Ethylene Oxide

Full Profile

General Information

Ethylene oxide is a colourless gas with a characteristically sweet, ether-like odour.^[2,3] It is highly flammable and dissolves easily in water, alcohol, and most organic solvents.^[3] Produced since the early 1900's, ethylene oxide has been used as a chemical intermediate and as a sterilizing agent.^[4] Ethylene oxide may also be referred to as oxirane and EtO.^[4] There are numerous other synonyms and product names; see the Hazardous Substances Data Bank (HSDB) for more information.^[5]

Ethylene oxide was classified in 1994 by the International Agency for Research on Cancer (IARC) as Group 1, carcinogenic to humans.^[4] The Volume 100 IARC review reaffirmed this classification, finding limited evidence in humans and sufficient evidence in animals for lymphatic and haematopoietic cancers, as well as breast cancer.^[6] Mechanistic studies provided strong support for the Group 1 designation, as EtO is a potent alkylating agent, frequently showing genotoxic effects.^[7] The effective sterilizing properties of EtO and its carcinogenicity both arise from its capacity to damage DNA.^[2]

Ethylene oxide can irritate the eyes, skin, and respiratory system, and can cause central nervous system effects.^[3] With chronic exposure, neurological effects including memory loss, peripheral neuropathies, and impaired coordination have been reported.^[3] Asthmatic reactions can occur in individuals sensitized to EtO.^[7] There is limited evidence that EtO exposure may be associated with increased risk of miscarriage.^[3]

How did CAREX choose this agent for review?

Regulations and Guidelines

Occupational Exposure Limits (OEL) ^{[28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]}

Canadian Jurisdictions	OEL (ppm)
Canada Labour Code	1
AB, MB, NB, NL, NS, PE, QC	1
BC	0.1 [rep] 1 [stel, rep]
NT, NU, SK	1 2 [stel]
ON	1 10 [stel]
YT	50 75 [stel]
Other Jurisdiction	OEL (ppm)
ACGIH 2018 TLV	1

Canadian Environmental Guidelines

Jurisdiction	Limit	Year
Ontario Ambient Air Quality Criteria	Annual: 0.04 µg/m3	2016[8]
	24 hour: 0.2 µg/m3	2016[8]
Alberta Ambient Air Quality Objectives and Guidelines	1 hr: 15 μg/m3	2017[9]
BC's Contaminated Sites Regulation, BC Reg 375/96	Sets vapour standards for: Agricultural, urban park, residential, commercial, and industrial air: 10 μg/m3 (Vapours derived from soil, sediment, or water)	2017[10]
Cosmetic Ingredients Hotlist	Not Permitted	2014[11]
PMRA	Registered for use as a bactericide	2016[12]
Health Canada's Maximum Residue Limits for food	Food type: Vanilla: 7 ppm Juniper berries: 7 ppm Dried spices (e.g. black pepper, cinnamon, cumin, safron, thyme): 7 ppm	2017[43]

EtO use is also monitored through the Pest Control Products Act. In order to reduce duplication in regulatory oversight, EtO was removed from Health Canada's List of Permitted Food Additives with "Other Generally Accepted Uses (List 8)" in 2016.^[13] Ethylene oxide was not included in other Canadian government environmental guidelines reviewed.^[14,15]

Canadian Agencies/Organizations

Agency	Designation/Position	Year
Health Canada	DSL – low priority substance (already risk managed)*	2006[16]
CEPA	Schedule 1, paragraph 'c'	1999[17]
National Classification System for Contaminated Sites	Rank = "High hazard"; confirmed human carcinogen	2008[18]
Environment Canada's National Pollutant Release Inventory	Reportable to NPRI if manufactured, processed, or otherwise used at quantities greater than 10 tonnes.	2016[44]

Ethylene oxide was not included in other Canadian government chemical listings reviewed. ^[19]

Main Uses

Ethylene oxide is used as a chemical intermediate, primarily to produce ethylene glycol (antifreeze).^[2]

Smaller amounts of EtO are used as sterilizing agents, disinfectants, fumigants, or insecticides.^[2] Medical facilities (hospitals, medical and dental clinics) and manufacturers of sterile medical supplies account for the majority of its use as a sterilant.^[2] In Canada, approximately 120 healthcare facilities use ethylene oxide as a sterilant.^[20]

Other applications where EtO is used as a sterilant include heat sensitive materials such as furs, furniture, beehives, cosmetics, drugs, and tobacco,^[2] and in publication and wood products industries.^[6]

