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Alternative methods to animal experimentation for the evaluation of photosensitizing potential of UV-filters


Contact allergies are considered complex diseases reaching 15-20 % of the population at least once in lifetime, and the number of cases has increased each day. Some cosmetic ingredients represent higher risk for development of contact allergies, including fragrances, preservatives and hair dyes. Furthermore natural compounds and UV-filters also represent an increasing risk for developing cutaneous allergy. The most commonly used methods to assess skin sensitization still use animal testing, such as LLNA - Local Lymph Node Assay. However, despite some alternative methods to animal testing for the evaluation of skin sensitization are in international validation process, there are no validated in vitro studies that differentiate photosensitizing substances from sensitizing or phototoxic substances. Therefore, the aim of this study is to propose a strategy to evaluate the UV-filters photosensitizing potential by using in vitro assays. For this purpose, firstly the peptide depletion assay (cysteine and lysine), submitted or not to UV radiation, will be employed to predict the photosensitizing potential of different UV-filters. Then, the in vitro assay using dendritic cells exposed to the UV-filters and submitted or not to UV radiation will be performed to analyze the differences in gene expression and intracellular signal transduction profiles of the proposed UV-filters. Subsequently, the substances will be tested using full thickness three-dimensional skin model, submitted or not to UV radiation, to develop a strategy to assess and differentiate the photosensitizing from the phototoxic and sensitizing potential of different UV-filters. For this, studies including cell viability determination, histological analysis, IL-1 alpha, IL-6, IL-8 and IL-18 release, and quantification of the UV-filters photodegradation products will be performed. Different positive and negative phototoxic, photosensitizing and sensitizing controls to differentiate these three categories will be used for the proposed methods. (AU)

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Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020180687638 - Universidade de São Paulo (USP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - September 2018, 14