103 PRESERVATION OF PERSONAL CARE AND COSMETIC PRODUCTS in recent years, many natural sources have been found (29,58,59). Despite the misguided apprehension about and public fear of preservatives being “bad for you” or “not natural,” parabens have been classified by the United States FDA as GRAS (60). The decreased use of parabens has led, in part, to an increase in the use of isothiazolinones, botanicals, and other newer chemistries that may show higher incidence of allergic response due to their increased use, which is responsible for high medical bills, time away from work and family, and a diminished quality of life (14). The American Contact Dermatitis Society named parabens the “2019 nonallergen of the year” (9). Parabens are some of the least allergenic preservatives available, with rates of contact sensitization between 0.5% and 1.4% – rates that have been stable since the 1990s (61). The CIR Expert Panel has reviewed the safety of parabens several times, most recently in 2019. From the latest results, the panel issued a tentative amended report with the conclusion that 20 ingredients, including MP, ethylparaben, PP, and butylparaben, are safe in cosmetics under the present practices of use and concentrations described in their safety assessments (62). Will COVID-19 encourage consumers to change their mind about parabens? This question is still unanswered, but a deeper understanding of hygiene and contamination brought about by the novel coronavirus disease outbreak may validate their usage (63). PHENOXYETHANOL (PE) AND BENZYL ALCOHOL (BA) Phenols and alcohols are substances with effective antimicrobial properties. Their action is bactericidal, especially with acid-resistant bacilli. At low concentrations, PE and BA may induce membrane lysis in bacteria. Thus, they can denature the structure of proteins by binding to amino acid residues (12). PE has a large spectrum of antimicrobial activity and is effective against various Gram- negative (e.g., P aeruginosa) and Gram-positive (e.g., S aureus) bacteria and against yeasts (e.g., C albicans) (64). According to the Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers—including children of all ages—when used as a preservative in cosmetic products at a maximum concentration of 1% (65,66). According to Grand Review Research, phenol derivates accounted for 35.7% of the total cosmetic preservative market revenue in 2015. In addition, growing demand for PE is expected to spur the highest market growth in this ingredient category: a 6.4% CAGR from 2016 to 2024 (67). PE could be the next “free-from” ingredient because some researchers suggest it could be irritating due to impurities and when tested at 100% concentration, which are not relevant to the levels used in cosmetic products. Recently, safety reviews confirmed that PE is safe at the maximum concentration allowed, a rare sensitizer, and can be considered one of the most well-tolerated preservatives used in cosmetic products (7,64). Nevertheless, with more concerns surrounding product safety, PE and parabens may be better tolerated by consumers. BA is active against Gram-positive bacteria and has some weak activity against Gram- negative bacteria, yeasts, and molds. It is classified as an allergen and frequently causes allergic reactions for example, it has been found to cause allergic reactions in 1.2 to 15% of patients with eczema from cosmetic products (12). In a hazard assessment carried out by

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