Hazardous substance assessment – Diethylene glycol monobutyl ether (DGBE)

Identification

Chemical name:

Diethylene glycol monobutyl ether (DGBE)

CAS #:

112-34-5

Chemical composition:

C₈H₁₈O ₃

Synonyms:

• 2-(2-butoxyethoxy)ethanol
• Diglycol monobutyl ether
• Diethylene glycol n-butyl ether
• Butoxy diethylene glycol

UN #:

No chemical-specific UN # available

Pictogram(s):

Figure 1 – Text description

The symbol within the pictogram shows a container dripping liquid onto a piece of metal and another container dripping liquid onto a hand. This symbol indicates that hazardous products with this pictogram can:

• damage or destroy metal
• cause irreversible damage to the skin (for example, burns, blisters, scarring)
• produce tissue damage in the eye or vision loss that is irreversible or not fully reversible within 21 days

WHMIS classification

Health hazards:

Serious Eye Damage – Category 1

Physical hazards:

Flammable Liquids – Category 4

Health hazards

Acute Toxicity (Oral):

Does not meet criteria

Oral median lethal dose (LD₅₀): 3 306 milligrams per kilogram of body weight (mg/kg-bw) (rat)^{Référence 1}.

A non-guideline study in rats (5 per sex per dose) gavaged with a dose of 5.0, 4.0, 3.2, 2.5, 2.0, 1.0, 0.5 or 0.05 millilitres of DGBE per kilogram of body weight (mL/kg-bw) reported an LD ₅₀ of 3 306 mg/kg-bw. Clinical signs included imbalance, atony, lateral body position, labile gait, jerky and weak respiration, and anorexia^{Référence 1}.

In a study conducted similarly to the Organisation for Economic Co-operation and Development (OECD) Test Guideline 401, groups of 5 fasted or fed rats were dosed with DGBE via gavage. The LD₅₀ in fasted rats was 7 292 mg/kg-bw. Clinical signs included inactivity, laboured breathing, rapid respiration, anorexia, weakness, tremors and prostration. The LD ₅₀ value for fed rats was higher than that for fasted rats^{Référence 2}.

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

Acute Toxicity (Dermal):

Does not meet criteria

Dermal LD₅₀: 2 764 mg/kg-bw (rabbit)^{Référence 2}.

In a study performed similarly to OECD Test Guideline 402, groups of 5 rabbits received dermal applications of DGBE to clipped and unabraded skin for 24 hours. Doses were 1 701, 3 403, 6 804 and 13 608 mg/kg-bw. The LD ₅₀ was determined to be 2 764 mg/kg-bw and clinical signs included anorexia, depression, tremors and prostration^{Référence 2}.

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

Acute Toxicity (Inhalation – Gases):

Not applicable

DGBE 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 DGBE meets the classification criteria for a category of Acute Toxicity (Inhalation – Vapours).

Acute Toxicity (Inhalation – Dusts and Mists):

Does not meet criteria

Inhalation median lethal concentration (LC₅₀): >1.5 milligrams per litre (mg/L) (rat)^{Référence 1}.

In a non-guideline study, DGBE was administered as an aerosol for 2 hours at a concentration of 3 mg/L to 8 rats. The animals were observed for 8 days after exposure. There were no deaths and the only noted clinical sign was some eye irritation^{Référence 1}. For a 4-hour exposure, the LC₅₀ would be >1.5 mg/L.

The available data do not demonstrate acute toxicity and thus do not meet the classification criteria for a category of Acute Toxicity (Inhalation – Dusts and Mists).

Skin Corrosion / Irritation:

Does not meet criteria

In a skin irritation study performed according to the OECD Test Guideline 404, exposure to 0.5 cubic centimetre (cm³) of undiluted DGBE in 3 rabbits under occlusive conditions resulted in mean scores per animal of 1.67/4, 1.67/4 or 2/4 for erythema and 0/4, 0.33/4 or 1.33/4 for edema. The exposure time is noted as 1 hour or 4 hours. Results were observed after 24, 48 and 72 hours of substance application and the effects were reversible in all animals within 8 days. DGBE showed a potential for skin irritation as evidenced by erythema in 2 out of 3 animals tested. However, the mean scores do not meet classification criterion (b)(i) of the Table to subsection 8.2.2(3) of the HPR^{Référence 1}.

In another study, a single occlusive application of DGBE to the skin of 1 rabbit for 24 hours did not result in any skin reactions. The dose was not provided. Repeated applications to the skin of 1 rabbit for 3 or 4 weeks under occlusive conditions produced slight irritation that included hyperemia, exfoliation, and hair loss, but no scores or dosages were provided by the study for classification evaluation^{Référence 3}.

