Hazardous substance assessment – EDTA tetrasodium salt

Important note: Hazardous substance assessments are technical documents produced by Health Canada as educational and informational 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 both the former and amended Hazardous Products Regulations (HPR). Learn more about the HPR amendments and transition period.

Identification

Chemical name:

(Ethylenedinitrilo) tetraacetic acid (EDTA) tetrasodium salt

CAS #:

64-02-8

Chemical composition:

C10H16N2O8Na4 (anhydrous); C10H16N2Na4O84H20 (tetrahydrate)

Synonyms:

Acetic acid, (ethylenedinitrilo)tetra-, tetrasodium salt; Glycine, N,N'-1,2-ethanediylbis(N-(carboxymethyl)-, sodium salt (1:4); Glycine, N,N'-1,2-ethanediylbis(N-(carboxymethyl)-, tetrasodium salt; Sodium EDTA; Sodium ededate; Tetrasodium ethylenediaminetetraacetate.

UN #:

Not available

Pictogram(s):

Figure 1.
Figure 1. Text version below.
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:

EDTA tetrasodium salt does not meet the criteria for classification.

Health hazards

Acute Toxicity (Oral):

Category 4

Median lethal dose (LD50) (rat): 1,658 mg/kg.

In a study conducted similarly to the Organisation for Economic Co-operation and Development Test Guideline (OECD TG) 401, the LD50 was 1,658 mg/kg (based on study summary Footnote 1). The study was conducted on 5 Wistar rats per sex per dose by oral gavage. The doses used were 1,210, 1,780, 2,610 and 3,830 mg/kg by weight. Observations were made daily for a period of 14 days. The LD50 of 1,658 mg/kg falls within the HPR range outlined for Acute Toxicity (Oral) Category 4, > 300 mg/kg to ≤ to 2,000 mg/kg [HPR 8.1.1(1)].

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

Acute Toxicity (Dermal):

No data available

Acute Toxicity (Inhalation – Gases):

Not applicable

EDTA tetrasodium salt 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

Acute Toxicity (Inhalation – Dusts and Mists):

No data available

Skin Corrosion / Irritation:

Does not meet criteria

No human data are available. Multiple studies are available on skin irritation reporting EDTA tetrasodium salt to be not irritating Footnote 2. In a study conducted according to OECD TG 404, 0.5 g of an 80% aqueous preparation of EDTA tetrasodium salt was applied under an occlusive patch to the skin of 3 rabbits for 4 hours Footnote 2. No edema was noted. An average score (24-48-72 hours) for erythema was reported to be 0.43/4. Results of this study do not meet classification criteria for Skin Irritation. In another study, application of 0.5 g of a 40% aqueous solution of EDTA tetrasodium salt to the skin of 3 rabbits for 4 hours under occlusive conditions also did not elicit any skin reactions Footnote 2.

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

Serious Eye Damage / Eye Irritation:

Category 2A

No human data are available. In an eye irritation study performed similarly to OECD TG 405, the instillation of 0.1 mL of a 40% aqueous solution of EDTA tetrasodium salt to the eyes of 3 rabbits resulted in average scores (24-48-72 hours) of 1/2 for iritis, 2.56/3 for conjunctival redness and 2.33/4 for chemosis Footnote 2. These results meet the classification criteria for Eye Irritation – Category 2 [HPR 8.3.2(3)]. Since no observations were made after 72 hours, reversibility could not be determined for sub-classification. There are other studies available that were performed before relevant OECD TG were established and used 50 mg (standard amount is 100 mg) of the test substance in 2 rabbits and reported an average corneal score (24-72 hours) of ≥1 in 2/2 rabbits (based on study summary Footnote 1). The effects were not fully reversible within 8 days.

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

Respiratory Sensitization:

Does not meet criteria

Nasal provocation tests were conducted on 28 workers with occupational asthma and/or rhinitis Footnote 3. These workers were previously exposed to the disodium (CAS # 139-33-3) and/or the tetrasodium salt of EDTA. They were either exposed to the disodium salt alone or to both salts, in detergents or disinfectants and, in one case, in an air freshener. At concentrations of 1, 2 and 4% of EDTA tetrasodium salt in aqueous solution, 6, 3 and 1 workers were tested. All 10 workers tested positive for sensitization Footnote 3. Due to the absence of supportive evidence of sensitization from exposure to EDTA and its salts, these data do not meet classification criteria.

