Hazardous substance assessment - 2-Mercaptoethanol

Identification

Chemical name: 

2-Mercaptoethanol

CAS # :

60-24-2

Chemical composition :

C₂H₆OS

Synonyms:

Mercaptoethanol; Ethanol, 2-Mercapto; Beta-mercaptoethanol; 1-ethanol-2-thiol; 2-hydroxy-1-ethanethiol; Thioglycol.

UN #:

2966

Pictogram(s):

Figure 1 - Text description

The symbol within the pictogram is a human skull with 2 crossed bones behind it. The symbol indicates that hazardous products with this pictogram can cause death or poisoning.

Figure 2 - 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

Figure 3 - 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

WHMIS classification

Health Hazards:

Acute Toxicity (Oral) – Category 3

Acute Toxicity (Dermal) – Category 2

Acute Toxicity (Inhalation) – Category 2

Serious Eye Damage - Category 1

Skin Sensitization – Category 1A

Physical Hazards:

Flammable Liquids: Category 4

Health hazards

Acute Toxicity (Oral):

Category 3

Median lethal dose (LD₅₀): (rat, male) 300 mg/kg ^{Footnote 1}. This value is from a range finding test by Smyth and Carpenter.

The available data meet the classification criteria for Acute Toxicity (Oral) – Category 3 [HPR 8.1.1(1)].

Acute Toxicity (Dermal):

Category 2

LD₅₀: (rabbit, male) 168 mg/kg ^{Footnote 2}.

In a study conducted similar to the Organisation for Economic Co-operation and Development Test Guideline (OECD TG) 402, rabbits (6/dose; 3 males, 3 females) were dermally administered 100, 200, 500, 1,000, or 2,000 mg/kg of 2-mercaptoethanol ^{Footnote 2}. All rabbits died at doses ≥ 500 mg/kg bw. Two males died at 200 mg/kg. All other animals survived. The LD₅₀ was determined to be 168 mg/kg (males), 316 mg/kg (females) or 251 mg/kg (combined).

The available data meet the classification criteria for Acute Toxicity (Dermal) – Category 2 [HPR 8.1.1].

Acute Toxicity (Inhalation – Gases):

Not applicable

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

Acute Toxicity (Inhalation – Vapours) :

Category 2

Median lethal concentration (LC₅₀) 2 mg/L (4 hours) (quoted as 625 ppm) (based on study summary ^{Footnote 3}).

In a non-guideline study, male rats (4/dose) were exposed to 2-mercaptethanol vapour at concentrations of 300, 625, 1,250, 2,500, or 5,000 ppm (0.975, 2.03, 4.06, 8.1, or 16.2 mg/L) (based on study summary ^{Footnote 3}). All animals died at exposures ≥ 1,250 ppm (4.0 mg/L) and 2 died at 625 ppm (2.0 mg/L). The LC₅₀ was determined to be 2 mg/L.

The available data meet the classification criteria for Acute Toxicity (Inhalation) – Category 2 for vapours [HPR 8.1.1(1)].

Acute Toxicity (Inhalation – Dusts and Mists):

No data available

Skin Corrosion / Irritation:

Does not meet criteria

In a Draize study, a 24 hour exposure of undiluted 2-mercaptoethanol to the intact skin of 6 rabbits caused a mean erythema score of 1.8/4 and edema score of 1/4 averaged across all animals at only 24 and 72 hours ^{Footnote 4}. Dilutions of 1:5 (20%) and 1:10 (10%) were not irritating to intact or abraded skin. The scores of this study do not meet the classification criteria. A 4-hour study in 6 rabbits is also available; however, observations were made for only 48 hours ^{Footnote 2Footnote 3}. The average scores across all animals (24 and 48 hours) were 1.5/4 and 1.9/4 for erythema and edema, respectively.

The available data do not meet the classification criteria for Skin Corrosion / Irritation.