Another OECD Test Guideline 404-compliant study found DGBE to be non-irritating in 6 rabbits when exposed for 4 hours under occlusive conditions. A volume of 0.5 millilitre (mL) of undiluted DGBE had been applied to a clipped skin area of 25 by 25 millimetres. Average scores across animals were 1.3/4 for erythema and 1.1/4 for edema over 24, 48 and 72 hours; average scores per animal were not reported. Effects were fully reversible within 9 days^{Référence 1}.

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

Serious Eye Damage / Eye Irritation:

Category 1

In an eye irritation study performed according to the OECD Test Guideline 405, application of 0.1 cm³ of undiluted DGBE to the eyes of 3 rabbits resulted in significant eye irritation. Observations were made 24, 48 and 72 hours after substance instillation. Mean scores across animals of 1.22/4 for corneal opacity, 1/2 for iritis, 1/4 for chemosis and 3/3 for conjunctival redness were reported; mean scores per animal were not reported. Corneal and iris effects were not reversible within 21 days, whereas conjunctival redness and chemosis had fully disappeared by day 14^{Référence 1}. As some effects persisted beyond 21 days, classification in Category 1 of this hazard class is warranted [HPR 8.3.2(1)].

In another eye irritation study conducted similarly to OECD Test Guideline 405, 0.1 mL of a 5, 10, 20 (or 25%) or 50% dilution of DGBE, or of undiluted DGBE, was applied to the eyes of 6 rabbits per group. Undiluted DGBE caused moderately severe conjunctivitis, mild blepharitis, mild iritis and mild diffuse keratitis. These effects were most marked at 24 hours post-installation and cleared within 5-14 days. For undiluted DGBE, mean scores over 24, 48 and 72 hours were 1/4 for chemosis (reversible in 5 days) and 0.67/4 for iritis (reversible in 7 days); mean scores per animal were not reported^{Référence 4}.

Another study was conducted in 2 rabbits exposed to 50 microlitres (μL) of undiluted DGBE to the conjunctival sac of 1 eye. Scores were taken after 10 minutes and after 1, 3 and 48 hours. DGBE was not identified to be an eye irritant based on corneal opacity, iritis, conjunctival redness and chemosis scores of 0 after 48 hours post-exposure^{Référence 1}.

In a non-guideline study in rabbits, 0.005 mL of undiluted DGBE was applied to the eyes of 5 rabbits and assessed 24 hours later. DGBE was given an eye injury grade of 5 (maximum score is 10), which meant severe eye injury. The reversibility of the effects was not reported^{Référence 5}.

The available data meet the classification criteria for Serious Eye Damage – Category 1 [HPR 8.3.2(1)].

Respiratory Sensitization:

No data available

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

Skin Sensitization:

Does not meet criteria

In a human patch test, 1 individual who had a medical history of atopy reacted positively to DGBE at a concentration of 1% in aqueous solution^{Référence 6}.

In a guinea pig maximization study conducted similarly to the OECD Test Guideline 406, DGBE was tested at a concentration of 2.5% for the induction dose and undiluted DGBE was used for the challenge dose. No positive reactions were reported at 24 and 48 hours after challenge^{Référence 1}.

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: In an OECD Test Guideline 474-compliant study that followed good laboratory practices (GLP), negative results were obtained for genotoxic activity in a mouse bone marrow micronucleus test. Mice (5 per sex per dose) were gavaged at doses of 0, 330, 1 100 or 3 300 mg/kg-bw of DGBE. No significant increases in the frequencies of micronucleated polychromatic erythrocytes were observed^{Référence 7}.

In vitro: Negative results were obtained in several Ames tests conducted in accordance with OECD Test Guideline 471 in various Salmonella typhimurium strains including TA 98, TA 100, TA 1535, TA 1537 and TA 1538, with and without metabolic activation^{Référence 1Référence 8}. In a gene mutation assay in mouse lymphoma L517BY cells, positive and negative results were obtained with and without metabolic activation, respectively^{Référence 1Référence 8}. A chromosomal aberration test provided negative results in Chinese hamster ovary cells with and without metabolic activation^{Référence 1Référence 9}.

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

Carcinogenicity:

No data available

No data are available to determine whether DGBE meets the classification criteria for a category or subcategory of Carcinogenicity.

Reproductive Toxicity:

Does not meet criteria

In a reproductive toxicity study, female mice (50 per dose) were orally administered a dose of 500 milligrams of DGBE per kilogram of body weight per day (mg/kg-bw/day) for 8 days beginning on day 7 of gestation. No significant effects were observed for pup counts (live and dead), litter weights, pup weights or offspring viability ratios^{Référence 10}.