Ethylene oxide is used as a fumigant to control bacteria in spices and natural seasonings and to control insects in stored products.^[6] There is one product listed with ethylene oxide as an active ingredient registered with the Canadian Pest Management Regulatory Agency (PMRA).^[21]

Canadian Production and Trade

Production and Trade

Activity	Quantity	Year
Canadian Production	108,400 t	2004[4]
Export	0 t of 'oxirane (ethylene oxide)'	2015[22]
Import	7,152 t of 'oxirane (ethylene oxide)'	2015[22]

Occupational Exposures

Inhalation is the most important route of occupational exposure to ethylene oxide.^[3]

Although the majority of ethylene oxide is used to produce chemicals, most occupational exposure occurs through its use in sterilization, particularly of medical equipment.^[2,19] The highest exposures have been measured in facilities using EtO as a sterilant or fumigant, including hospitals, healthcare facilities, and spice manufacturers.^[23] Workers may be exposed while changing ethylene oxide gas cylinders; from leaking equipment; from improper ventilation at the sterilizer door, discharge line, aerators, and in the general room; during removal and transfer of items from the sterilizer to an aerator; and from incomplete aeration of items.^[2] Ethylene oxide is registered for use as a disinfectant in six products listed in the Drug Products Database of Health Canada.^[24] Some studies show that exposures during sterilization procedures can be effectively controlled by industrial hygiene measures.^[2] Current average concentrations of ethylene oxide in hospitals and production facilities have decreased substantially from historical levels, to <2 mg/m³ in western Europe and North America.^[2]

There is potential for exposure to EtO during production of industrial chemicals. However, these processes are usually automated and contained in closed systems, which minimizes exposure.^[23] Exposures in the chemical industry occur mainly during loading and unloading of transport tanks, product sampling, and equipment maintenance and repair.^[25]

Environmental Exposures

There is limited data in Canada on the general population's exposure to ethylene oxide, but the most important route of exposure is inhalation.^[6] In one national study of 50 ambient air samples taken over 24 hours in randomly selected residential areas, 94% of the samples were below the detection limit.^[6] The same study, looking at indoor air, reported 98% of samples below the limit of
detection.^[6]

Sources of environmental exposure to EtO are mainly products that have been sterilized with the compound, including medical products, foods, clothing, cosmetics, and beekeeping equipment.^[2] A minor source of exposure to ethylene oxide is gasoline combustion and cigarette smoke (either residue from fumigation of tobacco, or as a combustion by-product).^[3,6]

Data on EtO levels in water, soil, sediment and groundwater in Canada were not identified.^[6]

Searches for EtO in Environment Canada's National Pollutant Release Inventory (NPRI) and the United States Household Products Database yielded the following results on current potential for exposure to EtO in Canada:

NPRI and US Household Products Database

NPRI 2015[26]
Substance name: 'Ethylene oxide'
Category	Quantity	Industry
Released into Environment	2.2 t	Chemical manufacturing (4 facilities)
Disposed of	22 t
Sent to off-site recycling	None

US Household Products 2016[27]
Search Term	Quantity	Product Type
'ethylene oxide'	10	Coolant (1), transmission fluid (1), auto sealant (1), cleaner (4), laundry detergent (1), rust removers (1), and pet flea & tick control (1)

Exposure Reduction

Our team has performed a detailed scan of exposure control resources and assembled a compilation of key publications and resources. These are organized by type of exposure (environmental or occupational) and by specificity (general or carcinogen-specific). Please visit our Exposures Reduction Resources page to view.

We also recommend exploring the Prevention Policies Directory, a freely-accessible online tool offering information on policies related to cancer and chronic disease prevention. Providing summaries of the policies and direct access to the policy documents, the Directory allows users to search by carcinogen, risk factor, jurisdiction, geographical location, and document type. Click here to learn more about policies specific to ethylene oxide on the Directory. For questions about this resource, please contact a member of the Prevention Team at the Canadian Partnership Against Cancer at primary.prevention@partnershipagainstcancer.ca.

