IngredientsImportant Editorial Note: Comprehensive searches of peer-reviewed literature, government health databases (NIH, NIOSH/CDC, OSHA, EPA, ECHA/EFSA, WHO), pharmacopeias, and evidence databases including PubMed/MEDLINE return no evidence whatsoever that 2-ethoxyethanol is, or has ever been classified as, a dietary supplement, nutraceutical, botanical ingredient, or natural health product. It does not appear in any dietary supplement monograph (WHO, ESCOP, German Commission E, USP dietary supplement compendium, or European Pharmacopoeia supplement sections). The term "ethoxyethanol" in all authoritative sources refers exclusively to a synthetic industrial solvent subject to strict occupational hazard regulation due to well-documented toxicity to the reproductive system, blood-forming tissues, and developing fetuses. The following article reflects what the authoritative scientific and regulatory record actually contains about this substance.
The IUPAC name of the compound is 2-ethoxyethanol; its CAS name is "Ethanol, 2-ethoxy-"; its EC number is 203-804-1; its CAS number is 110-80-5; its molecular formula is C₄H₁₀O₂; and its molecular weight is 90.1 g/mol. Recognized synonyms include ethylene glycol monoethyl ether (EGEE). Further synonyms in common use include glycol ethyl ether, cellosolve, glycol monoethyl ether, ethoxyethanol, ethylene glycol ethyl ether, glycol ether EE, and ethyl cellosolve.
2-Ethoxyethanol is a stable, colorless, flammable liquid, synthetically produced throughout the world. It belongs to a larger group of glycol ether solvents. 2-Ethoxyethanol is commercially referred to as Ethyl Cellosolve or Cellosolve, a trademark registered by Union Carbide in 1924. This chemical is a clear, colorless liquid bearing a mild, sweet odor, and is notably miscible with water, alcohols, and ethers, thereby highlighting its role as a versatile solvent in industrial applications.
Its molecular structure consists of an ethanol backbone where an ethoxy group replaces one hydrogen atom, which significantly alters its physical and chemical properties compared to its parent compounds. It was first synthesized to have the same chemical properties of both alcohols and ethers (hydrophilic and lipophilic) but less volatile, which improves production characteristics. The glycol ethers are made by reacting anhydrous alcohols with ethylene oxide.
It is miscible in all proportions of acetone, benzene, carbon tetrachloride, ethyl ether, methanol, and water.
2-Ethoxyethanol has no natural botanical or biological source. It is produced by the reaction of ethylene oxide with ethanol. It is entirely a synthetic compound. There is no peer-reviewed or regulatory documentation identifying 2-ethoxyethanol as occurring naturally in any plant, food, or biological organism intended for human consumption.
This compound is listed in the SVHC (Substances of Very High Concern) candidate list of ECHA (European Chemicals Agency). It was identified as toxic to reproduction (classified in reproductive toxicity categories 1A or 1B) in the EU harmonised classification and labelling and/or by a REACH registration dossier.
No traditional medicinal, dietary, or ethnobotanical use of 2-ethoxyethanol has been documented in any culture or historical period in the peer-reviewed literature, WHO traditional medicine databases, or official pharmacopeial monographs. The compound did not exist prior to its industrial synthesis in the early twentieth century.
The name Cellosolve was registered in 1924 as a United States trademark by Carbide & Carbon Chemicals Corporation (a division of Union Carbide Corporation) for "Solvents for Gums, Resins, Cellulose Esters, and the Like." Its history is entirely one of industrial chemical manufacturing and use, not of medicinal or dietary application.
The Toxic Substances Control Act (TSCA) Inventory for 1977 reports a wide range of production volumes for 2-ethoxyethanol, as many as 171 million pounds. Both 2-methoxyethanol and 2-ethoxyethanol are used as solvents in the manufacture of protective coatings such as lacquers, metal coatings, baking enamels, phenolic varnishes, epoxy resin coatings, and alkyd resins. They are also used as solvents for nitrocellulose, printing inks, textile dyes and pigments, and leather finishes.
