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).

106 JOURNAL OF COSMETIC SCIENCE CONTACT DERMATITIS: COMMON FREQUENCY CD is a common skin condition caused by contact with an exogenous agent that elicits an inflammatory response. Acute CD presents as a pruritic, erythematous rash with papules, vesicles, and crusted lesions, while chronic CD is typically associated with secondary skin changes (i.e., lichenification, fissuring, and scaling). The two main types of CD are ICD and ACD. ICD accounts for approximately 80% of CD cases, while ACD is less common (10,75). Since the 1950s, when formaldehyde was found to be the culprit responsible for several outbreaks of dermatitis from textiles and cosmetics, preservatives have been identified as a common cause of CD (76). Some preservatives have long been recognized as important skin sensitizers and are common causes of both occupational and nonoccupational CD. Their impact is due not only to their sensitizing potency (most sensitizing preservatives are strong or extreme sensitizers) but also to their broad source of exposure. The most important preservatives, based on their frequency of use and the prevalence of sensitization, include isothiazolinones, methyldibromo glutaronitrile, iodopropynyl butylcarbamate, formaldehyde, and formaldehyde releasers (61). According to the North American Contact Dermatitis Group, the most common primary geographic sites for CD are the hands, a scattered/generalized distribution pattern, and the face (77). ICD hand lesions involve the palms, the dorsal hand, and the distal dorsal digits but may also involve the interdigital web spaces, where irritants get caught. In contrast, ACD of the hand usually presents as well-demarcated plaques and vesicles involving the dorsal hands, fingers, and wrists. Common allergens include preservatives, fragrances, metals, rubber, and topical antibiotics (78). The North American Contact Dermatitis Group’s study showed that the most frequent specific allergens identified on patch testing in patients with suspected ACD were as follows: of the 10,983 positive allergic reactions, the top 10 most frequent allergens (and their respective prevalence rates) were nickel sulfate (17.5%), methylisothiazolinone (13.4%), fragrance mix I (11.3%), formaldehyde 2% (8.4%), the mixture of methylchloroisothiazolinone and methylisothiazolinone (7.3%), Myroxylon pereirae, Balsam of Peru (7.0%), neomycin (7.0%), bacitracin (6.9%), formaldehyde 1% (6.4%), and p-phenylenediamine (6.4%). The performance of the new allergens in order of frequency was as follows: ammonium persulfate (1.7%), chlorhexidine (0.8%), and hydroquinone (0.3%) (77). ANTIMICROBIAL RESISTANCE Some experts have warned of the link between COVID-19 and antimicrobial resistance (79–81). Several studies have reported outbreaks or an increase in infections with acquisition of multidrug-resistant bacteria during the COVID-19 pandemic (82–86). Increased use of hand sanitizers and other antimicrobial agents and their release in the environment may influence the levels of antimicrobial resistance during the COVID-19 pandemic (80,81,87,88). Antimicrobial agents used in hand sanitizers are also used as preservatives in cosmetic products as quaternary ammonium compounds. Preservatives are used in cosmetics at low concentrations to minimize the risk of toxicity to consumers. However, this small quantity for some chemicals, represents the major factor in the appearance of the resistance phenomenon in microorganisms. In addition, contamination rate, target type, temperature, environmental conditions, and contact