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

107 PRESERVATION OF PERSONAL CARE AND COSMETIC PRODUCTS time are other factors affecting microbial resistance (12). Preservative resistance may be considered as the inactivation of the preservative agent, the reduction in preservative efficacy, or a tolerance of microorganisms (89). Generally, bacterial endospores (i.e., Bacillus and Clostridium) are the most resistant forms. In contrast, mycobacteria (due to cell wall composition) are more resistant than Gram-negative bacteria, while Gram-positive bacteria are most sensitive to preservatives (19). Microbiological contamination of cosmetic products is a matter of great importance to the industry and is potentially a major cause of both product and economic losses. The most common signs of microbial contamination are organoleptic alterations, (e.g., offensive odors), changes in viscosity, and color alterations (74). Moreover, in some cases, exposure to pathogenic microorganisms may cause human health problems (e.g., skin irritation, ACD, and infection, especially in the eyes, mouth, or wounds) (90,91). The different types of microorganisms vary in their response to antimicrobial agents and have different cellular structures, compositions, and physiologies. Traditionally, microbial susceptibility to antimicrobials has been classified based on these differences (92). The resistance of different types of bacteria (mycobacteria, nonsporulating bacteria, and bacterial spores) can be either a natural property of an organism (intrinsic) or acquired by mutation or acquisition of plasmids (self-replicating, extrachromosomal DNA) or transposons (chromosomal or plasmid integrating, transmissible DNA cassettes). Intrinsic resistance is demonstrated by Gram-negative bacteria, bacterial spores, mycobacteria, and, under certain conditions, staphylococci. Acquired, plasmid-mediated resistance is most widely associated with mercury compounds and other metallic salts. In recent years, acquired resistance to certain other types of biocides has been observed, notably in staphylococci (92,93). In comparison with bacteria, little is known about the ways in which fungi can circumvent the action of antimicrobial agents (94). There are two general mechanisms of resistance: (1) intrinsic resistance, a natural property or development of an organism, in which the cell wall presents a barrier to reduce or exclude the entry of an antimicrobial agent and (2) acquired resistance (95). Mold spores, although more resistant than nonsporulating bacteria, are less resistant than bacterial spores to antiseptics and disinfectants. The cell wall composition in molds may confer a high level of intrinsic resistance on these organisms (92). Some examples of mechanisms of microorganism resistance are organic acids (e.g., BEC), sorbic acid and its salts, which can be related to (1) degradation of the organic acid, sorbic acid may be degraded to 1,3-pentadiene by some species of Penicillium, and BEC is metabolized by several species of Pseudomonas and by Acinetobacter calcoaceticus (96) and (2) adaptation of the microorganisms to the acidic medium (the yeasts only adapt to small- chain fatty acids) may be achieved by using the H+-ATPase pump, by the accumulation of the anions to buffer acid pH, or by the synthesis of acid shock proteins (20). In the case of parabens, microorganisms are resistant due to (1) enzymatic inactivation after hydrolysis to 4-hydroxybenzoic acid by esterase (2) super expression of efflux pump genes and possibly (3) porin deficiency (97–99). The external membrane and lipopolysaccharides of Gram-negative bacteria can be responsible for the high intrinsic resistance to quaternary ammonium compounds (e.g., BAC). Pseudomonas aeruginosa modifies the outer membrane structure by changing its fatty acid composition and phospholipids, hindering the penetration of such antimicrobials (19,100). Microorganisms are very versatile and adaptive and, to survive, they need to be capable of dealing with toxic substances. There are multiple components in microbial cells that