104 JOURNAL OF COSMETIC SCIENCE Canavez et al. (7), BA was classified as highly eye-irritant and moderate skin-sensitizing. However, the MoS was 148.70, which does not represent a systemic risk, considering the concentrations currently used. Special attention should be considered mainly if the product´s fragrance contains the allergen, which may increase the dose–response relationship. PRESERVATIVE BOOSTERS Each ingredient is added to the cosmetic formulation for a well-defined function, but it can simultaneously contribute to another effect (e.g., antimicrobial activity), thus acting as a multifunctional ingredient. Chelating agents, surfactants, humectants, and phenolic compounds are examples of multifunctional ingredients (12). Preservative boosters are defined as cosmetic ingredients with antimicrobial properties that can significantly reduce (or even replace) the concentration of synthetic preservatives used in cosmetic products and minimize the likelihood of allergic reactions or irritation of the skin. Moreover, preservative boosters can be considered multifunctional ingredients and show not only antimicrobial activity but also other desirable properties useful in cosmetic products (e.g., moisturizing, antioxidant, etc.) (4). Ethylhexylglycerin (EEG) and caprylyl glycol (CG) are recognized for their antimicrobial activity and as boosters of traditional preservatives (i.e., increasing the microbiological spectrum). EEG is used for its surfactant, emollient, mild humectant, perfume solubilization, and antimicrobial properties based on its surfactant-like structure. EEG used at a 0.1% to 0.5% concentration can enhance the antimicrobial activity of synthetic preservatives (e.g., 1,2-pentanediol, phenoxyethanol or MP). CG has moisturizing properties and humectants can influence water activity and consequently preserve cosmetic formulations (4,28,68,69). These ingredients have antimicrobial properties but are not classified as preservatives in Annex V of Regulation No. 1223/2009. An evaluation of the antimicrobial efficacy of CG and EEG was carried out by Lawan et al. (2009). The minimum inhibitory concentration (MIC) of CG for S aureus, P aeruginosa, E coli, and C albicans within 1 d and A niger within 28 d was 0.5%. EEG under the same conditions obtained an MIC of 1.5%. A mixture of CG and EEG at a proportion of 1:3 (0.5%:1.5%) was further prepared at concentrations of 0.5%, 1.0%, 1.5%, and 2.0%. The MIC of the preservative system for S aureus within 3 d, P aeruginosa, E coli, and C albicans within 1 d, and A niger within 28 d was 1.0%. The CIR Expert Panel concluded that EEG and CG are safe in the present practices and concentrations (EEG: 0.000001–8% CG: 0.00003–5%) described in their safety assessments (23,27). Nevertheless, the Expert Panel noted the potential for CG to be a penetration enhancer. Some cosmetic ingredients have been regarded as safe since they do not penetrate the skin. The impact of the penetration-enhancing activity of CG on the safety of other ingredients in formulations should be considered (23). “GREEN PRESERVATIVES”: NATURAL ANTIMICROBIAL AGENTS In recent years, the use of natural ingredients in the cosmetic industry, focusing on sustainability and formulations free of synthetic preservatives, has increased. Recent advances have led to the production of antimicrobial agents obtained via green
105 PRESERVATION OF PERSONAL CARE AND COSMETIC PRODUCTS processes. Natural products (e.g., plant extracts, purified isolates, and essential oils) have been proposed as germ killers in hand sanitizers, soaps, and other cosmetics and body care products (70). These natural substances are often sold in mixtures with CG or EEG (4). Natural compounds comprise the most comprehensively studied group of antimicrobial agents as alternatives to synthetic preservatives (4). The cosmetic industry adapts to the needs of consumers seeking to limit the use of preservatives and to develop preservative- free or self-preserving cosmetics, where preservatives are replaced by raw materials of plant origin (32). However, most of these substances are not recognized as preservatives by cosmetic regulation. Nevertheless, their effectiveness is well established. Several studies have reported the antimicrobial activities of essential oils and plant extracts. The use of 3% Thymus vulgaris essential oil inhibited the growth of S aureus, P aeruginosa, and E coli in formulations O/W and W/O and C albicans only in formulations W/O, but not against A niger (34). The addition of 1 and 2% (v/v) Calamintha officinalis essential oil to O/W cream and shampoo inhibited the growth of the tested bacteria and fungi alone and in mixed culture (71). Lavandula officinalis and Rosmarinus officinalis oils (1.5%) in an O/W cream displayed marked antimicrobial activities against all common test microorganisms (including bacteria and fungi) and environmental isolates (35). The antimicrobial efficiency of 0.9% Calendula officinalis extract was sufficient to preserve the formulation against microorganism contamination (30). The antimicrobial activity of Anacardium occidentale (cashew) leaf extracts at a concentration of 2.5 g (v/v) was shown to be as effective as 0.1% MP in cream formulations (31). Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, along with antioxidant activity. These antimicrobial agents, incorporated into biodegradable poly(anhydride esters) composed of an ethylenediaminetetraacetic acid backbone, have the capability to promote preservation in personal care products (72). Certain consumers have the misunderstanding that raw materials of natural origin are safer than synthetic ones. However, these substances are more complex due to the phytochemical characteristics of their composition and may be unstable in cosmetic formulations, thus generating precursors of product degradation, increasing the potential for dermal sensitization, and/or photosensitization if exposed to UV radiation. These plant-based products also have sensitizing properties and potentially cause ACD. Sensitizing plants in cosmetics include tea tree oil, arnica, chamomile, yarrow, citrus extracts, common ivy, aloe, lavender, peppermint, and others. Case reports of CD and positive patch-test reactions to cucumber, eucalyptus, rosemary, sage, witch hazel, and chamomile have been reported (33,36–38). OVEREXPOSURE OF ANTIMICROBIAL PRESERVATIVES The COVID-19 pandemic has introduced more concerns about the safety of cosmetics and personal care products from a microbiological point of view, though the indiscriminate use of these substances is also not desired. There are preservatives that may cause ACD and ICD (73). Moreover, it is very disturbing that some preservative-resistant bacterial strains isolated from cosmetic products show a degree of cross-resistance with antibiotics (74).
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