1,4-Dioxane Profile

INDUSTRIAL CHEMICALS  POSSIBLE CARCINOGEN (IARC 2B)

CAS No. 123-91-1
IARC Monograph Vol. 71, 1999 (Group 2B)

1,4-Dioxane Profile

General Information

1,4-dioxane is a clear and colourless liquid[1] with a faint, pleasant odour.[2] It is a synthetic industrial chemical used as a stabilizer and a solvent.[3] It may also be referred to as dioxane, 1,4-diethylene dioxide, or diethylene oxide.[4] There are numerous other synonyms and product names; see Hazardous Substances Data Bank (HSDB) for more information.[4]

1,4-dioxane is classified by the International Agency for Research on Cancer (IARC) as Group 2B, possibly carcinogenic to humans, based on data in experimental animals.[5] When administered orally to mice, rats and guinea pigs, 1,4-dioxane produced increased incidences of tumours in a variety of sites including the skin, liver, nasal cavity, and mammary gland.[5]

There is insufficient evidence to assess the carcinogenicity of 1,4-dioxane in humans. In a small occupational study between 1954 and 1975, mortality rates were not elevated in workers exposed to low concentrations of 1,4-dioxane.[6]

Additional adverse health effects of exposure to 1,4-dioxane include liver and kidney damage, resulting from high levels of exposure.[2] Eye and nose irritation is reported from short term, low level exposure.[2]

Regulations and Guidelines

Occupational exposure limits (OEL) [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]

Canadian Jurisdictions OEL (ppm)
Canada Labour Code 20 [sk]
BC, AB, MB, ON, QC, NL, PE, NS 20 [sk]
SK, NT, NU 20 [sk]
30 [stel]
NB 20 [sk]
YT 50 [sk]
50 [stel]
Other Jurisdiction OEL (ppm)
ACGIH 2020 TLV 20 [sk]
ppm = parts per million
sk = easily absorbed through the skin
stel = short term exposure limit (15 min. maximum)
ACGIH = American Conference of Governmental Industrial Hygienists
TLV = threshold limit value

Canadian environmental guidelines and standards*

Jurisdiction Limit Year
Cosmetic Ingredients Hotlist Not Permitted 2004[22]
BC’s Contaminated Sites Regulation, BC Reg 375/96 Sets soil standards for the protection of human health:
Agricultural and low density residential sites: 70 μg/g
Urban park and high density residential sites: 150 μg/g
Commercial and industrial sites: 350 μg/g

 

Drinking water: 1.5 μg/L

2017[23]
Ontario’s Ambient Air Quality Criteria 24 hour: 3,500 μg/m3 2016[24]
*Standards are legislated and legally enforceable, while guidelines (including Ontario ambient air quality criteria) describe concentrations of contaminants in the environment (e.g. air, water) that are protective against adverse health, environmental, or aesthetic (e.g. odour) effects

Canadian agencies/organizations

Agency Designation/Position Year
Health Canada DSL – high priority substance
with the greatest potential for exposure
2006[25]
Challenge to Industry Batch 7 (Health) 2008[26]
National Classification System for Contaminated Sites Rank= “High hazard”,
potential human carcinogen
2008[27]
Environment Canada’s National Pollutant Release Inventory Reportable to NPRI if manufactured, processed, or otherwise used at quantities greater than 10 tonnes 2016[28]
DSL = domestic substance list

1,4-dioxane was not included in other Canadian government guidelines, standards, or chemical listings reviewed.

Main Uses

Historically, 1,4-dioxane was used to stabilize a chemical called 1,1,1-trichloroethane (TCA).[2] TCA use was limited in the US in 1996 due to its ozone-depleting properties, making 1,4-dioxane use for this purpose no longer significant.[2]

Currently, 1,4-dioxane is used as a laboratory reagent and as a solvent to produce cellulose acetate, ethyl cellulose, benzyl cellulose, lacquers, plastics, varnishes, paints, dyes, resins, oils, fats, waxes, greases, polyvinyl polymers, and wood pulp.[1] It has also been used as a chemical intermediate, catalyst for polymerization, and an extraction medium, as well as in plastic, rubber, and pesticide production.[2]

1,4-dioxane also has a minor use as a working fluid for measuring radioactivity and optical activity, and purifying drugs. It can also act as a spectroscopic-photometric solvent and a manufacturing agent for membrane filters.[4]

Canadian Production and Trade

Activity Quantity Year
Canadian Production 10 – 100 t 2006[29]
Export: N/A None 2021[30]
Import: N/A None 2021[30]
t = tonne
 

Environmental Exposures Overview

Although there is little quantitative data regarding levels of exposure to the general population, sources of 1,4-dioxane (in order of expected importance) are ambient and indoor air, drinking water, food, and dermal exposure from consumer products.[31]

Recent air monitoring data is not available. However, concentrations are expected to be higher near point sources such as contaminated sites.[31]

1,4-dioxane in tap water may volatilize during showering, bathing, and laundering, which creates a source of exposure.[31] 1,4-dioxane is soluble in water and can leach through soil into groundwater.[31]

Food may become contaminated through packaging made from 1,4-dioxane-containing materials, or crops treated with pesticides containing 1,4-dioxane.[1,32] However, since dioxane is not registered in Canada for use in pesticides either as an active ingredient or in any formulations,[33,34] this is not likely to be a source of exposure.

