# A Survey of Preservatives Used in Cosmetic Products
## 4 Discussion
The ECHA (European Chemicals Agency) does not classify phenoxyethanol as a sensitizer and regards it as the best-tolerated preservative used in cosmetics [21]. Phenoxyethanol also does not appear to be particularly allergenic: one study found the frequency of allergy to 1% phenoxyethanol to be only 0.24% in patch tests on a group of 6932 patients [22]. Phenoxyethanol (PE), sodium benzoate (SB), and potassium sorbate (PS) were generally classified as safe, based on a local hazard evaluation including skin sensitization and irritation; however, they were classified as highly (PE and PS) and moderately (SB) irritating to the eye and should be used with caution for cosmetic products that may come into contact with this area. Systemic hazard assessment, comprising acute oral toxicity, carcinogenicity, mutagenicity and genotoxicity, and endocrine activity, found all three preservatives to have a low risk; however, PE was found to demonstrate moderate acute oral toxicity [10]. The dermal absorption rating was found to be 100% for each preservative considered here, although this value must have been overestimated. Due to a lack of reliable data, this worst-case scenario needed to be considered for risk assessment purposes [10]. None of the considered preservatives shows any risk of phototoxicity [10]. Extensive in vitro and in vivo tests confirmed that sorbic acid and its salts were not mutagenic, carcinogenic, teratogenic, and clastogenic. The low toxicity of sorbic acid can be explained by its rapid metabolism by similar pathways to other fatty acids. In humans, a few cases of non-immunological contact urticaria and pseudo-allergy have been reported [23]. Sodium benzoate may cause non-immune contact urticaria, with blisters, erythema, and itching. However, the tests were conducted at concentrations higher than those permitted in cosmetic preparations [24]. Benzyl alcohol (BA), whose presence was identified only in our cosmetics survey, may cause high eye irritation and moderate skin sensitization as well as moderate acute oral toxicity [10]. In turn, methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI), ingredients popular in the [PERSON] et al. study, have a high risk of causing skin sensitization, skin and eye irritation, and acute oral toxicity [10; 25]. The skin-irritation potential of phenoxyethanol, the parabens methylparaben and propylparaben, and the formaldehyde releases imidazolidinyl urea and DMDDM hydantoin was evaluated in vivo using the repatch test and repeated open application test (ROAT). Phenoxyethanol and methylparaben showed minor skin irritation potential with a mild erythema reaction, while propylparaben and formaldehyde releases demonstrated high irritancy potential. The results were confirmed by in vitro keratinocyte cytotoxicity assay, which found phenoxyethanol to be the safest among the tested preservatives. The red-blood-cell (RBC) test showed that at the maximum permissible concentrations, all tested preservatives, except propylparaben, had negligible hemolytic impact on RBCs. Propylparaben exhibited considerable damage to the RBC membrane. The HET-CAM assay indicated that the investigated preservatives had a minor irritating effect on blood vessels [26]. The safety of phenoxyethanol was also confirmed in a study by [PERSON] et al., in which the skin of premature newborns was disinfected with a solution of 0.1% octenidine and 2% phenoxyethanol. The solution did not cause serious skin damage in premature infants. Although 2-phenoxyethanol was easily absorbed by the skin, it underwent intensive oxidative metabolism to 2-phenoxyacetic acid [27]. Parabens, esters of para-hydroxybenzoic acid, are widely used in cosmetic, medicinal, and food products. They show high antimicrobial activity against fungi and Gram-positive bacteria and weaker activity against Gram-negative bacteria. Their effectiveness increases as the alkyl chain increases [1; 28]. Parabens are considered _to be one of the least sensitizing preservatives in commercial use_.