The skin is the main target tissue for exogenous noxae, protecting us from harmful environmental hazards, UV-irradiation and endogenous water loss. Stratum corneum is an effective barrier against a vast number of substances. Furthermore, keratinocytes play crucial roles in the immune surveillance and the initiation, modulation and regulation of inflammation in the epidermis. Regarding cutaneous inflammatory reactions, skin irritation and sensitization are two of the most common adverse effect in humans. Irritant contact dermatitis is the result of an innate inflammatory response of the skin to direct injury caused by a single, repeated or continued application of an irritant, while allergic contact dermatitis is a delayed type of induced sensitivity (allergy) resulting from cutaneous contact with a specific allergen to which the patient has developed a specific sensitivity. For reasons of human safety assessment, new cosmetics are evaluated for irritation and sensitization potentials by application to animals followed by visible changes such as erythema and oedema. Testing for allergic and/or irritant responses in animals potentially causes pain and discomfort. Moreover, the results are not always predictive for those found in humans. Due to ethical and scientific questions and on account of the 7 th amendment of the European Council Directive 76/768/EEC, the authors see the requirement to drive the development of alternative tests for cosmetics. In order to replace animal testing and to improve the prediction of allergic and/or irritant responses, the European Cosmetics Association (COLIPA), is developing and using several alternative in vitro tests. In this respect, the use of in vitro reconstructed organotypic skin equivalents are mostly favoured, because of their increasingly close resemblance to human skin. Therefore, this article centres on cosmetic safety and provides the readership an overview of the state of art of cellular mechanisms of skin irritation and allergy. In vitro irritation models can be divided into 4 categories by identifying an increasing level of complexity: single-cell assay, epidermal equivalent, skin equivalent and excised skin. On the other hand, in vitro sensitization assays range from developing models to predict epidermal bioavailability, investigating how cosmetics are converted within the skin (protein binding, skin metabolism) and characterizing how cosmetics activate skin immune cells (investigating dendritic cells, dendritic cells-like, intracellular signalling pathways, gene and receptor expression changes). Such studies have the potential to identify novel biomarkers and to elucidate the mechanism of irritant and allergic contact dermatitis. Therefore, this article centres on cosmetic safety and provides the readership with an overview of the state of art of cellular mechanisms of skin irritation and allergy and summarizes the results of the most commonly used in vitro assays to evaluate cosmetic safety. © Monte Meru Editrice.
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