In a repeat-dose toxicity study, rats were orally administered a dose of 0, 50, 250 or 1 000 mg/kg-bw/day of DGBE for 13 weeks (5 per sex per dose) in the main study, or a dose of 0, 1 000, 1 500 or 2 000 mg/kg-bw/day of DGBE for 2 weeks (10 rats per sex per dose) in a preliminary study. No adverse effects were observed on sperm parameters or testicular histopathology in male rats^{Référence 11}.

In a fertility study, DGBE was orally administered to male and female rats (25 per sex per dose) from 60 or 14 days before mating, respectively, at a dose of 0, 250, 500 or 1 000 mg/kg-bw/day. No adverse effects on fertility, embryos, fetuses, or neonates were found at any dose tested. However, the mean pup weights were slightly reduced during the later stages of lactation among the offspring of the high-dose female rats group (1 000 mg/kg-bw/day)^{Référence 12}. In a teratology study by the same authors, dermal application of a dose of 0, 100, 300 or 1 000 mg/kg-bw/day of DGBE on pregnant rabbits (20 per group) from gestation days 7-18 did not result in fetal malformations or adverse effects on intrauterine survival^{Référence 12}.

In an OECD Test Guideline 415-compliant study, rats (8-10 per sex per dose) were gavaged with DGBE at a dose of 0, 250, 500 or 1 000 mg/kg-bw/day for 9-10 weeks. No adverse effects on menstrual cycle, estrous cycle, fertility or viability of offspring were reported^{Référence 13}.

In another study, rats (25 per sex) were dermally exposed to a dose of 2 000 mg/kg-bw/day of DGBE under occlusive conditions for 6 hours per day, 5 days per week for 13 weeks. Rats were then mated and continued to be treated daily during mating and gestation. No adverse effects on mating indices, pregnancy rates, male fertility indices, parturition data, pup body weights or pup viability were reported^{Référence 14}.

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

Specific Target Organ Toxicity – Single Exposure:

Does not meet criteria

Oral Route of Exposure: A non-guideline study in rats (5 per sex per dose) gavaged with a dose of 5.0, 4.0, 3.2, 2.5, 2.0, 1.0, 0.5 or 0.05 mL/kg-bw of DGBE reported an LD₅₀ of 3 306 mg/kg-bw. Clinical signs included imbalance, atony, lateral body position, labile gait, jerky and weak respiration, and anorexia^{Référence 1}.

In a study conducted similarly to OECD Test Guideline 401, groups of 5 fasted or fed rats and 5 fasted or fed mice were dosed with DGBE via gavage. The LD₅₀ in fasted rats was 7 292 mg/kg-bw. The LD₅₀ in fasted mice was 2 406 mg/kg-bw. Clinical signs included inactivity, laboured breathing, rapid respiration, anorexia, weakness, tremors and prostration^{Référence 2}.

Dermal Route of Exposure: In a study performed similarly to OECD Test Guideline 402, groups of 5 rabbits received dermal applications of DGBE to clipped and unabraded skin for 24 hours. Doses were 1 701, 3 403, 6 804 and 13 608 mg/kg-bw. The LD₅₀ was determined to be 2 764 mg/kg-bw and clinical signs included anorexia, depression, tremors and prostration^{Référence 2}.

The clinical signs observed in the above 3 studies may be associated with the acute toxicity observed and thus were considered under Acute Toxicity.

Inhalation Route of Exposure: In a non-guideline study, DGBE was administered as an aerosol for 2 hours at a concentration of 3 mg/L to 8 rats. The animals were observed for 8 days after exposure. There were no deaths and the only noted clinical sign was some eye irritation^{Référence 1}.

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

Specific Target Organ Toxicity – Repeated Exposure:

Does not meet criteria

Oral Route of Exposure: In a non-guideline study, rats (10 per dose) were gavaged with a dose of 0, 891, 1 782, or 3 564 mg/kg-bw/day of DGBE for 5 days per week for 6 weeks. No significant signs of systemic toxicity were reported^{Référence 2}.

In a another study, rats (5 per sex per dose) were administered a dose of 0, 50, 250, or 1 000 mg/kg-bw/day of DGBE in drinking water for 13 weeks. No significant signs of systemic toxicity were reported^{Référence 11}.

