Friday, November 6, 2009

2-phenoxyethanol: Neurotoxin, CNS toxin

Also known as ethylene glycol monomethyl ether (EGME).

Note: While this substance was classified by the author as a neurotoxicant and CNS toxicant, it is also linked to reproductive effects in women and men and renal failure/kidney damage. This has not been causally proven by substantive evidence.The developmental effects and neurological damage to fetuses and children and adults is causally proven, however, in addition to the neurotoxic (CNS in particular) effects of the ingredient.

Used as an insect repellent, a topical antiseptic, a solvent for cellulose acetate, dyes, inks and resins, in organic synthesis of plasticizers, in germicides. In vaccines, 2-Phenoxyethanol is an alternative to thiomersal.

Classed as "Very Toxic Material". May lead to kidney, liver, blood and central nervous system (CNS) disorders. Harmful or fatal if swallowed. Effects include behavioural disorders, drowsiness, vomiting, diarrhoea, visual disturbances, thirst, convulsions, cyanosis, and rapid heart rate, CNS stimulation, depression, cardiopulmonary effects, kidney disorders. May also lead to liver and blood disorders. Produces reproductive and developmental effects in experimental animals. May cause reproductive defects. Severe eye and skin irritant. Harmful if swallowed, inhaled or absorbed through the skin. One report describes generalised eczema occurring after vaccination where 2-phenoxyethanol was found to be the sensitising agent., which provides three search options:

Search by manufacturer, which you may not know
Search the database by keying in the chemical ingredient
Search the Chemical Toxicity Database.
Enter phenoxyethanol into the database, and five MSDSs are listed. Enter phenoxyethanol into the Chemical Toxicity Database, and seven entries are listed. A sample of information found on phenoxyethanol includes:
Hazards Identification


Harmful if swallowed
Causes skin irritation
May cause central nervous system depression
May cause kidney damage
May cause respiratory and digestive tract irritation
Target Organs: Kidneys, central nervous system


Skin Contact: Severe irritation or burns
Eye Contact: Severe irritation or burns
Ingestion: May cause gastrointestinal irritation with nausea, vomiting and diarrhoea
May cause central nervous system depression
May cause headache, dizziness, drowsiness, and nausea
Advanced stages may cause collapse, unconsciousness
May cause coma and possible death due to respiratory failure
May cause kidney failure
May be harmful if swallowed
Lesions may appear in the brain, lungs, liver, meninges and heart

Harmful if swallowed, inhaled or absorbed through the skin. May cause reproductive defects.

Studies confirming 2-phenoxyethanol/ethylene glycol monomethyl ether toxicity:

El-Zein R, Albrecht T, Reduction in telomere length in individuals exposed in utero to glycol ether, Arch Environ Occup Health. 2007 Fall;62(3):161-3.

Excerpt: Little is known about the mechanism by which ethylene glycol monomethyl ether (EGME) produces genotoxic effects in humans. The authors found that individuals exposed in utero to EGME showed characteristic dysmorphic features, unexplained mental retardation, and persistent cytogenetic damage.... Findings suggest that exposure to EGME in utero could result in terminal chromosome rearrangements and shortening of telomere length, leading to the observed dysmorphic features and idiopathic mental retardation.

El-Zein RA, Abdel-Rahman SZ, Exposure to ethylene glycol monomethyl ether: clinical and cytogenetic findings, Arch Environ Health. 2002 Jul-Aug;57(4):371-6.

Excerpt: Glycol ethers are known reproductive and developmental toxins in laboratory animals, but little is known about their genotoxic effects in humans. In the current article, the authors tested the hypothesis that human in utero exposure to ethylene glycol monomethyl ether (EGME) is associated with the development of specific congenital anomalies and elevated levels of chromosome aberrations...The study characterizes EGME as a human teratogen, as indicated by the prevalence of characteristic dysmorphic features and persistent cytogenetic damage in individuals exposed in utero to this chemical.

Cecilia Anselmi, Anna Ettorre, In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol, Biochemical Pharmacology Volume 63, Issue 3, 1 February 2002, Pages 437-453

Excerpt: Preservatives are added to many final products, such as detergents, cosmetics, pharmaceuticals and vaccines. We conducted an in vitro investigation of the apoptosis- and necrosis-inducing potential of brief applications (10 min) of four common preservatives: ethylene glycol monophenyl ether, 2-phenoxyethanol (EGPE), imidazolidinyl urea (IMU), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI), and 1,2-pentanediol, a "preservative-non-preservative" best known as pentylene glycol. Externalization of PS, a hallmark of apoptosis, occurred early in HL60 treated with low concentrations of CMI/MI and EGPE and was concomitant with the subdiploid peak in HL60 treated with PG. However, it did not occur in HL60 treated with IMU. In conclusion, at appropriate concentrations, each of the four preservatives modulates the apoptotic machinery by a caspase-dependent mechanism. Thus, apoptosis could be a good parameter to evaluate the cytoxicity of these chemical compounds.

