j EO pardy!
Recently, ethylene oxide (EO or EtO) has been having its moment in the national media spotlight. Perhaps the last time it featured so prominently was during the buzz generated back in the 1940s. At the time, EO was discovered to be a powerful insecticide, fungicide and sterilization agent, and was adopted by the U.S. Army to fumigate rations and prevent transmission of food-borne illnesses to the troops fighting in World War II. To this day, it is used to sterilize certain perishable commodities such as spices, dried herbs, sesame seeds, and walnuts, along with a host of other important contemporary uses.
EO, a colorless gaseous compound at room temperature, is produced by chemical manufacturers in large volumes (2.9 million metric tons/year in the U.S.) as a key precursor for a variety of products such as antifreeze, detergents, adhesives, plastics, and textiles. It is also used extensively to sterilize medical devices and equipment and has a unique ability to penetrate plastic and packaging and safely sterilize sensitive equipment without damage that could be caused by steam or radiation sterilization methods. According to the U.S Food and Drug Administration, EO is currently used to treat an estimated 50 percent of all sterile medical devices in the U.S. – about 20 billion medical devices each year. So, if you’ve had a medical or dental procedure since the 1940s, chances are EO was used to sterilize at least some of the products used by your doctor or dentist. It would not be an exaggeration to say that EO has, in some way or another, impacted each of our everyday lives.
Unfortunately, one of the qualities that makes EO so useful as a sterilant and chemical precursor – its high reactivity due to a strained ring configuration – also results in properties that pose long-term health risks to humans. In 1984, The US Occupational Health and Safety Administration (OSHA) set permissible exposure limits for workers of 1 part per million (ppm) of EO in air over an 8-hour period, based on data showing that chronic EO inhalation exposure was associated with the occurrence of cancer, reproductive effects, mutagenic changes, neurotoxicity, and sensitization. In 1990, the US Clean Air Act Amendments designated EO as one of 187 hazardous air pollutants (HAPs) and emissions standards were established by US EPA.
Though the hazards of EO have been known for some time, the primary driver of a more recent focus on EO has been the US EPA’s 2016 Integrated Risk Information System (IRIS) report on the inhalation carcinogenicity of EO, which asserted that the long-term exposure risk of EO is much greater than previously thought. This reassessment attributed a 100-in-one-million inhalation cancer risk to a continuous lifetime exposure of 0.011 parts per billion (ppb) EO, approximately 50 times lower than the previous risk assessment (Mei, 2023; US EPA, 2016). To complicate matters, this concentration was and still is significantly lower than what most available analytical instruments can reliably measure.
The 2016 IRIS assessment is not without controversy, and the Texas Commission on Environmental Quality has challenged the US EPA’s risk-specific concentration for EO. Adding to the concern for community groups, data collected and published in 2018 by US EPA from nationwide National Air Toxic Assessment and Air Toxic Screening Assessment sites showed that concentrations of EO were significantly above the concentration specified in the updated risk assessment in many areas of the country, particularly in urban areas. The discovery of elevated concentrations of EO in ambient air prompted an investigation by US EPA into understanding concentrations of “background,” EO (i.e., EO concentrations present in outdoor air at locations clearly not linked to a particular EO source such as a chemical plant of sterilization facility). More research into background concentrations of EO is ongoing.
Adding to an already complex balancing act of the positive and important uses of EO, its negative impact on human health, and new regulatory requirements, EO is also a notoriously difficult compound to analyze. It is a highly reactive compound, making it difficult to collect a stable samples and creating a challenge in keeping laboratory calibration standards stable over time. Several of the established monitoring methods for EO focus on worker exposure limits by pumping air through sorbent tube samplers over a specified time window, resulting in a time-weighted average (TWA) concentration (OSHA, 2014). Alternatively, there are established methods for measuring EO emissions directly from an industrial facility stack using gas chromatography. Though these methods have been used for decades, they do not provide the sensitivity necessary to measure EO at the very low concentration specified in the 2016 risk assessment.