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

Skin Sensitization:

Does not meet criteria

A 78-year-old woman with recurrent leg ulcers had mild stasis dermatitis Footnote 2Footnote 4. After applying a paste containing EDTA tetrasodium salt, a weeping dermatitis spread to her legs, arms and face. She yielded a positive response on 2 occasions in a patch test to a 1% aqueous solution of EDTA tetrasodium salt and petrolatum. Due to the widespread use of EDTA and its salts and limited reports of skin sensitization in the literature (only 1 potential case found for EDTA tetrasodium salt), the prevalence of cases is insufficient to meet classification criteria.

No animal data are available on EDTA tetrasodium salt. Negative results were obtained for a read-across chemical (EDTA disodium salt, CAS # 139-33-3) in a guinea pig maximization test (based on study summary Footnote 1).

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

Germ Cell Mutagenicity:

No data available

No in vivo data are available for EDTA tetrasodium salt. A read-across chemical, disodium EDTA, CAS # 139-33-3, tested negative for mutagenicity in a micronucleus test and in a dominant lethal assay when administered orally in mice (based on study summary Footnote 2).

No in vitro data are available for EDTA tetrasodium salt. Studies for read-across chemicals disodium EDTA, CAS # 139-33-3 and trisodium EDTA, CAS # 150-38-9, were negative in bacterial and mammalian cell gene mutation assays performed with and without S9 activation (based on study summary Footnote 1).

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

Carcinogenicity:

Does not meet criteria

EDTA tetrasodium salt 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).

Negative results were obtained with a read-across chemical, trisodium EDTA (CAS # 150-38-9) Footnote 5.

Reproductive Toxicity:

Does not meet criteria

In a well-conducted developmental toxicity study, pregnant rats were orally exposed to an equimolar dose of EDTA tetrasodium salt based on 1,000 mg/kg of EDTA (actual dose of 1,374 mg/kg of EDTA tetrasodium salt) by gastric intubation from gestational days 7-14 Footnote 6. There was no effect on litter size or sex ratio. The mortality index (post-implantation loss) and developmental abnormalities were comparable among pups of EDTA tetrasodium salt-treated dams and the control dams. No substance-related statistically significant increase in malformations was observed in the treated animals. Maternal toxicity was evident with diarrhea in 90% of the dams and reduced weight gain during mid gestation.

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: An OECD TG 401 study was conducted in rats (10 per sex per dose) gavaged with 1210, 1780, 2000 or 2610 mg/kg EDTA tetrasodium salt. The LD50 was 1780 mg/kg in females. Clinical signs of toxicity at 1780 mg/kg and higher included dyspnea, apathy, ataxia, shaggy fur and poor general state as well as redness and/or bloody ulceration of the glandular part of the stomach, redness of the mucous membrane and general hyperemia (based on study summary Footnote 1).

In another OECD TG 401 study conducted in rats (5 per sex per dose) gavaged with 1210, 1780, 2610 or 3830 mg/kg EDTA tetrasodium salt, the LD50 was reported as 1658 mg/kg with clinical signs of dyspnea, apathy, shaggy fur and poor general state as well as stomach pathology of atonic, redness of the mucous membrane and general hyperemia (based on study summary Footnote 1).

The effects described in the study summaries occur at or above the LD50 and therefore could be due to the onset of death. These effects do not meet the criteria of this hazard class.

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 – Single Exposure.

Specific Target Organ Toxicity – Repeated Exposure:

Does not meet criteria

Oral Route of Exposure: No data are available for EDTA, tetrasodium salt. Negative results were obtained for read-across chemicals such as the disodium salt of EDTA, CAS # 139-33-3 Footnote 7 and the tri sodium salt of EDTA, CAS # 150-38-9 Footnote 5, in chronic and sub-chronic studies.

Dermal Route of Exposure: No data available

Inhalation Route of Exposure: No data are available for EDTA, tetrasodium salt. Negative results were obtained in 2 studies, a 28-day and a 90-day study, on a structurally similar substance, Trilon BD (EDTA disodium salt, CAS # 139-33-3) (based on study summary Footnote 1).

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 EDTA tetrasodium salt. This substance is not a liquid hydrocarbon.

Biohazardous Infectious Materials:

Not applicable

EDTA tetrasodium salt 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

EDTA tetrasodium salt 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

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

Gases Under Pressure:

Not applicable

EDTA tetrasodium salt is not a gas. The classification criteria for Gases under Pressure do not apply to this substance.

Flammable Liquids:

Not applicable

EDTA tetrasodium salt is not a liquid. The classification criteria for Flammable Liquids do not apply to this substance.

