Contribution\nof\nContinued Dermal Exposure of PFAS-Containing\nSunscreens to Internal Exposure: Extrapolation from <i>In Vitro</i> and <i>In Vivo</i> Tests to Physiologically Based Toxicokinetic\nModels

Per-\nand polyfluoroalkyl substances (PFASs) are widely\npresent\nin sunscreen products as either active ingredients or impurities.\nThey may penetrate the human skin barrier and then pose potential\nhealth risks. Herein, we aimed to develop a physiologically based\ntoxicokinetic (PBTK) model capable of predicting the body loading\nof PFASs after repeated, long-term dermal application of commercial\nsunscreens. Ten laboratory-prepared sunscreens, generally falling\ninto two categories of water-in-oil (W/O) and oil-in-water (O/W) sunscreens,\nwere subject to in vitro percutaneous penetration test to assess the\nimpacts of four sunscreen ingredients on PFAS penetration. According\nto the results, two sunscreen formulas representing W/O and O/W types\nthat mostly enhanced PFAS dermal absorption were then selected for\na subsequent 30 day in vivo exposure experiment in mice. PBTK models\nwere successfully established based on the time-dependent PFAS concentrations\nin mouse tissues (<i>R</i><sup>2</sup> = 0.885–0.947)\nand validated through another 30 day repeated exposure experiment\nin mice using two commercially available sunscreens containing PFASs\n(<i>R</i><sup>2</sup> = 0.809–0.835). The PBTK model\nresults suggest that applying sunscreen of the same amount on a larger\nskin area is more conducive to PFAS permeation, thus enhancing the\nexposure risk. This emphasizes the need for caution in practical sunscreen\napplication scenarios, particularly during the summer months.