Hazardous substance assessment- Methyldiethanolamine

Important note: Hazardous substance assessments are technical documents produced by Health Canada as educational and information resources for suppliers of hazardous products under the Hazardous Products Act (HPA) and its regulations. For more information on supplier roles and responsibilities, visit supplier responsibilities.

This hazardous substance assessment was conducted according to the former and amended Hazardous Products Regulations (HPR). Learn more about the HPR amendments and transition period.

Identification

Chemical name:

Methyldiethanolamine (MDEA)

CAS #:

105-59-9

Chemical composition:

CH3N(CH2CH2OH)2

Synonyms:

MDEA; 2,2'-(Methylimino)diethanol; 2-(N-2-Hydroxyethyl-N-methylamino)ethanol; Bis(2-hydroxyethyl) methyl amine; Bis(2-hydroxyethyl)methylamine; 2,2'-Methyliminodiethanol; Ethanol, 2,2'-(methylimino)bis-; Ethanol, 2,2'-(methylimino)di-; N-Methyldiethanolamine.

UN #:

Not Available

Pictogram(s):

Figure 1.
Skin irritation / Sensitization Eye irritation
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

WHMIS classification

Health hazards:

Acute Toxicity (Oral) - Category 4

Eye Irritation - Category 2A

Physical hazards:

MDEA does not meet the criteria for classification.

Health hazards

Acute Toxicity (Oral):

Category 4

Median lethal dose (LD50): 1,945 mg/kg (rat)Footnote 1.

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

LD50: 6,230 mg/kg (rabbit) Footnote 2.

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

Acute Toxicity (Inhalation - Gases):

Not applicable

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

Acute Toxicity (Inhalation - Vapours):

Does not meet criteria

Exposure to the saturated vapour concentration of MDEA for 6 hours did not produce any mortalities or significant signs of toxicity in Sprague-Dawley rats Footnote 1.

The available data do not meet the classification criteria for Acute Toxicity (Inhalation - Vapours).

Acute Toxicity (Inhalation - Dusts and Mists):

No data available

Skin Corrosion / Irritation:

Does not meet criteria

A volume of 0.5 mL undiluted MDEA was applied to the shaven dorsal trunk skin of New Zealand White rabbits and held in contact for 4 hours by an occlusive dressing Footnote 1. The contact site was inspected for local signs of injury and inflammation after removal of the occlusive dressing. Erythema and edema were scored based upon the 5-point Draize system.

The results showed that MDEA produced very mild effects, the mean 24-, 48- and 72-hour score across all animals for erythema being 0.2/4 and for edema 0.2/4.

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

Serious Eye Damage / Eye Irritation:

Category 2A

MDEA was shown to be an eye irritant after 4/10 rabbits sustained eye injury post exposure in a range-finding test looking at the degree of corneal necrosis from various volumes and concentrations of chemicals Footnote 2. In a study conducted equivalently to the Organisation for Economic Co-operation and Development Test Guideline (OECD TG) 405, 2 rabbits scored post-exposure averages (24-, 48-, and 72-hour) of 1 for corneal opacity, 0 for iritis, 1.7 for conjunctival erythema, and 0.7 for chemosis; redness, swelling, and clouding of the cornea as well as conjunctival bleeding were also observed Footnote 3. The effects of the substance on the eye disappeared after 8 days. The original BASF grading was converted into the numerical grading according to the Draize test.

The available data meet the classification criteria for Eye Irritation - Category 2A [HPR 8.3.2(3)].

Respiratory Sensitization:

No data available

Skin Sensitization:

Does not meet criteria

Only 1 positive human patch test was observed in 229 patients (atopy not discussed) who worked with fluids containing the substance Footnote 4. Results were negative in a Magnusson-Kligman guinea pig maximization test (GPMT) Footnote 5.

The available data do not meet the classification criteria for Skin Sensitization.

Germ Cell Mutagenicity:

Does not meet criteria

In Vivo: Results were negative in an OECD TG 474 (Mammalian Erythrocyte Micronucleus Test) study in mice Footnote 3.

In Vitro: Results were negative in multiple OECD guideline studies, including studies conducted according to OECD Guideline 471 (Bacterial Reverse Mutation Assay) in Salmonella typhimurium tester strains TA98, TA100, TA1535, TA1537, and TA1538, both with and without metabolic activation Footnote 3,Footnote 6Footnote 7; OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test) in Chinese hamster ovary (CHO) cells, both with and without metabolic activation Footnote 3; and OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells) in CHO cells, both with and without metabolic activation Footnote 3,Footnote 8.

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

Carcinogenicity:

No data available

MDEA has not been reviewed by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), or the American Conference of Governmental Industrial Hygienists (ACGIH).

No carcinogenicity studies were identified.

Reproductive Toxicity:

Does not meet criteria

Animals: In an OECD TG 421 (Reproduction / Developmental Toxicity Screening Test) good laboratory practice (GLP)-compliant study, rats (10/sex/dose) were gavaged with 0, 100, 300, or 1,000 mg/kg/day MDEA Footnote 9,Footnote 3. At 1000 mg/kg/day, the body weight in parental males and females was reduced; however, there were no adverse effects on fertility of either sex, with the gestation index at 100% in all groups. There was increased post-implantation loss in the high dose group (1,000 mg/kg/day), and the rate of delivered pups was reduced within this group. However, the live birth index was not changed, with the difference in number of stillborn pups not considered statistically significant between the groups. No adverse effects were noted in the low- and mid-dose groups. Results for reproductive toxicity were also negative in a dermal OECD Guideline 414 (Prenatal Developmental Toxicity) study Footnote 3.