Serious Eye Damage / Eye Irritation:

Category 1

In a modified Draize method, 0.1 mL of undiluted 2-Mercaptoethanol was applied to 1 eye of 6 rabbits; the other eye served as a control Footnote 4. In animals exposed to the undiluted test substance, mean 24-, 48-, and 72-hour scores across all animals for corneal opacity, iritis, chemosis, and conjunctival redness were 1/4, 1.33/2, 2.0/3, and 2.33/4, respectively. Two days after treatment with the undiluted material, there was complete hair loss in the periocular area. Scars and opacity of the cornea were apparent 4 months after the treatment in 1 animal. In animals exposed to the 20% solution, 2-mercaptoethanol was not an eye irritant. In a Draize study, application of undiluted 0.1 mL 2-mercaptoethanol to the eye of 6 rabbits resulted in a maximum eye irritation index of 60.1/110, cited as “highly irritating” (based on study summary^{Footnote 3}). In another Draize study (3 rabbits), undiluted 2-mercaptoethanol caused corneal damage that persisted for more than 21 days^{Footnote 2}.

The available data meet the classification criteria for Serious Eye Damage – Category 1 for 2-mercaptoethanol solutions at > 20% concentration [HPR 8.3.2(1)].

Respiratory Sensitization:

No data available

Skin Sensitization:

Category 1A

No human data are available. In a Guinea Pig Maximization Test performed according to OECD TG 406, 2-mercaptoethanol exposure yielded positive results in 8/20 animals (40%) ^{Footnote 5}. Induction was initiated intradermally at a concentration of 0.1% (w/w) with Freund's complete adjuvant and later challenged cutaneously after 12 days with 25% 2-mercaptoethanol.

The available data meet the classification criteria for Skin Sensitization – Category 1A [HPR 8.4.1(4)].

Germ Cell Mutagenicity:

Does not meet criteria

In vivo:  In a mammalian somatic cell study performed according to OECD TG 474, 2-mercaptoethanol was not mutagenic in a mouse micronucleus assay (based on study summary ^{Footnote 3}). Note that this study used intraperitoneal administration.

In vitro: 2-Mercaptoethanol was negative, with and without metabolic activation, in an OECD TG 476 gene mutation study in mouse lymphoma L5178Y cells and in an OECD TG 473 chromosome aberration study in human lymphocytes (based on study summary ^{Footnote 3}).

The available data do not meet the classification criteria for Germ Cell Mutagenicity.

Carcinogenicity :

No data available

No human or animal carcinogenicity studies were identified. 2-Mercaptoethanol has not been reviewed for carcinogenicity by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), or the American Conference of Governmental Industrial Hygienists (ACGIH).

Reproductive Toxicity :

Does not meet criteria

In an OECD TG 422 rat gavage study, doses up to 75 mg/kg had no effect on estrous cycle, mating, or fertility index ^{Footnote 6Footnote 7}.  At 50 and 75 mg/kg, maternal mortality was reported as 20 and 40%, respectively, in combination with a low number of litters produced, statistically significant increases in duration of gestation and post-implantation loss, and a reduction in pup survival. Due to high maternal toxicity, the results of this study do not meet classification criteria. In an OECD TG 414 rat gavage study, administration at doses up to 25 mg/kg showed no evidence of maternal toxicity, embryotoxicity, or teratogenicity ^{Footnote 7}.

The available data do not meet the classification criteria for Reproductive Toxicity.

Specific Target Organ Toxicity – Single Exposure:

Does not meet criteria

Oral Route of Exposure: No human data are available. In rodent studies, central nervous system (CNS) effects have been reported ^{Footnote 4Footnote 8}; however, the doses at which the effects were noted were not disclosed.

Dermal Route of Exposure: No human data are available. Following a single dose of 0.1 mL/kg (corresponding to 112 mg/kg) in rabbits, clinical signs included apathy ^{Footnote 7}.  Necropsy revealed collapse of the lung and congestion of the liver and kidney. This dose is too close to the dermal LD₅₀ to meet classification criteria. At 0.05 mL/kg, apathy and local inflammation were noted but no effects were reported on necropsy.

