Hazardous substance assessment – Ethylene glycol

Identification

Chemical name:

Ethylene glycol

CAS #:

107-21-1

Chemical composition:

C₂H₆O ₂

Synonyms:

• 1,2-Ethanediol
• Ethane-1,2-diol

UN #:

No chemical-specific UN # available

Pictogram(s):

Figure 1 – Text description

The symbol within the pictogram is an exclamation mark. This symbol indicates that hazardous products with this pictogram can cause certain health effects for example:

• skin irritation
• eye irritation
• skin sensitization

Figure 2 – Text description

The symbol within the pictogram is a black silhouette of a person's head and chest with a white star shape spreading out from the center of the chest. This symbol indicates that hazardous products with this pictogram can cause certain health effects for example:

• carcinogenicity
• specific target organ effects following single or repeated exposure
• reproductive toxicity

WHMIS classification

Health hazards:

• Acute Toxicity (Oral) – Category 4
• Specific Target Organ Toxicity – Single Exposure – Category 1

Physical hazards:

Ethylene glycol does not meet the criteria for classification.

Health hazards

Acute Toxicity (Oral):

Category 4

Median lethal dose (LD-₅₀): 1 570 milligrams per kilogram of body weight (mg/kg-bw) (human)^{Reference 1}.

The estimated human lethal dose for ethylene glycol is 25 304.8 micromoles per kilogram of body weight (1 570 mg/kg-bw) ^{Reference 1}. LD₅₀ values in animal studies are not applicable for classifying this substance since ingestion of ethylene glycol is more hazardous to humans.

The available data meet the classification criteria for Acute Toxicity (Oral) – Category 4 [HPR 8.1.1(1)].

Acute Toxicity (Dermal):

Does not meet criteria

LD-₅₀: 10 600 mg/kg-bw (rabbit)^{Reference 2}.

The available data do not meet the classification criteria for a category of Acute Toxicity (Dermal).

Acute Toxicity (Inhalation – Gases):

Not applicable

Ethylene glycol is not a gas. The classification criteria for Acute Toxicity (Inhalation – Gases) do not apply to this substance.

Acute Toxicity (Inhalation – Vapours):

No data available

No data are available to determine whether ethylene glycol meets the classification criteria for a category of Acute Toxicity (Inhalation - Vapours).

Acute Toxicity (Inhalation – Dusts and Mists):

No data available

No data are available to determine whether ethylene glycol meets the classification criteria for a category of Acute Toxicity (Inhalation – Dusts and Mists).

Skin Corrosion / Irritation:

Does not meet criteria

A study conducted by BASF in Vienna White rabbits (n=2) exposed to undiluted ethylene glycol for 20 hours and observed for 8 days reported an overall irritation score of 0 with no signs of irritation^{Reference 3}.

A Draize skin irritation study in rabbits (6 males) exposed to 0.5 mL of undiluted ethylene glycol for 23 hours reported a primary cutaneous irritation index of approximately 0^{Reference 3Reference 4}.

The available data do not meet the classification criteria for a category or subcategory of Skin Corrosion / Irritation.

Serious Eye Damage / Eye Irritation:

Does not meet criteria

A study conducted by BASF in Vienna White rabbits (n=2) exposed to 0.05 mL of undiluted ethylene glycol for 24 hours and observed for 8 days reported no signs of irritation and an overall irritation score of 0^{Reference 3}.

A Carpenter and Smyth study in rabbits exposed to 0.5 mL of undiluted ethylene glycol reported a score of Grade 1, indicating that the test substance is only minimally irritating^{Reference 5}.

The available data do not meet the classification criteria for a category or subcategory of Serious Eye Damage / Eye Irritation.

Respiratory Sensitization:

No data available

No data are available to determine whether ethylene glycol meets the classification criteria for a category or subcategory of Respiratory Sensitization.

Skin Sensitization:

Does not meet criteria

An Organisation for Economic Co-operation and Development (OECD) Test Guideline 406-compliant study in 20 guinea pigs induced intradermally with a 5% aqueous solution of ethylene glycol and epicutaneously with undiluted ethylene glycol and then challenged with undiluted ethylene glycol reported no signs of skin sensitization^{Reference 3}.

The available data do not meet the classification criteria for a category or subcategory of Skin Sensitization.

