Comparison of physiologically based pharmacokinetic modeling platforms for developmental neurotoxicity in vitro to in vivo extrapolation

This study describes an in vitro to in vivo extrapolation (IVIVE) approach to derive human-relevant administered equivalent doses based on chemical partitioning into developmental neurotoxicity (DNT) target organs during the critical period of brain development. Three physiologically based pharmacokinetic (PBPK) modeling platforms were evaluated for their suitability for this DNT-IVIVE approach. This dataset includes the model code for the two open-source platforms used for this approach- the U.S. EPA's R package, httk, and PK-Sim from Open Systems Pharmacology.
, PBPK modeling was performed in batch mode in each platform using a pregnancy model at 15 gestation weeks (GW) and 24GW. For modeling of infants, a standard PBPK model was run at 2 weeks and 6 months of age for each platform; for httk, this was the preliminary brain—adipose model described in Unnikrishnan et al. (2024) (Unnikrishnan. et al. in prep). The individual for simulation was created based on age for PK-Sim, which accounts for ontogeny. As httk does not consider ontogeny, age was set in httk by body weight using the GastroPlus (Simulations Plus) default weights for a 2 week and 6 month-old male, which were 3.7 kg and 8.29 kg, respectively. Chemical exposure was modeled as a single oral bolus of 1 mg/kg body weight and was simulated for a 24-hour period. As the maximum number of integration steps that GastroPlus can run in batch mode is 500, the integration time interval was divided into 500 steps for all platforms to ensure equivalent granularity across platforms for estimation o..., # Acute exposure batch PBK simulations for pregnancy and neonates

## Project description

The files housed here were created for the manuscript \"Comparison of physiologically based pharmacokinetic modeling platforms for developmental neurotoxicity in vitro to in vivo extrapolation.\" In this work, an in vitro to in vivo extrapolation (IVIVE) approach for developmental neurotoxicity (DNT) was developed using physiologically based pharmacokinetic (PBPK) modeling. The included files were used for modeling in two of the three PBPK models used in this publication- PK-Sim and httk. Modeling was performed in batch for neonates (2 weeks and 6 months) and pregnancy (GW 15 and 24) for oral exposure.

## Description of the project

*PK-Sim*

This is a R project (Pregnancy and Pediatric batch run.Rproj) that uses R environment (renv). The files .gitignore, .Rprofile and renv.lock are all files related to renv or git. This R project requires the installation of ospsuiteR package. To do so, use:

ins..., ,