Phenoxyethanol

Identification

Name
Phenoxyethanol
Accession Number
DB11304
Type
Small Molecule
Groups
Approved
Description

Phenoxyethanol is a colorless liquid with a pleasant odor. It is a glycol ether used as a perfume fixative, insect repellent, antiseptic, solvent, preservative, and also as an anesthetic in fish aquaculture. Phenoxyethanol is an ether alcohol with aromatic properties. It is both naturally found and manufactured synthetically. Demonstrating antimicrobial ability, phenoxyethanol acts as an effective preservative in pharmaceuticals, cosmetics and lubricants [5].

Phenoxyethanol (EU), or PE, is the most commonly used globally-approved preservative in personal care formulations. It is very easy to use in various types of formulations and is chemically stable. Phenoxyethanol is a colorless, clear, oily liquid with a faint aromatic odor at room temperature and a low water solubility and evaporation rate. It is produced by reacting phenol (EU) and ethylene oxide (EU) at a high temperature and pressure. This substance occurs naturally in green tea (EU) [6].

According to the European Union Cosmetics Regulation (EC) n.1223/2009, phenoxyethanol is authorized as a preservative in cosmetic formulations at a maximum concentration of 1.0% [8].

Phenoxyethanol has been classified as an antimicrobial and preservative by Health Canada [7]. It has also been used in vaccines and shown to inactivate bacteria, and several types of yeast [2].

Structure
Thumb
Synonyms
  • 1-Hydroxy-2-phenoxyethane
  • 2-Hydroxyethyl phenyl ether
  • 2-phenoxyethanol
  • 2-Phenoxyethyl alcohol
  • beta-Hydroxyethyl phenyl ether
  • Ethylene glycol monophenyl ether
  • Phenoxytol
  • Phenyl cellosolve
  • Phenylmonoglycol ether
External IDs
FEMA NO. 4620
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Grime Eater Lotion Soap 2.5%Soap2.5 %TopicalGrime Eater Products Ltd.1988-12-312005-06-17Canada
Lanohex Nettoyeur Pour LA Peau 1.7%Liquid1.7 %TopicalRougier Pharma Division Of Ratiopharm Inc1960-12-312003-09-22Canada
Lanohex Shp 1.7%Shampoo1.7 %TopicalRougier Pharma Division Of Ratiopharm Inc1960-12-312000-09-07Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Acropole BleuPhenoxyethanol (.45 %) + Chloroxylenol (.15 %)JellyTopicalParall LtÉe1997-10-012001-07-23Canada
Cosmos HvPhenoxyethanol (.45 %) + Chloroxylenol (.15 %)LiquidTopicalParall LtÉe1996-12-182004-05-25Canada
HydroGold 9Phenoxyethanol (0.5 mg/100mg) + Acetyl hexapeptide-8 (0.01 mg/100mg) + Adenosine (0.04 mg/100mg) + Allantoin (0.2 mg/100mg) + Sodium benzoate (0.5 mg/100mg) + Butylene glycol (2 mg/100mg) + Castor oil (0.4 mg/100mg) + Dimethicone (0.01 mg/100mg) + Glycerin (20 mg/100mg) + Gold (0.0001 mg/100mg) + Nicotinamide (2 mg/100mg) + Potassium Chloride (0.01 mg/100mg) + Titanium dioxide (0.43 mg/100mg) + Xanthan gum (0.5 mg/100mg)PatchTopicalBhmbg Global Branding Inc.2018-03-092019-12-31Us
Manugel 85Phenoxyethanol (0.3 g/500mL) + Ethanol (400 mL/500mL)GelTopicalLaboratoires Anios2014-04-01Not applicableUs
MarcorodexPhenoxyethanol (1 g) + Benzethonium chloride (0.13 g)LiquidTopicalRougier Pharma Division Of Ratiopharm Inc1996-12-102009-08-04Canada
MicroPhenoxyethanol (.45 %) + Chloroxylenol (.15 %)GelTopicalParall LtÉe1997-10-152001-07-23Canada
Categories
UNII
HIE492ZZ3T
CAS number
122-99-6
Weight
Average: 138.166
Monoisotopic: 138.068079562
Chemical Formula
C8H10O2
InChI Key
QCDWFXQBSFUVSP-UHFFFAOYSA-N
InChI
InChI=1S/C8H10O2/c9-6-7-10-8-4-2-1-3-5-8/h1-5,9H,6-7H2
IUPAC Name
2-phenoxyethan-1-ol
SMILES

Pharmacology

Indication

Antimicrobial agent used as a preservative in cosmetics [4], [5], [8].

