102 JOURNAL OF COSMETIC SCIENCE Scientific Committee on Consumer Products ensures that BEC and SB are safe for use for preservative purposes in cosmetic rinse-off and leave-on products at the current maximum concentrations allowed (49,51). SA and its salt, potassium sorbate (PS), have broad spectrum of fungistatic activity but are less active against bacteria. Their antimicrobial activity depends upon the amount of undissociated acid, which is determined primarily by the dissociation constant (1.73 × 105 for sorbic acid) and the pH of the system (up to 6.5). While sorbic acid occurs naturally in some berries, virtually all the world’s supply of sorbic acid (which PS is derived) is manufactured synthetically (50,52). PS and SB are listed among compounds that are generally regarded as safe (GRAS) by the United States FDA (50). PS and SB were classified as safe (Margin of Safety: 619.58 and 743.50, respectively) according to Canavez et al. (7) but should be used with caution for cosmetic products that may come into contact with the eyes, as they were classified as highly and moderately irritating to the eye, respectively, in hazard assessments. CHLOROXYLENOL (CX) CX is a commonly used preservative agent in cosmetics or as an antimicrobial agent in personal care products. The mechanism of action of CX is commonly assumed to be similar to those of other phenol and halophenol antimicrobials, specifically perturbing membranes and causing cell leakage. CX is bactericidal, good at killing Gram-positive bacteria, but less active against P aeruginosa (18,24). With the recent ban of triclosan and triclocarban from some personal care products (53,54), many replacements antimicrobial compounds have been used. Nonetheless, the potential health risk and environmental impacts of these replacement compounds are largely unknown. The commonly used replacement antimicrobials are BAC, benzethonium chloride, and CX (55). CHLORPHENESIN (CP) CP functions as a biocide in cosmetics. Reportedly, CP has bactericidal activity against Gram-positive and Gram-negative bacteria as well as fungicidal activity against Aspergillus niger and Penicillium pinophilum (fungi) and is also active against C albicans and Saccharomyces cerevisiae (yeasts). It is used in hair, foot, and suntan sprays and could possibly be inhaled (56). CP is considered safe in the present practices of use and concentration (56). The margin of safety (MoS) value calculated by Canavez et al. (7) in exposure assessment was 123.92, and a similar MoS value (120.00) was also calculated by the Scientific Committee on Cosmetology, which does not represent a systemic risk in normal conditions of use (57). PARABENS Parabens are esters of p-hydroxybenzoic acid, which are widely used as broad-spectrum antimicrobial preservatives (particularly against molds and yeast) in cosmetics, beverages, foods, and pharmaceuticals for more than 70 y. Methylparaben (MP) and propylparaben (PP) are by far the most used (9). Generally, they are considered synthetic compounds, but

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