101 PRESERVATION OF PERSONAL CARE AND COSMETIC PRODUCTS Clean beauty is having a moment, with an estimated global growth from US $5.4 billion in 2020 to US $11.6 billion by 2027, growing at a CAGR of 12.07% (13). The U.S. Food and Drug Administration (FDA) and other global institutions have failed to define clean which is sometimes confused with natural, leaving these labels open to interpretation by nondermatologist retailers, bloggers, and celebrities. Clean beauty products often claim to be safe, nontoxic, and has transparent labeling of ingredients. However, clean beauty is not necessarily natural and natural is not necessarily clean. The clean beauty and natural movements have demonized hundreds of compounds, while products with a clean or natural claim are not necessarily safer for consumers (14). Prior to COVID-19, natural consumers avoided ingredients such as preservatives and artificial ingredients in their beauty products due to perceived health risks. With more concern surrounding shelf stability and sanitation across consumer-packaged goods categories, consumers will be more willing to accept these ingredients as long as brands provide evidence of their efficacy and safety from both health and environmental perspectives. As consumers become more aware about viruses and germs living on surfaces, packaging for cosmetic and personal care products may change. Spray and stick formats in both cosmetics and facial skincare have been increasing in popularity, and with the arrival of COVID-19, “touchless” beauty products will see increased demand (15). ANTIMICROBIAL AGENTS BENZALKONIUM CHLORIDE (BAC) Since 1935 a quaternary ammonium compound, BAC, has been used as a preservative in medical preparations, cosmetics, and over the counter products. Benzethonium chloride and cetyl peridium chloride are part of the same chemical group. They act by adsorbing to the cytoplasmic membrane, thus causing leakage of the constituents. They are more active against Gram-positive bacteria. The activity against fungi, mycobacteria, and Gram- negative bacilli is comparatively weak (16,18). BAC is the most common primary active ingredient of non-alcohol-based hand sanitizer (46). The Cosmetic Ingredient Review (CIR) expert panel concluded that BAC may be safely used as an antimicrobial agent at concentrations up to 0.1%. Nevertheless, the panel noted that it might enhance the dermal penetration of other chemicals, thereby increasing the risk of sensitization and/or irritation (47). BENZOIC ACID (BEC) AND SORBIC ACID (SA) AND ITS SALTS Decreased use of traditional preservatives (e.g., parabens, isothiazolinones, formaldehyde releasers, and organic halogens) has boosted interest in alternative means of preservation with other antimicrobial choices, including organic acids such as BEC, SA and its salts (48). BEC and its salt, sodium benzoate (SB), are reported to function as fragrance ingredients, pesticides, pH adjusters, preservatives, and/or viscosity-decreasing agents in cosmetic products (49). In general, BEC and SB have the broadest spectra of antimicrobial activity and are useful against many spoilage bacteria, fungi, and yeasts. As preservatives are used in a wide range of cosmetic product types, they can be applied to the skin, nails, or hair and may come into contact with the eyes and mucous membranes (12,49,50). The

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