Ulrich Mußhoff, Michael Madeja, Effects of 2-phenoxyethanol on N-methyl-d-aspartate (NMDA) receptor-mediated ion currents, Analytics of Toxicology, Volume 73, Number 1 / March, 1999, pages 55-59

Excerpt: Most of the 17 glycol ethers exerted no effects on the glutamate subreceptors activated by kainate and N-methyl-d-aspartate (NMDA), whereas 2-phenoxyethanol (ethylene glycol monophenyl ether) caused a considerable reduction of NMDA-induced membrane currents in a reversible and concentration-dependent manner. The results indicate a neurotoxic potential for 2-phenoxyethanol.

Johanson G., Toxicity review of ethylene glycol monomethyl ether and its acetate ester, Crit Rev Toxicol. 2000 May;30(3):307-45.

Starek A, Szabla J. [Ethylene glycol alkyl ethers--the substances noxious to health], Med Pr. 2008;59(2):179-85.

Excerpt: Ethylene glycol alkyl ethers (EGAE), 2-methoxyethanol, 2-ethoxyethanol, 2-isopropoxyethanol, and 2-butoxyethanol, are widely used in a variety of industrial and household products. They are found in a number of paints, varnishes, engine fuels, hydraulic fluids, and also in many household products, including floor polishes and glass, leather, and upholstery cleaners. Human and animal studies have shown that EGAE can cause adverse reproductive, developmental, and hematological effects. The oxidation of these chemicals to appropriate aldehydes and alkoxyacetic acids is responsible for their toxic effects. The central nervous system, blood and blood-forming organs, and reproduction are the targets in acute and chronic intoxications with EGAE. Data on exposure, metabolism, biomonitoring, and toxic effects ofEGAE, especially those on hematological disorders in human and laboratory animals are presented in this paper.

Holladay SD, Comment CE, Fetal hematopoietic alterations after maternal exposure to ethylene glycol monomethyl ether: prolymphoid cell targeting, Toxicol Appl Pharmacol. 1994 Nov;129(1):53-60.

Excerpt: Ethylene glycol monomethyl ether (EGME), which is extensively used in the chemical industries, has been associated with hematologic disorders in both humans and experimental animals. EGME is metabolized to the active compound methoxy-acetic acid (MAA), which readily crosses the placenta and impairs fetal development. However, little is known about the effect of maternal EGME exposure on the development of fetal immunity. In the present report, in utero treatment with EGME was found to alter expression of murine thymocyte and liver fetal cell-surface markers. These data suggest that EGME, in addition to producing thymic hypocellularity, may inhibit thymocyte maturation. EGME also reduced the percentage of CD45+ leukocytic cells present in fetal liver, an alteration that appeared to be largely manifested by decreased numbers of CD45R+ and CD44dim prolymphoid cells. In vitro MAA exposure of fetal liver cells enriched for lymphoid precursors resulted in significant inhibition of proliferation. Reconstitution of irradiated hosts with gd 18 fetal liver cells from vehicle and EGME-exposed syngeneic donors demonstrated impaired ability of the EGME-treated fetal liver to repopulate the host spleen with B or T lymphocytes. These data suggest that EGME-induced immunosuppression may result from targeting of multiple hematopoietic compartments. Further, the present data indicate that fetal liver prolymphocytes may represent sensitive targets of EGME exposure.

G. Schmuk, W. Steffens, 2-Phenoxyethanol: a neurotoxicant?, Archives of Toxicology, Volume 74, Numbers 4-5 / July, 2000, pages 281-283

Bagchi G, Waxman DJ., Toxicity of ethylene glycol monomethyl ether: impact on testicular gene expression., Int J Androl. 2008 Apr;31(2):269-74.

Wang W, Chapin RE., Differential gene expression detected by suppression subtractive hybridization in the ethylene glycol monomethyl ether-induced testicular lesion., Toxicol Sci. 2000 Jul;56(1):165-74.

Browning RG, Curry SC. Clinical toxicology of ethylene glycol monoalkyl ethers, Hum Exp Toxicol. 1994 May;13(5):325-35.

Chemical Descriptions:United States National Library of Medicine: PubChem


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