Fig. 1

Overall study design to evaluate the potential toxicity of 56 diverse per- and poly-fluoroalkyl substances (PFAS) using human induced pluripotent stem cell (iPSC)-derived cardiomyocytes from multiple donors. Human iPSC-derived cardiomyocytes were from 16 donors and used to test 56 structurally-diverse PFAS in concentration response. Intra- and inter-plate replicates, as well as positive and negative controls, were included to ensure experimental reproducibility. Following exposure to PFAS, functional and cytotoxic phenotypes were evaluated. The concentration-response bioactivity data were used to derive donor-specific phenotypic points of departure (PODs), which were then used to estimate the extent of inter-individual variability and compared to exposure estimates to calculate margins of exposure