Pharmacodynamics

This substance has broad-spectrum antimicrobial activity against bacteria, yeasts, and mold [6].

Mechanism of action

Phenoxyethanol has antibacterial properties and is effective against strains of Pseudomonas aeruginosa even in the presence of 20% serum. It not as effective against Proteus vulgaris, other gram-negative organisms, and gram-positive organisms. Phenoxyethanol has been used as a preservative at a concentration of 1%. A wider spectrum of antimicrobial activity is achieved with preservative mixtures of phenoxyethanol and hydroxybenzoates. Phenoxyethanol may be used as a 2.2% solution or a 2% cream for the treatment of superficial wounds, burns, or abscesses infected by Pseudomonas aeruginosa. In skin infection, derivatives of phenoxyethanol are used in combination with either cyclic acid or zinc undecenoate [7].

Absorption
Not Available
Volume of distribution

A pharmacokinetic study of phenoxyethanol was performed using a mass spectrometry model for simultaneous analysis of phenoxyethanol (PE) and its major metabolite, phenoxyacetic acid (PAA), in rat plasma, urine, and 7 different tissues [10].

The absolute topical bioavailability of PE was 75.4% and 76.0% for emulsion and lotion, respectively. Conversion of PE to PAA was extensive, with the average AUCPAA-to-AUCPE ratio being 4.4 and 5.3 for emulsion and lotion, respectively. The steady-state tissue-to-plasma PE concentration ratio (Kp) was higher than unity for kidney, spleen, heart, brain, and testis and was lower (0.6) for lung and liver, while the metabolite Kp ratio was higher than unity for kidney, liver, lung, and testis and was lower (0.3) for other tissues [10].

Protein binding
Not Available
Metabolism

The fate of phenoxyethanol in rats and humans has been investigated [4]. The rate of intestinal absorption was rapid, with 60-70% of the excreted (14)C detected at 3 hours and > 95% of the total 4-day urinary (14)C detected within the first 24 hr. Trace amounts of radioactivity were detected in feces. Four days after dosing, only trace amounts of radioactivity remained in the carcass, primarily in the liver (< 0.2% of the dose), fat and muscle. At the 4 day point, the (14)C concentration in blood was measured to be only 0.001 [4].

The major metabolite of phenoxyethanol is phenoxyacetic acid [10].

Route of elimination

The fate of phenoxyethanol in rats and humans has been investigated. More than 90% of an oral dose of 16, 27 or 160 mg/kg body weight of (2-(14)C)phenoxyethanol administered to male Colworth rats by was excreted in the urine within 24 hours of administration. A female rat also excreted about 90% of a dose of 27 mg/kg body weight in the urine within 24 hours. About 2% and 1.3% of the ingested dose was recovered from the exhaled air of female and male rats, respectively [4].

Half life
Not Available
Clearance
Not Available
Toxicity

LC50 oral, rat; 1980 mg/kg [MSDS]. LD50 Rabbit dermal 2250 mg/kg [4].

2-Phenoxyethanol (PhE) has been shown to induce hepatotoxicity, renal toxicity, and hemolysis at dosages ≥ 400 mg/kg/day in subchronic and chronic studies in multiple species [3].