2-Ethoxyethanol was once used in cosmetic products but is no longer used due to toxicity associated with dermal absorption. Global production has been on the decline in recent years based on demonstrated toxicity through oral, dermal, and inhalation routes of exposure. The use of ethylene glycol ethers has largely been replaced by relatively safer substitutes, primarily propylene glycol ethers; however, their use as a solvent and chemical process intermediate poses potential for release into the environment.
2-Ethoxyethanol is widely used as an industrial solvent and production intermediate. The glycol ethers are miscible in polar and nonpolar solutions, which make them useful solvents in paints and surface coatings, stains, lacquers, inks, and dyes. Ethylene glycol monoethyl ether is also used in varnish removers, lacquers, and as a solvent for printing inks, duplicating fluids, and epoxy. Additional uses include industrial deicing, hydraulic fluids, and cleaning agents.
It, like other glycol ethers, is used in the semiconductor industry. It is also used in surface coatings such as lacquers and paints. Due to the vast use of glycol ethers there are multiple occupations where exposure occurs, for example, painters, printers (silk-screen, offset, and stamping printers), cleaning workers, graffiti removers, textile and dyeing industry workers, and workers handling fuel.
In research environments, 2-ethoxyethanol is primarily utilized for its solvent properties, particularly in the formulation of inks, dyes, and stains. It efficiently dissolves both polar and non-polar substances, making it invaluable in the synthesis and application of various chemical products.
2-Ethoxyethanol (molecular formula C₄H₁₀O₂; CAS 110-80-5) is itself a single, pure synthetic chemical and does not contain constituent phytochemicals as botanical ingredients do. Its biological significance — and toxicological profile — is driven primarily by its metabolic transformation after absorption.
2-Ethoxyethanol is readily absorbed through the skin, lungs, and gastrointestinal tract. Once absorbed, it is rapidly metabolized. The metabolic pathway involves dehydroxylation by alcohol dehydrogenase. The resulting aldehyde is quickly reduced to form ethoxyacetic acid, the primary metabolite. Further conjugation occurs in rodents to form the secondary metabolite, ethoxyacetyl glycine; however, the glycine conjugate has not been observed in humans.
Ethoxyacetic acid is detected in blood and mucous membranes within minutes. Addition of ethanol will slow the process as a result of competitive inhibition of alcohol dehydrogenase. Finally, the ethoxyacetic acid is dealkylated by P450 monooxygenase and eliminated.
The routes of ¹⁴C excretion following the administration of a single oral 230 mg/kg body weight dose of 2-ethoxyethanol to male Sprague-Dawley rats were investigated. Elimination of the ¹⁴C by the urinary route accounted for 76 to 80% of the dose within 96 hours. The main pathway of biotransformation is oxidation to the corresponding acid, with some subsequent conjugation of the acid metabolite with glycine. The major metabolites, ethoxyacetic acid and N-ethoxyacetyl glycine, representing 73 to 76% of the administered dose, were eliminated in the urine.
The toxicity associated with 2-ethoxyethanol is likely caused more by the primary metabolite, ethoxyacetic acid, than by the parent compound. The metabolites have a longer half-life, implying higher accumulation following repeated exposures. Both in vitro and in vivo studies have shown toxic effects from administration of the metabolites that were not seen at higher doses of the parent.
These glycol ethers have in common metabolic pathways which can lead to significant production of ethoxyacetic acid. Experimental data have shown that this metabolite is responsible for the reproductive toxicity observed.
After administration of the ethanol-labeled compound in rats, the only radiolabeled component found in the rat testes was identified as ethoxyacetic acid. Results of this study suggest that the reported testicular effects in the rat may be a result of tissue levels of ethoxyacetic acid.
Editorial note: All documented scientific evidence concerns toxicological harm, not therapeutic or health-promoting effects. No peer-reviewed evidence supports any beneficial health use of 2-ethoxyethanol in humans or animals.
Developmental and male reproductive toxicity has been widely documented for several compounds in the glycol ether family, and potency is associated with the length of the hydrocarbon chain: the shorter the chain, the more potent the developmental and reproductive effects.
Toxic effects of 2-ethoxyethanol in rodents include teratogenicity, fetotoxicity, hematotoxicity, and testicular atrophy.