Germ Cell Mutagenicity:

Does not meet criteria

In vivo:

A dominant lethal assay in rats (15 per dose) fed a dose of 40, 200 or 1 000 milligrams per kilogram of body weight per day (mg/kg-bw/day) of ethylene glycol produced a negative result for genotoxicity and did not lead to statistically significant adverse effects on any of the parameters measured in the 3 mating intervals^{Reference 3Reference 6}.

A chromosomal aberration study in bone marrow cells from male Swiss mice exposed to a dose of 638 mg/kg-bw/day of ethylene glycol by intraperitoneal injection for 2 days did not reveal any signs of genotoxic effectsReference 7.

Administration of ethylene glycol to Swiss mice via gavage at doses up to 1 250 mg/kg-bw caused only a slight increase in micronuclei of erythrocytes that was not dose-related^{Reference 7}.

In vitro:

An OECD Test Guideline 471-compliant (Bacterial Reverse Mutation Test) study in Salmonella typhimurium( S. typhimurium) strains TA 1535, TA 1537, TA 98 and TA 100 and Escherichia colistrain WP2 produced negative results with and without metabolic activation ^{Reference 3}. Another OECD Test Guideline 471-compliant study in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 also produced negative results with and without metabolic activation^{Reference 3}.

An OECD Test Guideline 473-compliant (In Vitro Mammalian Chromosomal Aberration Test) study in Chinese hamster ovary cells produced negative results with and without metabolic activation^{Reference 3}.

An in vitro mammalian cell micronucleus test in mouse lymphoma L5178Y cells also produced negative results with and without metabolic activation^{Reference 8}.

The available data do not meet the classification criteria for a category or subcategory of Germ Cell Mutagenicity.

Carcinogenicity:

Does not meet criteria

Ethylene glycol has been classified by the American Conference of Governmental Industrial Hygienists as A4, not classifiable as a human carcinogen^{Reference 9}.

In a chronic feeding study, mice were fed a dose of ethylene glycol up to 6 000 mg/kg-bw/day in males and up to 12 000 mg/kg-bw/day in females for up to 103 weeks. No significant signs of systemic toxicity or evidence of carcinogenicity were reported^{Reference 10}.

The available data do not meet the classification criteria for a category or subcategory of Carcinogenicity.

Reproductive Toxicity:

Does not meet criteria

Ethylene glycol has been shown to cause developmental toxicity in rats and mice at concentrations that do not result in concurrent maternal toxicity^{Reference 11Reference 12Reference 13Reference 14Reference 15Reference 16Reference 17}. In contrast, studies in rabbits report that ethylene glycol does not result in reproductive toxicity^{Reference 11Reference 12Reference 13Reference 14Reference 15Reference 16Reference 17Reference 18Reference 19Reference 20Reference 21}. The different effects in rodents and rabbits is believed to be due to differences in placental cell-surface transporters that move glycolic acid in or out of the placenta resulting in accumulation or clearance of glycolic acid in the embryo^{Reference 19Reference 22}. In human placenta, the mechanism of glycolic acid clearance is similar to that of rabbits^{Reference 23}; therefore, this would be anticipated to prevent the accumulation of glycolic acid in the fetus when a mother is exposed to ethylene glycol concentrations below those that cause maternal toxicity.

The available data do not meet the classification criteria for a category or subcategory of Reproductive Toxicity.

Specific Target Organ Toxicity – Single Exposure:

Category 1

Oral Route of Exposure: Studies show that ethylene glycol ingestion results in significant toxic effects on the central nervous system (CNS) and kidneys^{Reference 24Reference 25Reference 26Reference 27Reference 28Reference 29Reference 30Reference 31}. Cases in which treatment was delayed or not available have resulted in metabolic acidosis and death due to kidney failure^{Reference 32Reference 33Reference 34}. Multiple reports of CNS effects in humans following ethylene glycol ingestion include drowsiness, stupor, convulsions, paralysis, ataxia, visual deterioration and coma^{Reference 24Reference 25Reference 26Reference 27Reference 28Reference 29Reference 30Reference 31}.

The available data meet the classification criteria for Specific Target Organ Toxicity – Single Exposure - Category 1 based on CNS effects [HPR 8.8.1(2)]. Since kidney effects in humans can result in mortality, the effect on this target organ is covered under Acute Toxicity.