Flammable Solids:

Does not meet criteria

EDTA tetrasodium salt is a non-flammable solid Footnote 2.

The available data do not meet classification criteria for Flammable Solids.

Self-reactive Substances and Mixtures:

Does not meet criteria

EDTA tetrasodium salt has a melting point of 300°C Footnote 8. 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:

Not applicable

EDTA tetrasodium salt is not a liquid. The classification criteria for Pyrophoric Liquids do not apply to this substance.

Pyrophoric Solids:

Does not meet criteria

EDTA tetrasodium salt does not ignite on contact with air (based on study summary Footnote 1).

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

Self-heating Substances and Mixtures:

Does not meet criteria

EDTA tetrasodium salt has an auto-ignition temperature greater than 200°C (based on study summary Footnote 1), which is well above the temperature at which spontaneous ignition would need to occur for classification (HPR 7.11.1(2)).

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:

Does not meet criteria

Flammable gases are not produced by EDTA tetrasodium salt upon contact with water (based on study summary Footnote 1).

The available data do not meet the classification criteria for Substances and Mixtures Which, in Contact with Water, Emit Flammable Gases.

Oxidizing Liquids:

Not applicable

EDTA tetrasodium salt is not a liquid. The classification criteria for Oxidizing Liquids do not apply to this substance.

Oxidizing Solids:

Does not meet criteria

EDTA tetrasodium salt is incapable of reacting exothermically with combustible materials given its chemical structure, in which the oxygen is only bonded to carbon and is therefore excluded from the criteria of this hazard class (HPR 7.14.1(1)) Footnote 2.

The available data do not meet the classification criteria for Oxidizing Solids.

Organic Peroxides:

Not applicable

EDTA tetrasodium salt 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 EDTA tetrasodium salt meets the classification criteria for corrosiveness to metals; however, the substance is used widely in electroplating Footnote 2.

Combustible Dusts:

Does not meet criteria

EDTA tetrasodium salt is not readily combustible and does not contribute to fire through friction (based on study summary Footnote 1). The French National Research and Safety Institute for the Prevention of Occupational Accidents and Diseases (INRS) states that under certain conditions, the dust of EDTA tetrasodium salt can form explosive mixtures with air; however, due to the lack of available studies, this substance cannot be classified as a combustible dust Footnote 9.

The available data do not meet the classification criteria for Combustible Dusts.

Simple Asphyxiants:

Not applicable

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

Pyrophoric Gases:

Not applicable

EDTA tetrasodium salt 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

References

Footnote 1

European Chemicals Agency (2019) Tetrasodium ethylenediaminetetraacetate - REACH dossier. Available at: https://www.echa.europa.eu/.

Return to footnote 1 referrer

Footnote 2

European Chemicals Bureau (2004) Tetrasodium ethylenediaminetetraacetate (Na4EDTA). CAS No.: 64-02-8. 51. European Communities.

Return to footnote 2 referrer

Footnote 3

Laborde-Casterot, H., et al (2012) Occupational rhinitis and asthma due to EDTA-containing detergents or disinfectants. Am.J.Ind.Med. 55(8; http://dx.doi.org/10.1002/ajim.22036):677-682.

Return to footnote 3 referrer

Footnote 4

de Groot, A. C. (1986) Contact allergy to EDTA in a topical corticosteroid preparation. Contact Derm. 15(4):250-252.

Return to footnote 4 referrer

Footnote 5

National Toxicology Program (1977) Bioassay of trisodium ethylenediaminetetraacetate trihydrate (EDTA) for possible carcinogenicity. NCI-CG-TR-11; 77-811. National Institute of Health, Bethesda, Maryland.

Return to footnote 5 referrer

Footnote 6

Schardein, J. L., Sakowski, R., Petrere, J. and Humphrey, R. R. (1981) Teratogenesis studies with EDTA and its salts in rats. Toxicology & Applied Pharmacology 61423-428.

Return to footnote 6 referrer

Footnote 7

CCOHS (2015) CHEMINFO Database. Available at: http://ccinfoweb.ccohs.ca/.

Return to footnote 7 referrer

Footnote 8

Rumble, J.(2019) CRC Handbook of Chemistry and Physics. 100 Edition. J. Rumble (Eds.). CRC Press, Boca Raton, FL.

Return to footnote 8 referrer

Footnote 9

INRS (2019) EDTA et sel t�trasodique. Available at: http://www.inrs.fr/publications/bdd/fichetox/fiche.html?refINRS=FICHETOX_276&section=incendieExplosion.

Return to footnote 9 referrer

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