In terms of mechanism, despite the vast collection of toxicity studies conducted internationally, the exact mechanism of developmental and reproductive toxicity is not well understood. A potential mechanism for the male reproductive toxicity is direct action on Sertoli and/or germ cells by ethoxyacetic acid.
In animal studies, sperm count and percent normal morphology were decreased at weeks 5 and 6, and sperm motility was decreased at week 6. These data, along with other studies, indicated that the pachytene spermatocyte was the most sensitive target for 2-ethoxyethanol. In vitro studies monitored O₂ consumption and ATP concentrations in isolated pachytene spermatocytes treated with 10 mM 2-ethoxyethanol or 1 or 10 mM ethoxyacetic acid (EAA), the reported active metabolite of 2-ethoxyethanol. A decrease in ATP concentration was seen only with 10 mM EAA. These results indicated that EAA interfered with energy metabolism in the pachytene spermatocyte. This effect may, in part, explain the testicular toxicity produced by this compound.
Investigators have found that ethoxyacetic acid can cause degeneration of spermatocytes in vitro, and damage to spermatocytes seen in vivo can be suppressed when metabolism of 2-ethoxyethanol is inhibited.
To evaluate whether long-term exposure to 2-ethoxyethanol may affect semen quality, a cross-sectional study was conducted among men exposed to 2-ethoxyethanol used as a binder slurry in a metal castings process. Full-shift breathing-zone exposures to 2-ethoxyethanol ranged from non-detectable to 24 ppm (geometric mean 6.6 ppm).
The average sperm count per ejaculate among the workers exposed to 2-ethoxyethanol was significantly lower than that of the unexposed group (113 versus 154 million sperm per ejaculate respectively; p = 0.05) after consideration of abstinence, sample age, subjects' age, tobacco, alcohol and caffeine use, urogenital disorders, fever, and other illnesses. No effect of exposure on semen volume, sperm viability, motility, velocity, and normal morphology or testicular volume was detected.
The study authors concluded that there is a possible effect of 2-ethoxyethanol exposure on sperm count among these workers, but other factors may be affecting semen quality of both exposed and unexposed workers. The cross-sectional design and low participation rate (50% of exposed workers) limit causal inference from this study.
In manufacturing workers, exposure to ethylene glycol ethers has been related to an increased risk of miscarriage, birth defects, reduced fertility and prolonged menstrual cycles. In particular, exposure to 2-methoxyethanol and 2-ethoxyethanol has been associated with reduced semen quality in shipyard painters, metal casters, chemical industry workers and workers in the semiconductor industries.
Previously used glycol ethers (2-alkoxyethanols, mainly 2-methoxyethanol and 2-ethoxyethanol) were found to cause multiple adverse health effects, including hematological effects, oligospermia and azoospermia, reproductive problems, and immunotoxic effects, therefore they have been substituted with less hazardous solvents with redesigned chemical structures.
The experimental studies in animals clearly demonstrate that 2-ethoxyethanol induces adverse reproductive, developmental and hematological effects. Several species (e.g., rats, rabbits and mice) exposed through several routes of exposure (e.g., oral, dermal, and inhalation) have consistently shown these effects.
2-Ethoxyethanol has been shown to be a teratogen in animal studies, and is a possible human teratogen.
The developmental studies available demonstrate that 2-ethoxyethanol is a dermal teratogen and that a developmental LOAEL of 93 mg/kg/day can be established for the chemical.
In zebrafish embryotoxicity testing, methoxyacetic acid and ethoxyacetic acid appeared as the most potent glycol ether metabolites, inducing growth retardation and malformations. Other glycol ethers showed no developmental toxicity.
In a National Toxicology Program study, 2-ethoxyethanol (purity 99%) was administered in deionized drinking water to thirty 6-week-old male F344/N rats per dose for 60 days. Animals were treated with doses of 0, 5,000, 10,000, or 20,000 ppm in drinking water available ad libitum. The study authors reported average daily doses of 0, 407, 792, or 2,390 mg/kg-day.
Examinations of male and female workers exposed to ethoxyethanol reveal hematopoietic effects manifested as anemia and alterations in numbers of white blood cells. Exposures were estimated as at, or below, 1 ppm.