Currently, EO in ambient air is most commonly measured by US EPA Method TO-15 or TO-15A, widely adopted methods where air is collected into a specially treated canister and analyzed in a laboratory with gas chromatography/mass spectrometry (GC/MS). These are validated methods for measuring ambient volatile organic compounds (VOCs). Although analysis of EO is included in these methods, validation did not fully address EO-specific issues such as interferences. US EPA has acknowledged several challenges with this methodology when analyzing low concentrations of EO. One challenge is the presence of interfering species with identical molecular weights to EO, complicating the GC/MS analysis, and another is that leaks have been found to develop in certain types of standalone canister sample timers during TO-15 sampling. Perhaps most problematic for EO, is that positive measurement bias has been documented due to a poorly understood “growth effect,” in which the EO concentration, when collected in certain canister types or exposed to certain humidity levels, continues to “grow” significantly post sample collection (Hoisington, 2021; US EPA, 2021a). These specific challenges with TO-15 for EO analysis specifically have been documented by US EPA and are currently being investigated further, with a specific addendum to TO-15 for EO analysis expected in the future (US EPA, 2021b).
The recent EO regulations and limitations of existing sampling and analytical technologies have also driven the development and adoption of novel EO monitoring techniques. While most of the existing methods for EO analysis are limited to either discrete “grab” samples or time-integrated samples that are collected over a specified length of time and the concentration reported as a TWA, many of the emerging technologies focus on real-time or near real-time analysis of EO. This provides the added advantage of being able to time-resolve when discrete EO events are occurring and eliminating hold-time concerns and the requirement for offline laboratory analysis and associated turnaround times. Proton-transfer reaction-mass spectrometry (PTR-MS), cavity ring down spectroscopy (CRDS) and Fourier transform infrared spectroscopy (FTIR) are some of the analytical techniques utilized by these deployable, real-time analyzers (Sonoma, 2023). In the past 4 years, at least seven new analytical instruments have been developed and marketed specifically for the analysis of EO. Some of these technologies, such as FTIR, have been adopted in newer US EPA methods for analysis of source emissions, but none have been validated or approved for ambient air monitoring as of yet. US EPA’s Office of Research and Development is currently evaluating several of these novel technologies and many have shown promise in measuring low ppt concentrations of EO in ambient air, approaching the long-term exposure risk threshold.
As EO measurement techniques and technologies continue to evolve, so do EO regulations. By March 1, 2024, US EPA is expected to finalize three more key proposed actions,
- Reduce EO emissions from commercial sterilization facilities.
- Reduce EO emissions from chemical manufacturers.
- Reduce risk for workers exposed to EO at their jobs, as well as communities near sterilization facilities.
Additional US EPA actions are expected in 2024-2025 regarding emissions from hospitals with EO sterilizers. One thing is certain, it is a complex issue given EO’s widespread use and utility, current limitations and emerging measurement technologies, adverse human health impacts and changing regulatory actions intended to limit exposure. It will continue to evolve for the foreseeable future as regulations, technology, and our understanding of EO continue to advance. Stay tuned!
Senior Forensic Chemist
Rock J. Vitale, CEAC
Technical Director of Chemistry
Hoisington, J., and Herrington, J. S., 2021. Rapid Determination of Ethylene Oxide and 75 VOCs in Ambient Air with Canister Sampling and Associated Growth Issues. Separations, 8(3), 35. MDPI AG. http://dx.doi.org/10.3390/separations8030035
Mei, E. J., Moore, A. C., & Kaiser, J., 2023. Suitability of new and existing ambient ethylene oxide measurement techniques for cancer inhalation risk assessment. Environmental Pollution, 336, 122481. https://www.sciencedirect.com/science/article/pii/S0269749123014835
OSHA, 2014. Ethylene Oxide Method 1010, Revision 2. March 2014. https://www.osha.gov/sites/default/files/methods/osha-1010.pdf
Sonoma Technologies, 2023. Emerging Technologies for Measuring Ambient Ethylene Oxide. Sonoma Technologies Blog. https://www.sonomatech.com/node/351
US EPA, 2016. Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (Final Report). U.S. Environmental Protection Agency, Washington, DC, EPA/635/R-16/350F. https://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=329730.
US EPA, 2021(a). Technical Note: The Ethylene Oxide (EtO) Canister Effect. May 25, 2021. https://www.epa.gov/sites/default/files/2021-05/documents/technical-note-on-eto-canister-effect- 052521.pdf
US EPA, 2021(b). Ethylene Oxide Measurements Method TO-15/TO-15A Overview, Challenges, Resources and Next Steps. April 15, 2021. https://www.epa.gov/sites/default/files/2021- 05/documents/eto-technical-webinar-041521-w-qandas.pdf