| Autor: |
Bianchi, Enrica, Costa, Eduardo, Harrill, Joshua, Deford, Paul, LaRocca, Jessica, Chen, Wei, Sutake, Zachary, Lehman, Audrey, Pappas-Garton, Anthony, Sherer, Eric, Moreillon, Connor, Sriram, Shreedharan, Dhroso, Andi, Johnson, Kamin |
| Zdroj: |
Journal of Agricultural and Food Chemistry; 20240101, Issue: Preprints |
| Abstrakt: |
Utilization of in vitro(cellular) techniques, like Cell Painting and transcriptomics, could provide powerful tools for agrochemical candidate sorting and selection in the discovery process. However, using these models generates challenges translating in vitroconcentrations to the corresponding in vivoexposures. Physiologically based pharmacokinetic (PBPK) modeling provides a framework for quantitative in vitroto in vivoextrapolation (IVIVE). We tested whether in vivo(rat liver) transcriptomic and apical points of departure (PODs) could be accurately predicted from in vitro(rat hepatocyte or human HepaRG) transcriptomic PODs or HepaRG Cell Painting PODs using PBPK modeling. We compared two PBPK models, the ADMET predictor and the httkR package, and found httkto predict the in vivoPODs more accurately. Our findings suggest that a rat liver apical and transcriptomic POD can be estimated utilizing a combination of in vitrotranscriptome-based PODs coupled with PBPK modeling for IVIVE. Thus, high content in vitrodata can be translated with modest accuracy to in vivomodels of ultimate regulatory importance to help select agrochemical analogs in early stage discovery program. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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