A 2017 human study at a screen-printing facility found measurable hematological effects. Thirty-four screen-printing workers who were exposed to 2-butoxyethanol and 2-ethoxyethanol and 37 non-exposed clerical workers were selected. The chi-square test showed the reticulocyte percentages and corrected reticulocyte counts to be significantly higher in the exposed group. The t-tests showed a significant increase in white blood cell counts, reticulocyte percentages, and corrected reticulocyte count in the exposed group, with p-values of 0.002, 0.004, and 0.002, respectively. Multivariate analysis showed the odds ratio for the corrected reticulocyte counts to be 16.30 for the exposed group compared with that of the control group.
In animals, 2-ethoxyethanol produces irritation of the eyes and respiratory system; blood changes; and liver, kidney, and lung damage, as well as reproductive and teratogenic effects. Long-term effects from exposure to 2-ethoxyethanol are possible kidney damage, damaged blood cells, damaged testes in males, and decreased fertility in males.
Short-term exposures to 2-ethoxyethanol may irritate the eyes, nose, and throat. Very high levels may cause dizziness, lightheadedness, and loss of consciousness.
The following figures are derived exclusively from occupational exposure and toxicological research. They are presented for scientific context only, not as recommended human intake levels:
2-Ethoxyethanol is classified under the EU's CLP Regulation (Regulation EC No 1272/2008) and is indexed in the SVHC Candidate List under the REACH Regulation. It meets the criteria for classification as toxic for reproduction under Regulation 1272/2008/EC. Employment restrictions under the EU Maternity Protection Directive (92/85/EEC) apply for expectant or nursing mothers.
The National Institute for Occupational Safety and Health (NIOSH) recommends that 2-ethoxyethanol be regarded in the workplace as having the potential to cause adverse reproductive effects in male and female workers. NIOSH also recommended that dermal contact to 2-ethoxyethanol and its acetates be prohibited.
The Occupational Safety and Health Administration (OSHA) proposed to amend its existing regulation for occupational exposure to 2-ethoxyethanol and its acetates ("Glycol Ethers") contained in 29 CFR 1910.1000 Table Z-1.
2-Ethoxyethanol is readily absorbed through the skin, lungs, and gastrointestinal tract. The compound's ability to penetrate intact skin is a particular concern: because of the potential for substantial absorption of 2-ethoxyethanol through skin, urine measurements of the metabolite 2-ethoxyacetic acid were conducted as a biomonitoring approach in occupational studies, showing levels ranging from non-detectable to 163 mg 2EAA/g creatinine.
Addition of ethanol will slow the metabolic activation of 2-ethoxyethanol as a result of competitive inhibition of alcohol dehydrogenase. More than light alcohol consumption can cause liver damage. Drinking alcohol may increase the liver damage caused by 2-ethoxyethanol.
In the late 1970s, many studies began to be published regarding adverse effects, including testicular atrophy, infertility, fetotoxicity, and fetal malformations in laboratory animals exposed to glycol ethers. This body of evidence drove regulatory action and industrial substitution. Global production has been on the decline in recent years based on demonstrated toxicity through oral, dermal, and inhalation routes of exposure. The use of ethylene glycol ethers has largely been replaced by relatively safer substitutes, primarily propylene glycol ethers.
2-Ethoxyethanol is a synthetic industrial solvent with no documented use as a dietary supplement, nutraceutical, food ingredient (beyond trace flavor-adjacent esters discussed in early patents), or natural health product. All authoritative bodies — NIOSH, OSHA, ECHA, EPA — classify it as a reproductive and developmental hazard. The scientific literature is consistent in showing, across multiple animal species and multiple routes of exposure, that 2-ethoxyethanol and its primary metabolite ethoxyacetic acid cause testicular toxicity, sperm count reduction, embryotoxicity, teratogenicity, hematotoxicity, and organ damage. Limited human epidemiological data from occupationally exposed workers are directionally consistent with animal findings. There is no evidence base for any beneficial health effect from intentional human exposure to this compound.
Health conditions that Ethoxyethanol may help support.
Body systems that Ethoxyethanol may help support.
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