Integrated safety strategy for the development of children’s cosmetic products using in vitro and clinical methodologies

Abstract

Brazil is one of the largest cosmetic markets and represents great opportunities for several beauty niches, including children’s products. Regarding safety assessment and considering the particular needs of the target market, children’s products must be specifically formulated and require special attention to avoid inappropriate use and adverse reactions. Because animal tests are no longer accepted for cosmetic evaluation in Europe, the major challenge in this field is to ensure reliable products using alternative methods and other available data such as those found in the literature. The objective of this study was to define an integrated theoretical and technical rationale for the suitable development of children’s makeup products (lipstick, gloss, blush, and nail polish). Without applying animal methods, formulation safety analyses, toxicological in vitro tests (cytotoxicity, phototoxicity, and skin irritation), and clinical trials were considered. First, a systematic study was performed for selection of the intended ingredients that could be used in each formulation. In vitro methods were applied for the evaluation of cytotoxicity, phototoxicity (following the internationally adopted and validated Organization for Economic Cooperation and Development [OECD] guidance document [GD] OECD GD 129 and test guidelines [TG] OECD TG 432, respectively), and acute skin irritation (using a reconstituted human skin model based on OECD TG 439). Complimentary clinical trials were conducted on adults and children, under pediatrician supervision, for the assessment of skin irritability, sensibility, photoallergy, phototoxicity, and tolerability in real usage conditions. The theoretical components of the rationale for the evaluation of children’s products were based on the following: (1) simple formulations with fewer ingredients in comparison to products for adults; (2) raw materials properly analyzed according to their chemical structures, levels of exposure, and toxicological profiles, including available literature; and (3) fragrances within International Fragrance Association (IFRA) recommendations. Concerning in vitro results, none of the children’s products was identified as phototoxic, as skin irritant, or as significantly cytotoxic in the tested concentrations. Clinical trials also showed negative results for all the toxicological endpoints analyzed, considering adult and children’s panels. The safety rationale developed in the present work, using specific formulation criteria and in vitro alternative methods to animal use, was assertive and well correlated to the results of clinical trials. This rationale represents a practical, integrated, and valuable tool for the development of appropriate formulations and the safety assessment of children’s cosmetic products.