The major hazards encountered in the use and handling of 2-phenoxyethanol stem from its toxicologic properties. Toxic by all routes (inhalation, ingestion, and dermal contact), exposure to this very faintly aromatic, colorless, oily liquid may occur from its use as a fixative for cosmetics, perfumes, and soaps; as a bactericide and insect repellant; as a solvent for cellulose acetate,dyes, stamp pad, ball point, and specialty inks; as a chemical intermediate for carboxylic acid esters (eg, acrylate, maleate) and polymers (eg, formaldehyde, melamine); and as a preservative for human specimens used for dissection and demonstrations in anatomical studies. Effects resulting from exposure to this substance can include eye irritation, headache, tremors, and central nervous system depression. If contact with the eyes occurs, irrigate exposed eyes with copious amounts of tepid water for at least 15 minutes, and wash exposed skin thoroughly with soap and water. 2-Phenoxyethanol must be preheated before ignition can occur [7].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Morton WE: Occupational phenoxyethanol neurotoxicity: a report of three cases. J Occup Med. 1990 Jan;32(1):42-5. [PubMed:2324842]
  2. Lowe I, Southern J: The antimicrobial activity of phenoxyethanol in vaccines. Lett Appl Microbiol. 1994 Feb;18(2):115-6. [PubMed:7764595]
  3. Troutman JA, Rick DL, Stuard SB, Fisher J, Bartels MJ: Development of a physiologically-based pharmacokinetic model of 2-phenoxyethanol and its metabolite phenoxyacetic acid in rats and humans to address toxicokinetic uncertainty in risk assessment. Regul Toxicol Pharmacol. 2015 Nov;73(2):530-43. doi: 10.1016/j.yrtph.2015.07.012. Epub 2015 Jul 16. [PubMed:26188115]
  4. Phenoxyethanol [Link]
  5. Phenoxyethanol - Brumer [Link]
  6. Phenoxyethanol: A Globally-Approved Preservative [Link]
  7. Health Canada: Phenoxyethanol [Link]
  8. Opinion on Phenoxyethanol - EU Law and Publications [Link]
  9. pharmacokinetic model of 2-phenoxyethanol and its metabolite phenoxyacetic acid in rats and humans to address toxicokinetic uncertainty in risk assessment [Link]
  10. Simultaneous determination of phenoxyethanol and its major metabolite, phenoxyacetic acid, in rat biological matrices by LC–MS/MS with polarity switching: Application to ADME studies [Link]
External Links
Human Metabolome Database
HMDB0041607
PubChem Compound
31236
PubChem Substance
347827964
ChemSpider
13848467
ChEBI
64275
ChEMBL
CHEMBL1229846
HET
268
Wikipedia
Phenoxyethanol
PDB Entries
2rbr
MSDS
Download (37.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
JellyTopical
LiquidTopical
SoapTopical2.5 %
PatchTopical
LiquidTopical1.7 %
ShampooTopical1.7 %
GelTopical
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)13MSDS
boiling point (°C)245MSDS
water solubility24g/L at 20°CMSDS
Predicted Properties
PropertyValueSource
Water Solubility24.1 mg/mLALOGPS
logP1.22ALOGPS
logP1.13ChemAxon
logS-0.76ALOGPS
pKa (Strongest Acidic)15.1ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity38.81 m3·mol-1ChemAxon
Polarizability14.91 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9100000000-b40ca28428e0018311ea
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9100000000-f8c06faa8eb8d23a95c1
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9100000000-7b2a4d4d9b09c7b78741
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9100000000-9bb41b75d1ad646b88f0
GC-MS Spectrum - CI-BGC-MSsplash10-000i-0900000000-9421e4830e44b3388570
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9000000000-f53c3891b4914dd833e8
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9200000000-b5db9ef1d198ca188c7c
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9100000000-ab2d6abdcb42c8020070
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9000000000-480278f55ce8ffc42edb
Mass Spectrum (Electron Ionization)MSsplash10-0006-9100000000-9c2de92b427cc8e30262
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Alkyl aryl ethers / Primary alcohols / Hydrocarbon derivatives
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / Ether / Organic oxygen compound / Hydrocarbon derivative / Primary alcohol / Organooxygen compound / Alcohol
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, primary alcohol, hydroxyether (CHEBI:64275)

Drug created on December 03, 2015 09:52 / Updated on November 02, 2018 07:08