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Orientador: Mary Luci de Souza Queiroz Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: O aumento das reações adversas causadas por conservantes somado a poucas substâncias disponíveis no mercado têm despertado o interesse das indústrias cosméticas no desenvolvimento de novos compostos com ação antimicrobiana. Moléculas derivadas de xilitol, Ésteres de Fosfato de Xilitol e Monoéster de C-8 Xilitol, já tiveram sua atividade contra microrganismos comprovada. Entretanto, além de eficazes, estes compostos devem ser seguros para uso em produtos. Neste trabalho, avaliou-se o perfil toxicológico destas moléculas visando sua aplicação cosmética. Inicialmente, foi realizada avaliação preditiva in silico dos derivados de xilitol para comparação da toxicidade a partir de substâncias conhecidas e utilizadas em produtos. Testes in vitro para avaliação de segurança também foram realizados. Citotoxicidade, fototoxicidade, mutagenicidade e irritação foram os parâmetros estudados para a saúde humana enquanto que se avaliou a biodegradabilidade imediata para saúde ambiental. Adicionalmente, ensaios clínicos de segurança foram realizados para confirmação da tolerância cutânea, da ausência de potencial de sensibilização e da aceitabilidade em condições de uso. Estudos clínicos complementares de eficácia foram feitos para verificar a aplicabilidade dos compostos em formulações cosméticas em relação à melhora de oleosidade, de hidratação, de caspa e ao efeito desodorante. Os resultados obtidos sugerem que as moléculas derivadas de xilitol possuem perfil toxicológico aceitável para formulações cosméticas. Na predição in silico, os compostos apresentaram resultados negativos para mutagenicidade, sensibilização e irritação, baixo potencial de permeação e resultados positivos para biodegradabilidade imediata. Nos estudos in vitro, nossos resultados demonstraram que as moléculas derivadas de xilitol não são fototóxicas ou mutagênicas e são prontamente biodegradáveis. Porém, apresentaram-se irritantes, provavelmente à atividade conservante por serem moléculas biologicamente ativas. Na avaliação clínica de segurança, os compostos derivados de xilitol demonstraram boa tolerância e aceitabilidade com a pele e não são alergênicos. Além disso, estas substâncias também parecem ter a capacidade de auxiliar nos atributos funcionais dos cosméticos. Formulações contendo Monoéster de C-8 Xilitol melhoram a barreira cutânea e mantêm quantidade de água na epiderme e formulações contendo Ésteres de Fosfato de Xilitol apresentaram atividade desodorante e melhoraram a oleosidade da pele. Estes resultados contribuem para o desenvolvimento de compostos conservantes seguros para utilização em produtos para o cuidado da pele Abstract: The increase of adverse effects caused by preservatives together with the lack of available options in the market have arisen cosmetic industries interest in the development of new compounds with antimicrobial action. The effectiveness against microorganisms of Xylitol-derived molecules, Phosphate Xylitol Esters and C-8 Xylitol Monoester, have already been proved. However, these compounds should be safe as well as effective. In this study, the toxicological profile of these molecules was assessed regarding their use in cosmetics. First, in silico analysis was performed in order to compare the toxicity prediction of the xylitol-derivatives chemical structures with known substances that are currently used in products. The safety was also tested in vitro. Cytotoxicity, phototoxicity, mutagenicity and irritation were the chosen parameters to evaluate the substances hazard for human health. Ready biodegradability was performed to assess the impact on the environment. Moreover, safety clinical trials were performed for the confirmation of skin tolerance, absence of sensitization potential and acceptability under conditions of use. Additional clinical studies for efficacy enabled the assessment of the application of the compounds in cosmetic formulations to improve oiliness, moisturization, dandruff condition and deodorant effect. Our results suggested that xylitol-derived molecules have an acceptable toxicological profile considering their use in cosmetics. Regarding the in silico prediction, the compounds presented negative results for mutagenicity, sensitization and irritantion, low permeation potention and positive results for ready biodegradability. In vitro studies results showed that xylitol-derived molecules were not phototoxic or mutagenic and were readily biodegradable. However, they were irritants, probably due to the preservative effect as they are biologically active molecules. In the clinical safety assessment, the compounds presented good skin tolerance and acceptability and they were not allergenic. In addition, these substances also seem to have the capacity of aiding in improving the cosmetic attributes of a formulation. Formulations containing C-8 Xylitol Monoester improved the skin barrier and mantained water amount in the epidermis while formulations containing Phosphate Xylitol Esters presented deodorant activity and improved skin oiliness. These results contribute for the development of safe preservatives for skin care products Doutorado Farmacologia Doutora em Farmacologia

Sensitive skin is a condition characterized by stinging, burning and itching sensations. The diagnosis, pathophysiology and treatment of sensitive skin are still under discussion. In the last years, studies on its epidemiology have been performed, showing a high prevalence and impact on quality of life. Brazilian population was also considered in these studies. Cosmetics, climate changes and skin barrier impairment are the main factors that contribute for skin hyperreactivity. New studies are trying to bring new knowledge about the theme. This review will describe data on epidemiology, triggering factors, pathophysiology, diagnosis and treatment.

In Brazil there is no classification of dermatological products by the presence of vehicles with sensitizing potential. The objective of this study is to create a database to classify such products based on the absence of the selected allergens, aiming at making it available for medical consultation. We conducted an observational study, from the content of labels and/or inserts on the composition of 966 dermatological products in the Brazilian market. No chemical analysis was performed. The database called Programa para Pesquisa de Alérgenos de Contato (www.ppac.com.br) was created, in which safe products for patients allergic to dermatological vehicles are provided.

Children's products are considered safe by the general population and doctors. Labels with terms such as "hypoallergenic" or "dermatologically recommended and tested" denote trust and credibility with the idea that they can be used by any individual. Patients with allergic contact dermatitis may be sensitive to allergens present in any product, including children's. There is insufficient knowledge about allergens in these products in our country. We evaluated 254 children's products, and at least one allergen was present in 236 (93%) of them. The indication of a topical product should be careful and based on contact tests.