Ethylene oxide is a chemically-physiological compound, a colourless, flammable gas at room temperature, which is produced industrially by the catalytic oxidation of ethylene. Ethylene is a normal constituent of the human body.

The name defines the structure of the molecule:

• Ethylene is a chemical compound with the formula C2H4, a flammable gas that is commonly used in the production of various chemicals, plastics and solvents. Ethylene is a hydrocarbon and belongs to the alkenes family.
• Oxide refers to a compound that contains an oxygen atom bound to another element. In the case of ethylene oxide, it consists of an oxygen atom bound to one of the carbon atoms in the ethylene molecule.

The synthesis process takes place in several stages:

• Preparation of ethylene. Ethylene is a hydrocarbon that can be obtained from natural gas or petroleum. It is industrially produced by steam cracking, a process in which hydrocarbons are heated to break their chemical bonds and form smaller molecules.
• Oxidation. Ethylene is then oxidized to form ethylene oxide. This is done using a silver catalyst and air or oxygen at high temperatures and high pressure.

What it is used for and where it is used

Ethylene Oxide is a key raw material used in the manufacture of a wide range of chemicals, including antifreeze, textiles, plastics, detergents and resins. It's also used for sterilization of medical equipment and supplies. 

It has antimicrobial, antibacterial and antifungal properties that are used by various industries to sterilise with a relatively long procedure (three to 24 hours). According to the Clean Air Act (United States Environmental Protection Agency) of 1990, ethylene oxide is one of 188 recognised hazardous air pollutants and the use of this gas is strictly regulated as it is considered a human carcinogen. 

Medicine and pharmaceuticals

Ethylene oxide is an intermediate chemical compound in the production of ethylene glycols, glycol ethers, polyethylene glycols, polyethylenes, ethanolamines, ethoxylates, which are used by the plastics industry, the packaging industry and for various types of fibres (glass. polyester). 

It is used for the sterilisation of medical devices that could be damaged if sterilised with steam because they contain electronics or plastic. 

Food

Ethylene oxide is a sterilising smoking agent for spices, dried fruits, dried pulses and others and is also used to improve the ripening of fruits such as tomatoes and bananas.

Cosmetics

It is a restricted ingredient as II/182  a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Carcinogenic 1B Mutagenic 1/B.

Other uses

Ethylene oxide is a losteriliser and carbon dioxide is used as a propellant gas which has replaced Freon or dichlorodifluoromethane (CFC-12) as an environmentally harmful, class I ozone-depleting substance.

It is used in the processing of: paper, leather, coins, scrap metal, bioengineering, laboratories etc.

Safety

Numerous studies have been conducted on the safety of ethylene oxide, and as early as 2012, the IARC (International Agency for Research on Cancer) assessed it as carcinogenic to humans.

In December 2018, the US Environmental Protection Agency (EPA) published an update on the safety assessment, warning that exposure to this chemical can cause, with short-term exposure, depression of the central nervous system and irritation of the eyes and mucous membranes and, with long-term exposure, irritation of the eyes, skin, nose, throat and lungs and damage to the brain and nervous system. The EPA concludes that exposure to ethylene oxide increases the risk of lymphoid cancer and, for females, breast cancer (1).

Ethylene oxide studies

Ethylene Oxide data sheet

Boiling Point	10.7°
Melting Point	−111°C
Flash Point	-17.7ºC
Density	0.882 g/mL at 25 °C(lit.)
LogP	0.01660
Index of Refraction	n20/D 1.3597(lit.)
Safety

• Molecular Formula  C₂H₄O
• Molecular Weight     44.05
• Exact Mass    44.02620
• CAS  75-21-8
• UNII    JJH7GNN18P
• EC Number   200-849-9
• DSSTox Substance ID   DTXSID0020600
• IUPAC  oxirane
• InChI=1S/C2H4O/c1-2-3-1/h1-2H2 
• InChl Key      IAYPIBMASNFSPL-UHFFFAOYSA-N
• SMILES   C1CO1
• MDL number  MFCD00014482
• PubChem Substance ID    329747833
• ChEBI  27561
• ICSC    0155
• Beilstein       102378
• RTECS   KX2450000
• UN   1040
• NCI  C29821
• NACRES  NA22

Synonyms:

• oxirane
• Epoxyethane

References_______________________________________________________________________

(1) ethylene-oxide.pdf (epa.gov) 

Compendium of the most significant studies with reference to properties, intake, effects.

Sheehan PJ, Lewis RC, Kirman CR, Watson HN, Winegar ED, Bus JS. Ethylene Oxide Exposure in U.S. Populations Residing Near Sterilization and Other Industrial Facilities: Context Based on Endogenous and Total Equivalent Concentration Exposures. Int J Environ Res Public Health. 2021 Jan 12;18(2):607. doi: 10.3390/ijerph18020607. 

Abstract. Given ubiquitous human exposure to ethylene oxide (EO), regardless of occupation or geography, the current risk-specific concentrations (RSCs: 0.0001-0.01 ppb) from the U.S. Environmental Protection Agency (EPA) cancer risk assessment for EO are not useful metrics for managing EO exposures to the general U.S. population.

