Raw in vitro screening data and R scripts for: A Bayesian method for population-wide cardiotoxicity hazard and risk characterization using an in vitro human model

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes are an established model for testing potential chemical hazards. Inter-individual variability in toxicodynamic sensitivity has also been demonstrated in vitro; however, quantitative characterization of the population-wide variability has not been fully explored. We sought to develop a method to address this gap by combining a population-based iPSC-derived cardiomyocyte model with Bayesian concentration-response modeling. A total of 136 compounds, including 44 pharmaceuticals and 82 environmental chemicals, were tested in iPSC-derived cardiomyocytes from 43 non-diseased humans. Hierarchical Bayesian population concentration-response modeling was conducted for five phenotypes reflecting cardiomyocyte function or viability. Toxicodynamic variability was quantified through the derivation of chemical- and phenotype-specific variability factors (TDVF). Toxicokinetic modeling was used for probabilistic in vitro-to-in vivo extrap...