Inhalation Route of Exposure: No human data are available. CNS effects were noted in rats at atmospheric concentrations close to the LC₅₀ and above ^{Footnote 2}. No effects were described at lower concentrations ^{Footnote 7}.

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

Specific Target Organ Toxicity – Repeated Exposure:

Does not meet criteria

Oral Route of Exposure: In a repeated-dose toxicity study with a reproduction/developmental screening test performed according to OECD TG 422, rats were administered 2-mercaptoethanol at 15, 50, or 75 mg/kg daily by gavage for 7 weeks ^{Footnote 2}. No toxic effects were recorded at 15 mg/kg/day in males or females. In males at doses at and above 50 mg/kg/day, effects noted included salivation, lower body weight gain, minimal to marked vacuolated hepatocytes, lower cholesterol and triglyceride levels, and paleness and accentuated lobular patterns of the liver.  In females at and above 50 mg/kg/day effects noted included salivation, increased liver weight, paleness of liver, slight liver cell hypertrophy, increased incidence and severity of vacuolated hepatocytes, and degenerative cardiomyopathy. Males of the high dose group showed an increased liver weight, minimal to slight hypertrophy of hepatocytes, and degenerative cardiomyopathy. Effects are not serious enough to meet classification criteria and changes in the liver are regarded as adaptive to an increased chemical load. Results do not meet classification criteria.

Dermal Route of Exposure:  No data available

Inhalation Route of Exposure:  No data available

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

Aspiration Hazard:

No data available

No human data are available for 2-mercaptoethanol. This substance is not a liquid hydrocarbon.

Biohazardous Infectious Materials :

Not applicable

2-Mercaptoethanol is not a microorganism, protein or nucleic acid.

Physical hazards

Explosives:

Not evaluated*

* Explosives are excluded from the HPA and and its regulations. Explosives are regulated under the Explosives Act. For more information, visit Natural Resources Canada.

Flammable Gases :

Not applicable

2-Mercaptoethanol 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

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

Gases Under Pressure :

Not applicable

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

Flammable Liquids :

Category 4

2-Mercaptoethanol has a flash point of 67 °C (closed up) (based on study summary ^{Footnote 3}).

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

Flammable Solids :

Not applicable

2-Mercaptoethanol 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

2-Mercaptoethanol has an auto-ignition temperature of 295 °C (based on study summary^{Footnote 3}). Self-Reactive Substances and Mixtures must have a self-accelerating decomposition temperature (SADT) of ≤75 °C to meet the minimum classification in this hazard class.

The available data do not meet the classification criteria for Self-Reactive Substances and Mixtures.

Pyrophoric Liquids :

Does not meet criteria

2-Mercaptoethanol has a flash point of 67°C (based on study summary^{Footnote 3}). Pyrophoric Liquids react at room temperature.

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

Pyrophoric Solids :

Not applicable

2-Mercaptoethanol 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

2-Mercaptoethanol has an auto-ignition temperature of 295 °C (based on study summary ^{Footnote 3}), which is well above the maximum spontaneous ignition temperature of 140 °C for classification.

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

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

Not applicable

2-Mercaptoethanol is soluble in water and forms a stable mixture (based on study summary ^{Footnote 3}) and is, therefore, excluded from classification [HPR 7.12.1(1)].

Oxidizing Liquids:

Not applicable

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.  2-Mercaptoethanol contains oxygen that is chemically bonded only to carbon and hydrogen.

Oxidizing Solids :

Not applicable

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

Organic Peroxides :

Not applicable

2-Mercaptethanol 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 2-mercaptoethanol meets the classification criteria for Corrosive to Metals.

Combustible Dusts :

Not applicable

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

Simple Asphyxiants:

Not applicable

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

Pyrophoric Gases :

Not applicable

2-Mercaptoethanol 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:

2022

Prepared by:

Workplace Hazardous Materials Bureau, Health Canada