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Per- and polyfluoroalkyl substances (PFASs) are widely present in sunscreen products as either active ingredients or impurities. They may penetrate the human skin barrier and then pose potential health risks. Herein, we aimed to develop a physiologically based toxicokinetic (PBTK) model capable of predicting the body loading of PFASs after repeated, long-term dermal application of commercial sunscreens. Ten laboratory-prepared sunscreens, generally falling into two categories of water-in-oil (W/O) and oil-in-water (O/W) sunscreens, were subject to in vitro percutaneous penetration test to assess the impacts of four sunscreen ingredients on PFAS penetration. According to the results, two sunscreen formulas representing W/O and O/W types that mostly enhanced PFAS dermal absorption were then selected for a subsequent 30 day in vivo exposure experiment in mice. PBTK models were successfully established based on the time-dependent PFAS concentrations in mouse tissues (R2= 0.885–0.947) and validated through another 30 day repeated exposure experiment in mice using two commercially available sunscreens containing PFASs (R2= 0.809–0.835). The PBTK model results suggest that applying sunscreen of the same amount on a larger skin area is more conducive to PFAS permeation, thus enhancing the exposure risk. This emphasizes the need for caution in practical sunscreen application scenarios, particularly during the summer months.