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 an acute toxicity study in rats with limited details available, rats gavaged with 1,945 mg/kg of undiluted MDEA showed signs of sluggishness, lacrimation, chromodacryorrhea, diarrhea, kyphosis and prostration Footnote 1. Survivors usually recovered from effects between 2 and 3 days after dosing. Necropsy of animals that died revealed distended stomachs containing blood with dark red or purple discolouration of the glandular portion. Survivors had no gross pathology at necropsy. While the above effects are seen at a concentration of MDEA within the guidance value range for Category 2 of this hazard class, the concentration is also the LD50 for MDEA. This makes it difficult to distinguish the effects of a single dose exposure from the overall acute toxic effects.

Dermal Route of Exposure: No human data are available. In an acute study in rats exposed to unspecified doses of MDEA for 24 hours under occlusive conditions, the LD50 was reported to be 10,244 mg/kg in males and 11,336 mg/kg in females. Clinical signs of sluggishness, unsteady gait, emaciation, and prostration were observed Footnote 1. Survivors usually recovered from effects between 3 and 5 days after dosing. At necropsy, the majority of animals that had survived the study did not reveal any gross pathology, but a few showed red mottled lungs and dark red livers. Insufficient study details are available for doses at which effects occur to use for classification.

Inhalation Route of Exposure: No human data are available. In an acute lethality study in rats at the saturated vapour concentration of MDEA, a 6-hour exposure caused no mortalities and no significant signs of toxicity Footnote 1.

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: No data available.

Dermal Route of Exposure: No human data are available. No systemic toxicity was observed in rats in a 13-week study performed according to OECD TG 411 Footnote 3. A short-term repeated-dose study in rats with nine occlusive applications over a period of 11 days was also negative Footnote 3.

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 MDEA. This substance is not a liquid hydrocarbon.

Biohazardous Infectious Materials:

Not applicable

MDEA is not a microorganism, nucleic acid or protein.

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

MDEA 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

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

Gases Under Pressure:

Not applicable

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

Flammable Liquids:

Does not meet criteria

MDEA is a liquid with a flash point of 138 ºC (closed cup) Footnote 3.

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

Flammable Solids:

Not applicable

MDEA 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

MDEA is a tertiary amine with an auto-flammability temperature of 280 °C at 1013 hPa, determined by the EU method A.15 (DIN 51794)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

MDEA is a liquid with a flash point of 138 ºC (closed cup) Footnote 3. Pyrophoric liquids react at room temperature.

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

Pyrophoric Solids:

Not applicable

MDEA 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

MDEA has an auto-flammability temperature of 280 °C at 1013 hPa, determined by the EU method A.15 (DIN 51794) 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

MDEA is a tertiary amine that does not contain metals or metalloids 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. MDEA is a tertiary amine that contains oxygen chemically bonded only to carbon and hydrogen.

Oxidizing Solids:

Not applicable

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

Organic Peroxides:

Not applicable

MDEA 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 MDEA meets the classification criteria for Corrosive to Metals.

Combustible Dusts:

Not applicable

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

Simple Asphyxiants:

Not applicable

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

Pyrophoric Gases:

Not applicable

MDEA 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 label and safety data sheet 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

References

Footnote 1

Ballantyne, B. and Leung, H. W. (1996) Acute toxicity and primary irritancy of alkylalkanolamines. Veterinary and Human Toxicology 38:6:422-426.

Return to footnote 1 referrer

Footnote 2

Smyth, H. F., Jr. et al (1954) Range-finding toxicity data: List V. Archives of Industrial Hygiene and Occupational Medicine 10:61-68.

Return to footnote 2 referrer

Footnote 3

European Chemicals Agency (2018) 2,2'-Methyliminodiethanol - REACH dossier. Available at: http://www.echa.europa.eu/

Return to footnote 3 referrer

Footnote 4

Geier, J. et al (2003) Patch testing with components of water-based metalworking fluids. Contact Dermatitis 49:85-90.

Return to footnote 4 referrer

Footnote 5

Leung, H. W. and Blaszcak, D. L. (1998) The skin sensitization potential of four alkylalkanolamines. Veterinary and Human Toxicology 40:2:65-67.

Return to footnote 5 referrer

Footnote 6

Zeiger, E. et al (1987) Salmonella mutagenicity tests III. Results from the testing of 255 chemicals. Environmental Mutagenesis 9: Supplement 9:1-110.

Return to footnote 6 referrer

Footnote 7

National Toxicology Program (1983) Salmonella mutagenesis test results EMIC/51200. NTP Technical Bulletin. 9, 5-6.

Return to footnote 7 referrer

Footnote 8

Leung, H. W. and Ballantyne, B. (1997) Evaluation of the genotoxic potential of alkylalkanolamines. Mutation Research 393:1-2:7-15.

Return to footnote 8 referrer

Footnote 9

BASF (2010) Results of a Reproduction/Developmental Toxicity Screening Test in Wistar Rats With 2,2'-(Methylimino)Diethanol (CAS NO. 105-59-9). EPA/OTS Doc #: 88-100000197.

Return to footnote 9 referrer

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