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. 

Phenoxyethanol, (Ethylene Glycol phenyl ether (EPH)) ether and aromatic alcohol produced by the reaction of phenol and ethylene oxide under high pressure and at high temperature in the presence of an alkaline catalyst.

The name "Phenoxyethanol" can be decomposed as follows:

• "Phenoxy" indicates the presence of a phenoxy group in the molecule, which is a phenyl ring (a six-carbon aromatic ring) bonded to an oxygen atom.
• "ethanol" indicates the presence of an ethanol group in the molecule, which is an alcohol group (-OH) bonded to a two-carbon chain.

Chemical Industrial Synthesis Process

Phenoxyethanol is synthesized through the reaction of phenol with ethylene oxide in a basic environment. The reaction requires controlled conditions of temperature and pressure, as well as the presence of a basic catalyst such as potassium hydroxide (KOH) or sodium hydroxide (NaOH).

Purification. After synthesis, the crude product may contain impurities such as unreacted phenols and by-products of the reaction. Purification is carried out through techniques like vacuum distillation, which allows for the separation of pure Phenoxyethanol from impurities.

Quality Control. The purified Phenoxyethanol undergoes rigorous quality control checks to ensure its purity, chemical composition, and absence of contaminants. These checks can include analytical methods such as gas chromatography (GC), infrared spectroscopy (IR), and microbiological tests to confirm antimicrobial properties.

 It occurs as a colourless to pale yellow transparent liquid. Mixable with many organic solvents, 783 DBE benzyl alcohol, alcohol, ether, strong permeability.

What it is used for and where it is used

It has been used since 1970 as a broad-spectrum preservative antimicrobial in cosmetics against Gram-negative bacteria, moulds and yeasts. It occurs naturally in green tea but is produced chemically using phenol and ethylene oxide. Germicidal and germicidal, it is often used with a quaternary ammonium compound.

Other applications:

• typical organic solvent with high boiling point and low volatility
• insect repellent 
• excellent solubility for cellulose acetate, inks, resins such as acrylic resins, epoxy resin, alkyd resin, phenoxy resin, ethylcellulose, nitrocellulose, dyes, methyl hydroxybenzoate in the electronic circuit board industry
• perfume fixative
• synthesis of the fungicide propiconazole 
• anaesthetic in fish aquaculture
• UV curing agent
• liquid chromatography transport liquid

Cosmetics

It is a restricted ingredient as V/29 a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Substance or ingredient reported: 2-Phenoxyethanol

Maximum concentration in ready for use preparation:    1.0%

INCI Functions

• Antimicrobial agent. This ingredient is able to suppress or inhibit the growth and replication of a broad spectrum of microorganisms such as bacteria, fungi and viruses by making the stratum corneum temporarily bactericidal and fungicidal.
• Preservative. Any product containing organic, inorganic compounds, water, needs to be preserved from microbial contamination. Preservatives act against the development of harmful microorganisms and against oxidation of the product.

Studies

As for many other preservatives included in the formula of cosmetic products, the scientific literature warns about general and specific contraindications concerning the application of this preservative.

It is considered by ICEA (Institute for Ethical and Environmental Certification) as bio-ecological, but irritating to the skin if higher than 1%.

In general, the 2019 study by B Dréno et al. finds this preservative to be well tolerated and rarely sensitizing. I report its abstract: "Phenoxyethanol, or 2-phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram-negative and Gram-positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers - including children of all ages - when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200-fold higher) than those to which consumers are exposed when using phenoxyethanol-containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well-tolerated preservatives used in cosmetic products." (1).

In contrast, 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." (2).

In a list of the most common 100 allergenic ingredients found in facial creams, cited by Alyssa M Thompson et al (3), Phenoxyethanol ranks second after EDTA and before Cetyl Alcohol.

Phenoxyethanol  studies

Typical optimal characteristics of the commercial product Phenoxyethanol Ethylene Glycol phenyl ether (EPH)

Appearance	Colourless to pale yellow transparent liquid
Assay	≥99.0%
Boiling Point	245.2±0.0 °C at 760 mmHg
Melting Point	11-13 °C
Flash Point	105.3±14.1 °C
pH	5.5-7.0
APHA (Pt-Co	≤30
Water	≤0.2%
Phenol	≤25ppm
PSA	29.46000
LogP	1.16
Vapour density	4.8
Vapour Pressure	0.0±0.5 mmHg at 25°C   0.01 mm Hg ( 20 °C)
Water Solubility	30 g/L (20 ºC)
Index of Refraction	1.526   n20/D 1.539
Auto-ignition temperature	535 °C
Explosion limit	1.4-9.0%(V)
Storage	Room temperature
Safety

• Molecular Formula: C₈H₁₀O₂ or C₆H₅OC₂H₄OH
• Molecular Weight: 138.166 g/mol
• Exact mass   138.068085
• CAS: 122-99-6   9004-78-8
• EC Number: 204-589-7   500-013-6
• UNIII: HIE492ZZ3T
• DSSTox Substance ID 
• InChI=1S/C8H10O2/c9-6-7-10-8-4-2-1-3-5-8/h1-5,9H,6-7H2  
• InChl Key      QCDWFXQBSFUVSP-UHFFFAOYSA-N
• SMILES    C1=CC=C(C=C1)OCCO
• IUPAC   2-phenoxyethanol
• ChEBI  64275
• ICSC    0538
• NSC   1864
• RTECS   KM0350000
• FEMA Number: 4620
• Beilstein Registry Number: 1364011
• MDL number: MFCD00002857
• PubChem Substance ID: 329750804

Synonyms:

• Ethylene glycol monophenyl ether
• Phenyl cellosolve
• Phenoxyethyl alcohol
• Ethanol, 2-phenoxy-
• Phenylmonoglycol ether
• Phenoxytol
• 1-Hydroxy-2-phenoxyethane
• Phenoxethol
• Glycol monophenyl ether
• Phenoxetol
• 2-Hydroxyethyl phenyl ether
• Ethylene glycol phenyl ether

References_______________________________________________________________________

(1) Dréno B, Zuberbier T, Gelmetti C, Gontijo G, Marinovich M. Safety review of phenoxyethanol when used as a preservative in cosmetics. J Eur Acad Dermatol Venereol. 2019 Nov;33 Suppl 7:15-24. doi: 10.1111/jdv.15944.

(2) 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. 

(3) 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. 

Abstract. Ingredients found in facial moisturizers can impact a myriad of skin conditions, including sensitive skin syndrome and contact dermatitis. There is a paucity of evidence on the allergenic potential and marketing claims of facial moisturizers, posing challenges to clinician recommendation and consumer selection. In this study, we systematically evaluate the 100 top-selling sun protective facial moisturizers that claim to be natural, fragrance free, expert-approved, age preventing, beneficial for sensitive skin, and sun protective. Allergenic potential of these moisturizers is evaluated based on ingredients used and prices and consumer ratings are compared. Accordingly, 75 of 100 marketed at least one additional benefit. "Anti-aging" products had the highest average price ($14.99/oz) and "expert-approved" had the lowest ($5.91/oz). Consumer rating was highest for facial moisturizers that were "fragrance-free" (4.35/5.00) whereas products that were "natural" received the lowest ratings (3.49/5.00). The most prevalent allergens found in these moisturizers were ethylenediamine tetraacetic acid (EDTA), phenoxyethanol, and cetyl alcohol. "Expert-approved" products had the fewest average allergens in their ingredient lists (P=0.033), whereas products advertising "SPF" had significantly more (P<0.001). Marketing claims play a role in product sales and ratings. When recommending products, physicians should balance allergenic risk with affordability and consumer preferences.