In 2016, the group of European Union experts that monitor consumer safety (SCCS) confirmed the positive judgment on this component, provided it was formulated at a concentration below 1% (1).

Some very important studies, abstracts of which are as follows

Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E. coli (> 5 log reduction of cfu after 30 min), leakage of cellular constituents, disruption of the energy metabolism, morphological deformities of cells and condensation of DNA. Used alone, EHG disrupted the membrane integrity even at low concentrations. In conclusion, sub-lethal concentrations of EHG potentiate the effect of PE through damage of the cell membrane integrity. Thus, adding EHG to PE in a 1:9 ratio has a similar effect on membrane damage and bacterial viability as doubling the concentration of PE. This study provides insight about the mechanism of action of a strong potentiating agent, EHG, which is commonly used in cosmetics together with PE (2).

Phenoxyethanol is a widely used preservative in personal care products. Transient receptor potential vanilloid 1 (TRPV1) on cell membrane is activated by TRPV1 agonist capsaicin resulting in an opening of the channel for calcium influx, which is linked with neurosensory sensations characterized by itching, burning and stinging of skin. Whether uncomfortable skin sensations caused by phenoxyethanol claimed by people having sensitive skin are also due to activation of TRPV1 has not been reported in the literature. OBJECTIVE: The aim of this study was to evaluate whether the TRPV1 is involved in the induction of itching and burning sensation by phenoxyethanol. METHODS AND MATERIALS: The effect of phenoxyethanol on TRPV1 was assessed in vitro on HaCaT cells. The activation of TRPV1 and its inhibition by a TRPV1 antagonist were evaluated by cellular calcium influx. TRPV1 protein expression was also investigated by Western blot. In vivo in a split-face study, phenoxyethanol formulated at 1% was compared to a formulation additionally containing a TRPV1 antagonist. By applying the formulations to the nasolabial fold, the scores of phenoxyethanol-induced sensations were compared to those of the TRPV1 antagonist. RESULTS: In vitro phenoxyethanol induced calcium influx in HaCaT cells in a dose-dependent manner after 20 min. This effect was abolished by a solution containing the TRPV1 antagonist trans-tert-butyl cyclohexanol (ID1609). Phenoxyethanol had no effect on the expression of TRPV1, whereas capsaicin caused a significant downregulation of this receptor in the same experiment. In vivo 1% phenoxyethanol induced a skin burning and itching sensation in a cohort of 60 of 243 Chinese female subjects being sensitive to phenoxyethanol discomfort. The uncomfortable skin sensations were significantly inhibited by ID1609. CONCLUSIONS: Different to capsaicin, phenoxyethanol did not downregulate the expression of TRPV1 in HaCaT cells, suggesting that different regulatory mechanisms may exist for capsaicin and phenoxyethanol. Our experiments demonstrated that phenoxyethanol induces skin misperception and uncomfortable skin sensations like itching and burning comparable to capsaicin via activating TRPV1. The stimulation was inhibited by blocking TRPV1 with ID1609. The present data strengthened hitherto studies that TRPV1 plays a critical role in sensitive skin (3).

Regarding specific glands, this 2020 study by Jingyi Wang et al. warns of the toxicity of Phenoxyethanol to the epithelial cells of the Meibomian gland, which secretes, via its ducts, the human tear film, a major source of lipids. I report the abstract: "Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs." (4).

In a list of the most common 100 allergenic ingredients found in facial creams, cited by Alyssa M Thompson et al (5), Phenoxyethanol ranks second after EDTA and before Cetyl Alcohol.

References_______________________________________

(1) Opinion on Phenoxyethanol - SCCS - 6 October 2016

(2) Langsrud S, Steinhauer K, Lüthje S, Weber K, Goroncy-Bermes P, Holck AL. Ethylhexylglycerin Impairs Membrane Integrity and Enhances the Lethal Effect of Phenoxyethanol. PLoS One. 2016 Oct 26;11(10):e0165228. doi: 10.1371/journal.pone.0165228.

(3) Li DG, Du HY, Gerhard S, Imke M, Liu W. Inhibition of TRPV1 prevented skin irritancy induced by phenoxyethanol. A preliminary in vitro and in vivo study. Int J Cosmet Sci. 2017 Feb;39(1):11-16. doi: 10.1111/ics.12340.

(4) Wang J, Liu Y, Kam WR, Li Y, Sullivan DA. Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells. Exp Eye Res. 2020 Jul;196:108057. doi: 10.1016/j.exer.2020.108057. 

(5) Thompson AM, Kromenacker B, Loh TY, Ludwig CM, Segal R, Shi VY. Allergenic potential, marketing claims, and pricing of facial moisturizers. Dermatol Online J. 2020 Jul 15;26(7):13030/qt5vm144th.