Dermal Route of Exposure: No adverse effects were observed in an acute toxicity study in rabbits^{Reference 2}.

Inhalation Route of Exposure: Human volunteers exposed to aerosolized ethylene glycol could not tolerate concentrations equal to or greater than 200 milligrams per cubic metre (mg/m³) for more than 1 or 2 minutes due to strong respiratory irritation and cough^{Reference 35}. Since these are subjective effects without objective measurements, the results of this study do not meet classification criteria.

The available data meet the classification criteria for Specific Target Organ Toxicity – Single Exposure – Category 1 [HPR 8.8.1(2)].

Specific Target Organ Toxicity – Repeated Exposure :

Does not meet criteria

Oral Route of Exposure: A study equivalent or similar in design to OECD Test Guideline 452 (Chronic Toxicity Studies) in male rats (n=20 per dose) fed diets formulated to deliver a dose of 0, 50, 150, 300 or 400 milligrams of ethylene glycol per kilogram of body weight per day (mg/kg-bw/day) for up to 12 months reported 5 out of 20 rats had died at a dose of 300 mg/kg-bw/day and 4 out of 20 rats had died at a dose of 400 mg/kg-bw/day. Rats dying early at a dose of 300 mg/kg-bw/day or greater had transitional cell hyperplasia with inflammation and hemorrhaging of the bladder wall. Crystal nephropathy (basophilic foci, tubule or pelvic dilatation, birefringent crystals in the pelvic fornix, or transitional cell hyperplasia) affected most rats at a dose of 300 mg/kg-bw/day and higher. No other significant signs of systemic toxicity were reported^{Reference 36}. The doses at which effects occurred are outside the guidance values for classification in a category of this hazard class.

A chronic feeding study was conducted in rats (16 per sex per dose) fed a concentration of 0, 0.1, 0.2, 0.5, 1 or 4% ethylene glycol in the diet for 2 years. Within 2 years there was 100% mortality in male animals at the 1% concentration and females at the 4% concentration. Males on the 4% diet showed a significant decrease in growth. Of the 16 female animals receiving the 4% diet, 15 had oxalate calculi and all 12 examined histopathologically showed calcification of the kidney. Because of the lack of specificity, tubular degeneration alone was not considered indicative of renal damage due to ethylene glycol exposure^{Reference 37}. The doses at which effects occurred are outside the guidance values for classification in a category of this hazard class.

A study equivalent or similar in design to OECD Test Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents) was conducted in Wistar and F344 male rats (10 per dose) fed a diet containing ethylene glycol at a target dose of 0, 50, 150, 500 or 1 000 mg/kg-bw/day for 16 weeks. Crystal deposition in the kidneys and nephropathy were observed in the 500 and 1 000 mg/kg-bw/day Wistar rat dose groups and in the 1 000 mg/kg-bw/day dose group of F344 rats^{Reference 38}. The doses at which effects occurred are outside the guidance values for classification in a category of this hazard class.

Dermal Route of Exposure: A non-guideline study in female CD-1 mice exposed dermally to a dose of 404, 1 677 or 3 549 mg/kg-bw/day of ethylene glycol for 10 days reported no significant signs of systemic toxicity^{Reference 39}.

Inhalation Route of Exposure: In a chronic study, mice and rats were exposed to ethylene glycol vapours at a mean concentration of 398 mg/m³ for 8 hours per day, 5 days per week for 16 weeks, with no significant signs of systemic toxicity reported ^{Reference 35}. Similarly, a 5-day study where rats were exposed to a saturated vapour of ethylene glycol (500 mg/m³) for 28 hours reported no significant signs of systemic toxicity^{Reference 35}.

The available data do not meet the classification criteria for a category of Specific Target Organ Toxicity – Repeated Exposure.

Aspiration Hazard:

No data available

No human data are available and this substance is not a liquid hydrocarbon.

Biohazardous Infectious Materials:

Not applicable

Ethylene glycol is not a microorganism, protein or nucleic acid.

Physical hazards

Explosives:

Not evaluated
Explosives are excluded from the HPA and its regulations. Explosives are regulated under the Explosives Act. For more information, visit Natural Resources Canada.

Flammable Gases:

Not applicable

Ethylene glycol is not a gas. The classification criteria for Flammable Gases do not apply to this substance.

