Ethylene Oxide: Uses, Exposure, Toxicity, and Regulation

     I wrote in a recent post that Walter Mugdan, former deputy administrator for EPA’s New York City-based regional office and Superfund director, referred to ethylene oxide as “an incredibly dangerous and carcinogenic chemical that needs to be carefully controlled to protect nearby communities.”

     According to Wikipedia:

“Ethylene oxide is an organic compound with the formula C2H4O. It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly sweet odor.”

“The reactivity that is responsible for many of ethylene oxide's hazards also makes it useful. Although too dangerous for direct household use and generally unfamiliar to consumers, ethylene oxide is used for making many consumer products as well as non-consumer chemicals and intermediates. These products include detergents, thickeners, solvents, plastics, and various organic chemicals such as ethylene glycol, ethanolamines, simple and complex glycols, polyglycol ethers, and other compounds. Although it is a vital raw material with diverse applications, including the manufacture of products like polysorbate 20 and polyethylene glycol (PEG) that are often more effective and less toxic than alternative materials, ethylene oxide itself is a very hazardous substance. At room temperature it is a very flammable, carcinogenic, mutagenic, irritating, and anaesthetic gas.”

     The U.S.  and EU countries are by far the largest producers of EtO, followed distantly by Saudi Arabia, China, and Canada.

     Ethylene Oxide (EtO) is a very important raw material for the production of industrial chemicals. These chemicals are used in many products. Most EtO is used to produce ethylene glycol. Some breakdowns are shown below.

      Global industrial use of ethylene oxide in 2007.

     EtO is widely used as a healthcare sterilant. In the U.S. the EPA regulates EtO via the National Emissions Standards for Hazardous Air Pollutants (NESHAP). They describe it as follows:

“Ethylene oxide (EtO) is a colorless gas used to make other chemicals that are used in making a range of products, including antifreeze, textiles, plastics, detergents and adhesives. EtO also is used to sterilize equipment and plastic devices that cannot be sterilized by steam, such as medical equipment. EtO use can contribute to increased cancer risk. EPA is committed to reducing this risk by taking action to protect communities, workers in commercial sterilization, and others who might be at increased risk from EtO when it is used to sterilize things.”

     While EtO is considered a proven carcinogen by some and a probable carcinogen by others, it also has many other toxic effects. A December 2020 study in the Journal of Toxicology and Environmental Health, Part B, noted that tobacco smoking is the major exposure pathway for EtO. They note that there are both exogenous and endogenous (internal) sources of EtO. We make it in the body in small amounts. A graphic of the different external and internal exposure pathways is shown below.

“…exposure trends in workers have been decreasing over time in the U.S. due to better industry hygiene, engineering controls, and changes in occupational exposure limits. Similarly, tobacco-related exposures to ethylene oxide have also been decreasing over time due to changes in smoking habits in the U.S.”

They note that there are both exogenous and endogenous (internal) sources of EtO. We make it in the body in small amounts. A graphic of the different external and internal exposure pathways is shown below.

     They also note that risks associated with chronic low levels of EtO may be overestimated. Indeed a 2022 article in Chemico-Biological Interactions: Systematic review of the scientific evidence on ethylene oxide as a human carcinogen, states that cancer risks at typical exposures are probably overestimated and that the evidence that EtO is a carcinogen is not clear and consistent. The Union of Concerned Scientists, however, notes that EtO has been shown to be potentially associated with several different kinds of cancer and is mutagenic, which means it changes cell DNA, which would make is especially dangerous to children.

“The maximum content of ethylene oxide in the air according to the US standards (ACGIH) is 1.8 mg/m3 (0.00079 gr/cu ft). NIOSH has determined that the Immediately Dangerous to Life and Health level (IDLH) is 800 ppm.”

It can be smelled between 250 and 700ppm – very close to a possibly lethal dose.

“Ethylene oxide is toxic by inhalation, with a US OSHA permissible exposure limit calculated as a TWA (time weighted average) over 8 hours of 1 ppm, and a short term exposure limit (excursion limit) calculated as a TWA over 15 minutes of 5 ppm.[135] At concentrations in the air about 200 parts per million, ethylene oxide irritates mucous membranes of the nose and throat.”

Accidental poisoning has occurred in healthcare and industrial settings. Chronic exposure at low levels (around 3ppm) has been associated with headaches, nausea, and vomiting.

     A Soviet-era thermobaric bomb used to contain ethylene oxide. However, the updated version, recently used on Ukrainian fighters, uses about 330 pounds of piperylene to create a fuel-air cloud that can kill more people.

“…the ODAB-500P is an improvement on the ODAB-500, a Soviet fuel-air bomb introduced in the 1970s. Inside the ODAB-500, which weighs about 880 pounds, there is nearly 220 pounds of ethylene oxide. However, this basic version of the ammunition is characterized by very low reliability. For this reason, the ODAB-500 was replaced with the newer generation ODAB-500P.”

     The U.S. EPA issued a final rule in April 2024 updating EtO emission standards. However, the new administration’s EPA under Lee Zeldin has indicated that the new standards may be scrapped. Thus far there was an order to reconsider EPA’s upgraded NESHAP standards.

     The Union of Concerned Scientists has an interactive map showing locations for major EtO production facilities in the U.S. and areas the EPA has deemed to have the highest cancer risk.

     The American Chemical Council produced the video below on the uses and management of EtO. 

  

 

References:

 

Ethylene Oxide: New Interactive Map Shows Communities Impacted by Cancer-Causing Chemical. Union of Concerned Scientists. February 7, 2023. Ethylene Oxide: New Interactive Map Shows Communities Impacted by Cancer-Causing Chemical - Union of Concerned Scientists

Systematic review of the scientific evidence on ethylene oxide as a human carcinogen. Heather N. Lynch, Jordan S. Kozal, Anthony J. Russell, William J. Thompson, Haley R. Divis, Rachel D. Freid, Edward J. Calabrese, and Kenneth A. Mundt. Chemico-Biological Interactions. Volume 364, 1 September 2022, 110031. Systematic review of the scientific evidence on ethylene oxide as a human carcinogen - ScienceDirect

Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management. CR Kirman, AA Li, PJ Sheehan, JS Bus, RC Lewis & SM Hays. Pages 1-29 | Published online: 15 Dec 2020. Journal of Toxicology and Environmental Health, Part B Critical Reviews. Volume 24, 2021 - Issue 1. Full article: Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management

Ethylene Oxide: An Essential Chemistry. YouTube. American Chemistry. July 9, 2021. Bing Videos

Ethylene oxide. Wikipedia. Ethylene oxide - Wikipedia

Hazardous Air Pollutants: Ethylene Oxide (EtO). U.S. EPA. Hazardous Air Pollutants: Ethylene Oxide (EtO) | US EPA

Final Rule to Strengthen Standards for Synthetic Organic Chemical Plants and Polymers and Resins Plants. U.S. EPA. Final Rule to Strengthen Standards for Synthetic Organic Chemical Plants and Polymers and Resins Plants | US EPA

Russian precision strike in Belgorod: Ukrainian defenses falter. NGA. Essa News. April 3, 2025. Russian precision strike in Belgorod: Ukrainian defenses falter

Trump EPA Announces Reconsideration of Air Rules Regulating American Energy, Manufacturing, Chemical Sectors (NESHAPs). U.S. EPA. March 12, 2025. Trump EPA Announces Reconsideration of Air Rules Regulating American Energy, Manufacturing, Chemical Sectors (NESHAPs) | US EPA