Evaluation of Hepatotoxicity in the Human In Vitro HepG2 Model After Exposure to Ten Individual UV Filters, and Six Sunscreen Products After Ex Vivo Pig Skin Permeation

Ultraviolet (UV) filters can cross the skin barrier and enter the body. This in vitro study aimed to assess whether UV filters used in sunscreen products could be hepatotoxic. Human HepG2 liver cells were exposed for 48 h at human relevant concentrations (0.5–100 µM) to ten individual UV filters and transdermal fractions of six commercial sunscreen products. High content analysis was used to assess multiple cell health parameters including cell number, nuclear and mitochondrial parameters and reactive oxygen species. Menadione was used as a cytotoxic positive control that affects all measured parameters. Ranking the individual UV filters by the number of affected markers showed: Menadione > 4-MBC = BP-3 > Avobenzone > Homosalate > Ecamsule = Octinoxate = BP-4 > Amiloxate = EHS = ZnO nanoparticles . After permeation through ex-vivo pig skin in a Franz diffusion cell model, the commercial sunscreen products can be ranked by the number of markers affected as follows: Menadione > Product A = Product C = Product D > Product F > Product E = Product B . The UV filters amiloxate, EHS, ZnO nanoparticles, and sunscreen products E and B did not affect any of the cellular health parameters and thus may be considered the safest with regards to hepatotoxicity. We innovatively combined a model using the HepG2 liver cell line with skin permeation to explore hepatotoxic effects. This approach could be adapted to other organs, such as kidney, endocrine, and reproductive organs, using relevant cell models.