An OECD Test Guideline 408-compliant (Repeated Dose 90-Day Oral Toxicity Study in Rodents) study was conducted in rats (10 per sex per dose) exposed to a dose of 50, 250 or 1 000 mg/kg-bw/day of DGBE in drinking water for 90 days. No mortality or adverse signs of toxicity were reported^{Référence 1}.

A study conducted similarly to OECD Test Guideline 408 in rats (16 per sex per dose) gavaged with a dose of 65, 327 or 1 630 mg/kg-bw/day (males) or 51, 254 or 1 270 mg/kg-bw/day (females) of DGBE for 5 days per week for 13 weeks reported mortality in 80-90% of the high-dose animals and in 60% of males and 30% of females in the mid-dose group^{Référence 1Référence 15}. In the mid- and low-dose females, a decrease in white blood cell count and lymphocytes was observed. In the mid- and low-dose males, an increase in serum creatinine was observed. The doses at which mortality was observed exceed the guidance values for classification in a category of this hazard class. The hematological and clinical chemistry changes alone do not demonstrate significant toxicity and would not support classification in a category of this hazard class.

In a study conducted similarly to OECD Test Guideline 407, rats (10 per sex per dose) were gavaged with a dose of 891, 1 781 or 3 564 mg/kg-bw/day of DGBE for 28 days. Rats in the 3 564 mg/kg-bw/day dose group had increased mortality, dyspnea, prostration, unkempt hair, decreased body weight and food consumption, splenic congestion, proteinaceous casts in the kidneys and renal hemosiderin^{Référence 1}. The doses tested exceed the guidance values for classification in a category of this hazard class.

Dermal Route of Exposure: In a 13-week study, male and female rats were dermally exposed to a dose of 200 to 2 000 mg/kg-bw/day of DGBE for 6 hours per day, 5 days per week. No significant signs of systemic toxicity were reported^{Référence 1}.

Inhalation Route of Exposure: In a sub-chronic study, rats (10 per sex per group) were exposed to the saturated vapour concentration (22 parts per million [ppm], or 0.143 mg/L) of DGBE for 6 hours per day for 4 days. No significant signs of systemic toxicity were reported^{Référence 16}.

In a repeat-dose study, rats (15 per sex per dose) were exposed to a nominal concentration of 0, 2, 6 or 18 ppm (0, 0.013, 0.039 and 0.117 mg/L, respectively) of DGBE vapours for 6 hours per day, 5 days per week for 5 weeks. No significant signs of systemic toxicity were reported^{Référence 2Référence 17}.

In an OECD Test Guideline 413-compliant study, rats (10 per sex per dose) were exposed to a nominal concentration of 2, 6 or 14 ppm (measured: 0.013, 0.04 and 0.094 mg/L, respectively) of DGBE vapours for 6 hours per day for 90 days. No significant signs of systemic toxicity were reported^{Référence 1}.

In an OECD Test Guideline 412-compliant study, rats (10 per sex per dose) were exposed to a concentration of 0.35 mg/L of DGBE aerosol for 6 hours per day, 5 days per week for 28 days. No significant signs of systemic toxicity were reported^{Référence 1}.

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 DGBE is not a liquid hydrocarbon.

Biohazardous Infectious Materials:

Not applicable

DGBE is not a microorganism, protein, or nucleic acid.

Physical hazards

Explosives:

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

Flammable Gases:

Not applicable

DGBE 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

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

Gases Under Pressure:

Not applicable

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

Flammable Liquids:

Category 4

DGBE has a flash point of 78°C (closed cup)^{Référence 18}.

The available data meet the classification criteria for Flammable Liquids – Category 4 [HPR 7.6.1(2)].

Flammable Solids:

Not applicable

DGBE 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

DGBE has a boiling point of 232°C^{Référence 19}. 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

DGBE has a flash point of 78°C (closed cup)^{Référence 18}. 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

DGBE 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

DGBE has a boiling point of 232°C (measured)^{Référence 19}, 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

DGBE has a chemical structure that does not contain metals or metalloids, and is, therefore, excluded from classification [HPR 7.12.1(1)(a)].

Oxidizing Liquids:

Does not meet criteria

Paragraph 7.13.1(1)(b) of the HPR excludes from classification any organic liquid that contains oxygen, fluorine or chlorine if those elements are chemically bonded only to carbon or hydrogen. DGBE contains oxygen which is chemically bonded only to carbon and hydrogen.

Oxidizing Solids:

Not applicable

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

Organic Peroxides:

Not applicable

DGBE 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 DGBE meets the classification criteria for a category of Corrosive to Metals.

Combustible Dusts:

Not applicable

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

Simple Asphyxiants:

Not applicable

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

Pyrophoric Gases:

Not applicable

DGBE 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