(Flammable) Aerosols:

Not evaluated

Classification of a hazardous product in the Flammable Aerosols or Aerosols hazard class is product dependent.

Oxidizing Gases:

Not applicable

Ethylene glycol is not a gas. The classification criteria for Oxidizing Gases do not apply to this substance.

Gases Under Pressure:

Not applicable

Ethylene glycol is not a gas. The classification criteria for Gases Under Pressure do not apply to this substance.

Flammable Liquids:

Does not meet criteria

Ethylene glycol has a flash point of 111.1°C (closed cup) and a boiling point of 197.5°C ^{Reference 40}. The flash point is higher than the maximum flash point (93°C) that would warrant classification in a category of this hazard class.

The available data do not meet the classification criteria for a category of Flammable Liquids.

Flammable Solids:

Not applicable

Ethylene glycol is not a solid. The classification criteria for Flammable Solids do not apply to this substance.

Self-reactive Substances and Mixtures:

Does not meet criteria

Ethylene glycol has a boiling point of 197.5°C^{Reference 40}. Self-reactive substances and mixtures must have a self-accelerating decomposition temperature of ≤75°C to meet the minimum classification criteria of a category of this hazard class [HPR 7.8.1(3)].

The available data do not meet the classification criteria for a category of Self-reactive Substances and Mixtures.

Pyrophoric Liquids:

Does not meet criteria

Ethylene glycol has an auto-ignition temperature of 395°C^{Reference 40}. Pyrophoric liquids react at room temperature.

The available data do not meet the classification criteria for a category of Pyrophoric Liquids.

Pyrophoric Solids:

Not applicable

Ethylene glycol is not a solid. The classification criteria for Pyrophoric Solids do not apply to this substance.

Self-heating Substances and Mixtures:

Does not meet criteria

Ethylene glycol has an auto-ignition temperature of 395°C^{Reference 40}, which is well above the maximum spontaneous ignition temperature of 50°C for classification [HPR 7.11.1(3)].

The available data do not meet the classification criteria for a category of Self-heating Substances and Mixtures.

Substances and Mixtures Which, in Contact with Water, Emit Flammable Gases:

Excluded from classification

Ethylene glycol is an organic compound that does not contain metals or metalloids and is, therefore, excluded from classification [HPR 7.12.1(1)(a)].

Oxidizing Liquids:

Excluded from classification

Ethylene glycol is an organic compound that contains oxygen that is chemically bonded only to carbon and hydrogen and is, therefore, excluded from classification [HPR 7.13.1(1)(b)].

Oxidizing Solids:

Not applicable

Ethylene glycol is not a solid. The classification criteria for Oxidizing Solids do not apply to this substance.

Organic Peroxides:

Not applicable

Ethylene glycol is not an organic peroxide. The classification criteria for Organic Peroxides do not apply to this substance.

Corrosive to Metals:

No data available

No data are available to determine whether ethylene glycol meets the classification criteria for a category of Corrosive to Metals.

Combustible Dusts:

Not applicable

Ethylene glycol is not a solid. The classification criteria for Combustible Dusts do not apply to this substance.

Simple Asphyxiants:

Not applicable

Ethylene glycol is not a gas. The classification criteria for Simple Asphyxiants do not apply to this substance.

Pyrophoric Gases:

Not applicable

Ethylene glycol is not a gas. The classification criteria for Pyrophoric Gases do not apply to this substance.

Chemicals Under Pressure:

Not evaluated

Classification of a hazardous product in the Chemicals Under Pressure hazard class is product dependent.

Regulatory and other information

Regulatory information:

Hazardous substance assessments are prepared by Health Canada as educational and information resources. Under the HPA, suppliers of hazardous products must, upon the sale or importation of a hazardous product, provide a safety data sheet and label that meet the requirements set out in the HPR.

Other information:

The information and classifications contained in these hazardous substance assessments are based on publicly available sources, such as peer-reviewed literature or reports by international bodies. New information, including proprietary information, could have an impact on the classification of substances or hazardous products containing them. It is the responsibility of the supplier to ensure the accuracy, sufficiency and reliability of their hazardous product classifications.

Last updated:

2024

Prepared by:

Workplace Hazardous Materials Bureau, Health Canada

References