Thier R, Bolt HM. Carcinogenicity and genotoxicity of ethylene oxide: new aspects and recent advances. Crit Rev Toxicol. 2000 Sep;30(5):595-608. doi: 10.1080/10408440008951121.

Abstract. Long-term inhalation studies in rodents have presented unequivocal evidence of experimental carcinogenicity of ethylene oxide, based on the formation of malignant tumors at multiple sites. However, despite a considerable body of epidemiological data only limited evidence has been obtained of its carcinogenicity in humans.

Jinot J, Fritz JM, Vulimiri SV, Keshava N. Carcinogenicity of ethylene oxide: key findings and scientific issues. Toxicol Mech Methods. 2018 Jun;28(5):386-396. doi: 10.1080/15376516.2017.1414343.

Abstract. In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed an evaluation of the inhalation carcinogenicity of ethylene oxide (EtO) in December 2016. This article reviews key findings and scientific issues regarding the carcinogenicity of EtO in EPA's Carcinogenicity Assessment.

Filser JG, Klein D. A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human. Toxicol Lett. 2018 Apr;286:54-79. doi: 10.1016/j.toxlet.2017.07.896.

Abstract. Ethylene (ET) is the largest volume organic chemical. Mammals metabolize the olefin to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates macromolecules and has mutagenic and carcinogenic properties. 

Haufroid V, Merz B, Hofmann A, Tschopp A, Lison D, Hotz P. Exposure to ethylene oxide in hospitals: biological monitoring and influence of glutathione S-transferase and epoxide hydrolase polymorphisms. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):796-802. doi: 10.1158/1055-9965.EPI-06-0915.

Abstract. Ethylene oxide is considered as a human carcinogen. A biomarker of exposure would be a useful instrument to assess the risk in occupationally exposed workers. This cross-sectional study aimed at examining (a) whether the urinary excretion of a metabolite of ethylene oxide, 2-hydroxyethyl mercapturic acid (HEMA), could be used for monitoring occupational exposure and (b) whether glutathione S-transferase (GST) and epoxide hydrolase genotypes influenced biological monitoring.

 Shintani H. Ethylene Oxide Gas Sterilization of Medical Devices. Biocontrol Sci. 2017;22(1):1-16. doi: 10.4265/bio.22.1.

Abstract. Ethylene oxide gas is an agent in the sterilization of medical devices due to its effectiveness and compatibility with most materials. The advantages and disadvantages, as well as its recommended uses, are explored in this review article. 

Kelsey JR. Ethylene oxide derived glycol ethers: A review of the alkyl glycol ethers potential to cause endocrine disruption. Regul Toxicol Pharmacol. 2021 Dec 30;129:105113. doi: 10.1016/j.yrtph.2021.105113.

Abstract. This review systematically evaluates all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors.

McEvoy B, Wiehle SB, Gordon K, Kearns G, Laranjeira P, McLees N. Advancing the Sustainable Use of Ethylene Oxide through Process Validation. Biomed Instrum Technol. 2021 Mar 1;55(s3):35-44. doi: 10.2345/0899-8205-55.s3.35.

Abstract. This article presents relevant experiences and describes challenges and considerations encountered in delivering EO process optimization.

Kirman CR, Li AA, Sheehan PJ, Bus JS, Lewis RC, Hays SM. Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management. J Toxicol Environ Health B Crit Rev. 2021 Jan 2;24(1):1-29. doi: 10.1080/10937404.2020.1852988.

Abstraqct. This review is intended to provide risk assessors and risk managers with a better understanding of issues associated with total exposures of human populations to ethylene oxide from endogenous and exogenous pathways. 

Pohan G, Mattiassi S, Yao Y, Zaw AM, Anderson DEJ, Cutiongco MFA, Hinds MT, Yim EKF. Effect of Ethylene Oxide Sterilization on Polyvinyl Alcohol Hydrogel Compared with Gamma Radiation. Tissue Eng Part A. 2020 Oct;26(19-20):1077-1090. doi: 10.1089/ten.TEA.2020.0002.

Abstract.  This study investigated the effects of terminal sterilization of polyvinyl alcohol (PVA) biomaterials using clinically translatable techniques, specifically ethylene oxide (EtO) and gamma (γ) irradiation. While a few studies have reported the possibility of sterilizing PVA with γ-radiation, the use of EtO sterilization of PVA requires additional study. 

Jain RB. Associations between observed concentrations of ethylene oxide in whole blood and smoking, exposure to environmental tobacco smoke, and cancers including breast cancer: data for US children, adolescents, and adults. Environ Sci Pollut Res Int. 2020 Jun;27(17):20912-20919. doi: 10.1007/s11356-020-08564-z.

Abstract. This study was undertaken to evaluate the associations between concentrations of ETO in whole blood and smoking, exposure to environmental tobacco smoke (ETS), and self-reported diagnosis of cancers including breast cancer.