Pharmaceutical and cosmetic preparations must be formulated so as to assure elegance of appearance, efficacy of ingredients and a satisfactory shelf life as the product. If the formulation is not self-preserving and if it contains material which could act as a substrate for growth of micro-organisms, the shelf life aspect involves, in addition to several other factors, the choice of a suitable antimicrobial preservative. Such preservatives, when present in the minimum effective concentration, are unfortunately prone to interact with many other materials. A number of papers on the inactivation of preservatives by containers, filters and formulation components have been published. The field has been adequately reviewed by de Navarre (1962), Wedderburn (1964) and, more recently, by Coates (1973). From these reviews and from a study of the literature it became apparent that relatively little work had been done on interactions between preservatives and solid particles in aqueous suspension. Consequently, a range of preservatives not previously investigated in this respect was tested for loss of activity in the presence of fifteen powders commonly used in aqueous suspension in pharmaceutical and cosmetic formulations. In view of the information obtained in this preliminary study and after the development of more satisfactory analytical techniques it was decided to study in greater depth the interaction between these powders and selected organomercurials and quaternary ammonium compounds.

Orientador: Vera Lucia Borges Isaac / Banca: Marcos Antonio Correa / Banca: Gislaine Ricci Leonarodo / Resumo: Cosméticos são usados pelo homem desde a antiguidade e o consumo desse segmento vem aumentando a cada ano, praticamente imune a crises. O Brasil é o quarto maior mercado de cosméticos no mundo, ficando atrás apenas dos Estados Unidos, China e Japão, segundo dados da Associação Brasileira de Higiene Pessoal, Perfumaria e Cosméticos. Dentre as matérias primas que mais causam reações alérgicas estão os conservantes, corantes e composições aromáticas. Assim sendo, a preocupação com a segurança dos conservantes cosméticos deve ser intensificada. Grande importância é dada ao assunto atualmente, existindo a preocupação com o potencial de irritação e toxicidade para o consumidor e não apenas com o aspecto microbiológico. Desta forma, o presente trabalho teve por objetivo avaliar a citotoxicidade e potencial de irritação de conservantes antimicrobianos que são utilizados em cosméticos. Foram realizados ensaios de citotoxicidade, através do método MTT, em células de fibroblastos humano (HDFa), células de queratinócitos humano (HaCaT) e células de carcinoma hepatocelular humano (HepG2) e potencial de irritação em ovos embrionados de galinha através do método HET-CAM. Foram utilizados os conservantes: fenoxietanol, mistura de fenoxietanol e metilisotiazolinona (Fenox/Mit), mistura de metilcloroisotiazolinona e metilisotiazolinona (CMit/Mit), metilparabeno e propilparabeno, que são amplamente utilizados em cosméticos. Os conservantes mais citotóxicos e com maior pontuação de irritação (PI... (Resumo completo, clicar acesso eletrônico abaixo)... / Abstract: Cosmetics have been used by man since antiquity and the consumption of this segment has been increasing every year, practically immune to crises. Brazil is the fourth largest cosmetics market in the world, behind only the United States, China and Japan, according to data from the Brazilian Association of Personal Hygiene, Perfumery and Cosmetics. Among the raw materials that most cause allergic reactions are preservatives, dyes and aromatic compositions. Therefore, concern about the safety of cosmetic preservatives should be intensified. Great importance is given to the subject nowadays, there being concern about the potential for irritation and toxicity to the consumer and not just with the microbiological aspect. Thus, the present work aimed to evaluate the cytotoxicity and irritation potential of antimicrobial preservatives that are used in cosmetics. Cytotoxicity were assessed by MTT assay method using human fibroblast cells (HDFa), human keratinocytes cells (HaCaT) and using human hepatoma cells (HepG2) and irritation potential in embryonated chicken eggs using the HET-CAM method. Preservatives were used: phenoxyethanol, a mixture of phenoxyethanol and methylisothiazolinone (Fenox/Mit), a mixture of methylchloroisothiazolinone and methylisothiazolinone (CMit / Mit), methylparaben and propylparaben, which are widely used in cosmetics. The most cytotoxic and highest irritation score (IS) preservatives considered irritants, were: phenoxyethanol (HaCat IC50: 0,237 mg/mL; HDFa IC50: 0,200 mg/mL; HepG2 IC50: 0,248 mg/mL; IS: 16) and Fenox/Mit (HaCat IC50: 0,156 mg/mL; HDFa IC50: ~0,056 mg/mL; HepG2 IC50: 0,119 mg/mL; IS: 10). The other preservatives, CMit/Mit (HaCat: non-toxic; HDFa: non-toxic; HepG2: >0,0045 mg/mL), propylparaben (HaCat IC50: ~0,200 mg/mL; HDFa IC50: >0,200 mg/mL; HepG2: >0,400 mg/mL)... (Complete abstract click electronic access below) / Mestre