Sunscreens with Nicotinamide as Skin-Brightening Ingredient Increase Exposure Risk of UV-Filters: Quantitative Analysis of UV-Filter Skin Penetration Based on an Improved <i>In Vivo</i> Confocal Raman Spectroscopy Method

Due to the contradiction between the penetration-promoting function of skin-brightening and the penetration-blocking function of UV-filters in multifunctional sunscreens, the skin permeability and potential health risks of UV-filters in these products have not been fully studied. Therefore, the skin penetration of sunscreens with a skin-brightening function (SBF sunscreens) was investigated using an improved Confocal Raman Spectroscopy (CRS) method. First, a CRS method was developed using Octyl 4-methoxycinnamate and ethylhexyl triazone added in different vehicles as targets. After optimizing spectrum acquisition parameters, an exponential decay function was derived and successfully applied to correct the detection limits of CRS based on a unidirectional diffusion model and Fick's second law. Then, CRS data was validated through Franz diffusion cells <i>in vitro</i>, and results showed a good correlation between CRS data and <i>in vitro</i> data (<i>R</i>² = 0.99), indicating that the developed CRS method can accurately reflect the skin penetration characteristics of UV-filters in different vehicles. A 1.30-2.29 times higher skin uptake level of UV-filters was observed in customized and commercial SBF sunscreens than in traditional sunscreens (with an average amount of 0.81 vs. 0.63 μm/cm² and 1.33 vs. 0.58 μm/cm²), suggesting a higher health risk of chronic use of such sunscreens.