Data for: Data-Driven Evaluation of PBPK Models for Developmental Toxicity

Description

The material in this repository is related to the article entitled "Data-Driven Evaluation of PBPK Models for Developmental Toxicity" to be published in Data in Brief. The related article provides the physicochemical parameters of 10 compounds (bisphenol A, caffeine, carbamazepine, carbaryl, deltamethrin, ethanol, nicotine, thalidomide, and acetaminophen), as well as parameters characterizing their absorption, distribution, metabolism, and excretion (ADME) behavior following different scenarios of absorption. This set of parameters was used to implement a three-tiered pregnancy physiologically based pharmacokinetic (PBPK) model in Berkeley Madonna version 10.5.1 and R. Human toxicokinetic studies from the literature were used to calibrate and validate the PBPK model. This repository contains the R files used for the global sensitivity analysis (ZIP folder called R files Global Sensitivity Analysis), ten files with the observed and simulated data (Human_In vivo*.xlsx), one file with the Berkeley Madonna code (Supplemental 1*.docx), two files with the parameters (Chemical*.xslx, Parameters*.xlsx), and one file with the GSA results (Global*.pdf). The data allow parameterization, calibration and validation of a generic three-tiered pregnancy PBPK model for 10 drugs and chemicals. The tier 1 model captures compound distribution in the pregnant woman without consideration of the fetus. The tier 2 model includes mathematical descriptions of the placenta and fetal compartment. Finally, Tier 3 models include explicit representations of relevant fetal organ systems. In practice, the utility of Tier 3 PBPK models is constrained by data availability. Models include mathematical descriptions of fetal tissue compartments, but toxicokinetic data for compound concentrations in these compartments are challenging to collect and are, therefore, incredibly rare. The generated dataset can be of interest to toxicologists and regulatory agencies interested in pregnancy modeling.

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