Sources

1. Wikimedia. Wikimedia Commons Photograph: Ethylene Oxide
2. National Toxicology Program (NTP). 14th Report on Carcinogens for Ethylene Oxide (2016) (PDF)
3. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Ethylene oxide (1990) (PDF)
4. International Agency for Research on Cancer (IARC). Monograph summary, Volume 97 (2008) (PDF)
5. US National Library of Medicine. Hazardous Substances Data Bank (Search term: 'Ethylene oxide')
6. International Agency for Research on Cancer (IARC). Monograph summary, Volume 100 Part F (2012) (PDF)
7. Health Canada. Priority Substances List assessment report (CEPA) for Ethylene oxide (2001) (PDF)
8. Ontario Ministry of the Environment and Climate Change. Ontario's Ambient Air Quality Criteria (2016)
9. Alberta Environment and Parks. Ambient Air Quality Objectives (2017)
10. Government of British Columbia. Contaminated Sites Regulation B.C. Reg. 375/96 (2017)
11. Health Canada. Cosmetic Ingredient Hotlist (2014)
12. Health Canada. Pesticide Label Search (2016)
13. Canada Gazette. Regulations Amending the Food and Drug Regulations (Food Additives) (2016)
14. Health Canada. Guidelines for Canadian Drinking Water Quality (2017) (PDF)
15. Health Canada. Exposure Guidelines for Residential Indoor Air Quality (1987) (PDF)
16. Health Canada. Prioritization of the DSL (2006)
17. Environment and Climate Change Canada. CEPA List of Toxic Substances (1999)
18. Canadian Council of Ministers of the Environment (CCME). National Classification System for Contaminated Sites (2008) (PDF)
19. Government of Canada. Chemicals Management Plan - List of all Challenge Substances (2010)
20. Grosse, Y. et al. "Carcinogenicity of 1,3-butadiene, ethylene oxide, vinyl chloride, vinyl fluoride, and vinyl bromide." Lancet Oncol 2007;8(8):679-680.
21. Health Canada. Product Label Search (2016)
22. International Trade Centre. TradeMap (Free subscription required)
23. World Health Organization (WHO). CICAD No. 54: Ethylene oxide (2003) (PDF)
24. Health Canada. Drug Product Database (2009)
25. World Health Organization (WHO). Concise International Chemical Assessment Document 54: Ethylene Oxide (2003)
26. Environment and Climate Change Canada. National Pollutant Release Inventory (NPRI) Facility Search (Substance name: 'Ethylene oxide')
27. US Household Products Database (HPD). Household Products (Search term: 'Ethylene oxide')
28. Ministry of Justice. Canada Occupational Health and Safety Regulations (SOR/86-304) (2018)
29. The Canadian Legal Information Institute (CanLII). Yukon's Occupational Health Regulations, O.I.C. 1986/164 (2012) (PDF)
30. Government of Alberta. Occupational Health and Safety Code. Occupational Health and Safety Act 568 (2009) (PDF)
31. WorkSafeBC. Occupational Health and Safety Regulation, BC Reg 296/97, Part 5 (2018)
32. Government of Manitoba. Manitoba Regulation 217/2006 Workplace Safety and Health Regulation (2015) (PDF)
33. The Canadian Legal Information Institute (CanLII). Government of New Brunswick's General Regulation 91-191, under the Occupational Health and Safety Act (2018)
34. Government of Newfoundland and Labrador. Regulation 5,12 Occupational Health and Safety Regulations (2012)
35. Government of the Northwest Territories. Occupational Health and Safety Regulations, R-039-2015 (2016) (PDF)
36. Government of Nova Scotia. Workplace Health and Safety Regulations made under Section 82 of the Occupational Health and Safety Act (2014)
37. The Canadian Legal Information Institute (CanLII). Government of Nunavut's Occupational Health and Safety Regulations, Nu Reg 003-2016 (2010)
38. Ontario Ministry of Labour. Current Occupational Exposure Limits for Ontario Workplaces Required Under Regulation 833 (2017)
39. Government of Prince Edward Island. Occupational Health and Safety Act Regulations Chapter 0-1 (2013) (PDF)
40. Government of Quebec. Regulation Respecting Occupational Health and Safety (2015)
41. Government of Saskatchewan. The Occupational Health and Safety Regulations, 1996 (2016) (PDF)
42. Occupational Safety and Health Administration (OSHA). Annotated PELs (2018)
43. Health Canada. Maximum Residue Limits for Pesticides (2018)
44. Environment Canada. National Pollutant Release Inventory: Substance list (2017)

Other Resources

1. Agency for Toxic Substances and Disease Registry (ATSDR). ToxFAQ Sheet for Ethylene Oxide (1999) (PDF)