughput (business) |
| Zdroj: | Expert Opin Drug Metab Toxicol |
| ISSN: | 1744-7607 1742-5255 |
| Popis: | INTRODUCTION: Toxicity data are unavailable for many thousands of chemicals in commerce and the environment. Therefore, risk assessors need to rapidly screen these chemicals for potential risk to public health. High-throughput screening (HTS) for in vitro bioactivity, when used with high-throughput toxicokinetic (HTTK) data and models, allows characterization of these thousands of chemicals. AREAS COVERED: This review covers generic physiologically-based toxicokinetic (PBTK) models and high-throughput PBTK modeling for in vitro-in vivo extrapolation (IVIVE) of HTS data. We focus on “httk”, a public, open-source set of computational modeling tools and in vitro toxicokinetic (TK) data. EXPERT OPINION: HTTK benefits chemical risk assessors with its ability to support rapid chemical screening/prioritization, perform IVIVE, and provide provisional TK modeling for large numbers of chemicals using only limited chemical-specific data. Although generic TK model design can increase prediction uncertainty, these models provide offsetting benefits by increasing model implementation accuracy. Also, public distribution of the models and data enhances reproducibility. For the httk package, the modular and open-source design can enable the tool to be used and continuously improved by a broad user community in support of the critical need for high-throughput chemical prioritization and rapid dose estimation to facilitate rapid hazard assessments. |
| Databáze: | OpenAIRE |
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