In vitro and in vivo screening for environmentally friendly benzophenone-type UV filters with beneficial tyrosinase inhibition activity

Benzophenones (BPs) are a group of chemically similar organic compounds commonly used in formulations of sunscreen and other personal care products as UV filters to protect our skin against sunlight overexposure. Studies have shown that the occurrence of certain BPs (e.g., BP-3 and its metabolite BP-1) in multiple environmental matrices may increase the incidence of coral planulae bleaching and estrogenic effects on aquatic life. Currently, most BPs are not yet comprehensively screened in vitro and in vivo for their ecotoxicity under environmentally relevant concentrations. This study systematically assessed the in vitro and in vivo toxicity and activity of the 7 most commonly used BPs (BP-1, BP-2, BP-3, BP-4, BP-6, BP-7 and BP-8) to select BP alternatives with lower ecotoxicity and extra beneficial functions. BP-2 (LC₅₀ = 18.43 µM) was least toxic and BP-3 (LC₅₀ = 4.10 µM) and BP-8 (LC₅₀ =1.62 µM) were less and most toxic, respectively, in terms of 96-hr acute mortality of medaka larvae. BP-2 at environmentally relevant concentrations (5–50 nM) did not significantly alter locomotion and oxidative stress responses of medaka larvae from 24-hr to 7-day exposure, whereas BP-3 and BP-8 at 5 nM induced hypoactivity or changed fish swimming angles. Only BP-2 was able to inhibit in vitro mushroom tyrosinase activity, with EC₅₀ value 19.7 µM. Also, BP-2 could effectively suppress melanin formation and tyrosinase activity in zebrafish embryos. Among the 7 tested BPs, BP-2 was the least toxic and the most environmentally friendly UV filter with extra benefit for tyrosinase inhibition and could be a promising alternative to the use of toxic BPs.