Residual levels of 1,4-dioxane may be found in consumer products including detergents, shampoos, cosmetics, and pharmaceuticals.[31] During manufacturing of these products, 1,4-dioxane can be formed as a by-product when ethylene oxide or ethylene glycol are condensed.[31] Although current practice is to remove 1,4-dioxane prior to adding ethoxylated compounds, impurities may still be a concern.

Historically, 1,4-dioxane was rarely investigated during site assessments and remediation because past methods of analysis did not reliably detect the compound.[35] There is currently a growing body of knowledge to address remediation and the Environmental Protection Agency (EPA) has classified 1,4-dioxane as an “Emerging Contaminant”.[3]

Sites typically contaminated with 1,4-dioxane include solvent release sites, and areas where wastewater is discharged from polyethylene terephthalate (PET) plastic manufacturing.[3] An internet product search yielded 31 suppliers of PET plastic and products in Canada.

Searches of environmental and consumer product databases yielded the following results on the potential for exposure to 1,4-dioxane in Canada:

NPRI and US Consumer Product Information Database

NPRI 2015[36]
Search term: ‘1,4-Dioxane’
Category Quantity Industry
Released into Environment 5 t Basic chemical manufacturing
(2 facilities)
Disposed of None
Sent to off-site recycling None
US Consumer Products 2016[37]
Search Term Quantity Product Type
‘1,4-dioxane’ 3 Adhesives & pet care: pesticidal shampoo
t = tonne

Occupational Exposures Overview

Both inhalation and dermal contact are important routes of occupational exposure to 1,4-dioxane.[38]

CAREX Canada estimates that approximately 3,000 Canadian are exposed to 1,4-dioxane in the workplace. The industry with the largest number of workers exposed to 1,4-dioxane is pharmaceutical and medicine manufacturing, followed by professional, scientific, and technical services. The largest occupational groups exposed are chemical technologists and technicians followed by chemists and chemical plant machine operators.

A European occupational exposure assessment developed models for three exposure scenarios including producing 1,4-dioxane, formulating products that contain it, and end-use (either of dioxane itself or products containing it).[38] Dermal exposures were predicted to be highest during the use of dioxane-containing metal cleaning products (1.5 mg/cm2 skin/day). Estimates of inhalation exposure were highest during product formulation; for example adding 1,4-dioxane, and mixing and bagging the final product (typical concentration estimated at 40 mg/m3).

For more information, see the occupational exposure estimate for 1,4-dioxane.

Sources

1. National Toxicology Profile (NTP). 14th Report on Carcinogens for 1, 4-Dioxane (2016) (PDF)
2. The Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for 1,4-dioxane Draft (2012) (PDF)
3. Environmental Protection Agency (EPA). Technical Fact Sheet – 1,4-Dioxane November (2017) (PDF)​
4. US National Library of Medicine. PubChem (Search term: ‘dioxane’)​
5. International Agency for Research on Cancer (IARC). Monograph summary, Volume 71 (1999) (PDF)
6. Buffler P, et al. “Mortality follow-up of workers exposed to 1,4-dioxane.” Journ of Occ Med 1978;20:259.
10. The Canadian Legal Information Institute (CanLII) Manitoba Regulation 217/2006 Workplace Safety and Health Regulation (2022)
12. Government of Newfoundland and Labrador. Regulation 5,12 Occupational Health and Safety Regulations (2018)
13. Government of the Northwest Territories. Occupational Health and Safety Regulations, R-039-2015 (2020) (PDF)
15. The Canadian Legal Information Institute (CanLII). Government of Nunavut’s Occupational Health and Safety Regulations, Nu Reg 003-2016 (2010)
17. Government of Prince Edward Island. Occupational Health and Safety Act Regulations Chapter 0-1 (2013) (PDF)
19. The Canadian Legal Information Institute (CanLII) The Occupational Health and Safety Regulations, 1996 (2022)
20. The Canadian Legal Information Institute (CanLII). Yukon’s Occupational Health Regulations, O.I.C. 1986/164 (2020) (PDF)
21. Occupational Safety and Health Administration (OSHA). Annotated PELs (2020)
22. Health Canada. Cosmetic Ingredient Hotlist (2019)
23. Government of British Columbia. Contaminated Sites Regulation B.C. Reg. 375/96 (2021)
24. Ontario Ministry of the Environment and Climate Change. Ontario’s Ambient Air Quality Criteria (2019)
27. Canadian Council of Ministers of the Environment (CCME). National Classification System for Contaminated Sites (2008) (PDF)
30. International Trade Centre. TradeMap (Free subscription required)
31. The Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for 1,4-Dioxane (2012) (PDF)
32. Environment and Climate Change Canada. Screening Assessment for the Challenge – 1,4-Dioxane (2010)
35. Environmental Science and Engineering Magazine. 1,4-Dioxane: A Little Known Compound (2002)
36. Environment and Climate Change Canada. National Pollutant Release Inventory (NPRI) data search (2017) (Substance name: ‘1,4-Dioxane’)
37. Consumer Product Information Database (CPID). What’s in it? (2022) (Search term: ‘1,4-Dioxane’)

 

Other Resources

  1. The Agency for Toxic Substances and Disease Registry (ATSDR). ASTDR ToxFAQ Sheet for 1,2-Dioxane (2012) (PDF)
  2. World Health Organization (WHO). Chemical fact sheets: 1,4-Dioxane (2022)
  3. Lesage S, Jackson RE, Priddle MW, Riemann PG. “Occurrence and fate of organic solvent residues in anoxic groundwater at the Gloucester Landfill, Canada.” Environ Sci Tech1990;24:559-565.

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