Hazardous Substance Assessment - Acetone

Important Note: Hazardous Substance Assessments are technical documents that have been produced by Health Canada as educational and information resources for suppliers of hazardous products under the Hazardous Products Act and Regulations. For more information on supplier roles and responsibilities, visit Supplier Responsibilities.

Identification

Chemical Name: 

Acetone

CAS #:

67-64-1

Chemical Composition:

(CH3)2CO

Synonyms:

2-Propanone; Propanone.

UN #:

1090 [Flammable liquid]

Pictogram(s):

Figure 1.

Flammable Liquids
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, and/or
  • skin sensitization.

Figure 2.

Negative health effects
Figure 2 - Text Description

The symbol within the pictogram is a flame with a line underneath it. This symbol indicates that hazardous products with this pictogram can ignite easily and burn rapidly if they are not stored and handled properly.

WHMIS Classification

Health Hazards:

Serious Eye Damage / Eye Irritation: Category 2A

Physical Hazards:

Flammable Liquids: Category 2

Health Hazards

Acute Toxicity (Oral):

Does not meet criteria

LD­50: 5,800 mg/kg (rat, female) Footnote 1.

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

Acute Toxicity (Dermal):

Does not meet criteria

LD­50: > 15,800 mg/kg (rabbit) Footnote 2.

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

Acute Toxicity (Inhalation – Gas):

No data available

Acute Toxicity (Inhalation – Vapour):

Does not meet criteria

LC50: 76 mg/L (4 hr) (based on study summary Footnote 3).

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

Acute Toxicity (Inhalation – Dust and Mist):

No data available

Skin Corrosion / Irritation:

Does not meet criteria

In a Smyth & Carpenter study, 10 µl of Acetone was applied to the clipped skin of 5 rabbits Footnote 2. The exposure lasted for 24 hours and the observations were scored using the Smyth and Carpenter system. A grade 1 out of 10 was obtained, which indicates the absence of skin irritation. In another rabbit skin irritation study, Acetone scored 0.67 for erythema and 0 for edema, again concluding that the chemical is not irritating Footnote 4.

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

Serious Eye Damage / Eye Irritation:

Category 2A

In an Organisation for Economic Co-operation and Development Test Guideline (OECD TG) 405 study, undiluted Acetone (0.1 mL) was instilled into the eyes of 4 rabbits Footnote 5. Observations were recorded at 24, 48, and 72 hours for all eye parameters and mean scores were calculated for each of the 4 rabbits. The scores were as follows for each parameter: 2, 1.67, 2 and 2 for corneal opacity (resolved by day 10); 1.33, 1.0, 1.33 and 1.33 for iritis (resolved by day 14); 3, 2.67, 2.67 and 3 for conjunctival redness (resolved by day 21); and 3, 2.0, 2.67 and 2.33 for chemosis (resolved by day 10). According to HPR 8.3.2(3), these results meet the criteria for a Category 2A classification.

Other studies were available to further support this classification. In a Draize test, 0.1 mL of undiluted Acetone was instilled into an eye of 4-to-6 rabbits and resulted in a maximum average score (MAS) of 66/110 at 24 hours post-instillation Footnote 6. The modified MAS for undiluted Acetone was determined to be 65.75. These two values indicate that Acetone is an irritant. In a Smyth study, an irritation grade for undiluted Acetone was established on the Carpenter scale Footnote 7. From the results, Acetone fell into the grade 5 category, indicating that 0.02 mL of Acetone yields an irritation score of over 5.0 (indicating severe injury to the eye) whereas 0.005 mL does not. In another study, Acetone (neat) was found to be a severe irritant in the Bovine Corneal Opacity/Permeability (BCOP) in vitro assay, which followed OECD TG 437 Footnote 8. In a rabbit eye irritation study, 0.1 mL of Acetone caused 6/6 positive reactions for cornea opacity, iritis and conjunctiva redness Footnote 9. These effects were completely reversible.

In another study, dilutions of Acetone in polyethylene glycol (1%, 3%, 10% and 30%) resulted in mild eye irritation with scores of 1/110, 4/110, 3/110, and 6/110 respectively Footnote 10. Polyethylene glycol is a solvent that does not meet criteria for eye irritation and the study itself is well conducted. Thus, from this study it can be concluded that solutions of Acetone below 30% do not meet criteria for a Category 2A classification. 

The available data meet the classification criteria for Eye Irritation – Category 2A for Acetone solutions above 30% [HPR 8.3.2(3)].

Respiratory Sensitization:

No data available

Skin Sensitization:

Does not meet criteria

Negative results were obtained when testing Acetone in a Guinea Pig Maximisation Test (GPMT) Footnote 3,Footnote 11. In fact, Acetone is often used as vehicle for the GPMT Footnote 12. Acetone was also tested for skin sensitization in mice using an ear sensitization assay. This study also reported with negative results Footnote 13.

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

Germ Cell Mutagenicity:

Does not meet criteria

In vivo: Negative results were obtained in a micronucleus assay in normochromatic peripheral blood erythrocytes of B6C3F1 mice (based on study summary Footnote 3). These mice received a subchronic oral exposure to Acetone in drinking water at doses up to 2 mg/kg. No indication of clastogenic activity was observed. Acetone also showed no genotoxic activity in an in vivo micronucleus assay in Chinese hamster bone marrow cells (based on study summary Footnote 3).

In vitro: In a Salmonella typhimurium reverse mutation assay, results were negative both with and without metabolic activation Footnote 3,Footnote 14,Footnote 15. A chromosome aberration assay in CHO cells and a mouse lymphoma L5178Y cell assay without metabolic activation were also negative (based on study summary Footnote 3).

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

Carcinogenicity:

Does not meet criteria

The American Conference of Governmental Industrial Hygienists (ACGIH) has classified Acetone as A4 – Not classifiable as a human carcinogen Footnote 16. Acetone is often used as a negative control or vehicle in dermal carcinogenicity studies (based on study summary Footnote 3). There are no indications of an elevated tumor incidence in Acetone-treated vehicle control groups. Acetone has not been reviewed by the International Agency for Research on Cancer (IARC) or the National Toxicology Program (NTP).  

The available data do not meet the classification criteria for Carcinogenicity.

Reproductive Toxicity:

Does not meet criteria

For the most part, reproductive studies testing Acetone had negative results. Acetone exposure (5,000 mg/L drinking water for 8 weeks or 10,000 mg/L drinking water for 4 weeks) had no adverse effect on male fertility in rats (based on summary study Footnote 3). In another rat study, there were no adverse effects noted on male fertility after 6 weeks of exposure to 0.5% Acetone in drinking water (based on summary study Footnote 3). Acetone also showed no reproductive toxicity in male or female mice up to dosages of 5,000 and 11,000 mg/kg bw/day (based on summary study Footnote 3). Exposure of pregnant rats to 0, 440, 2,200, or 11,000 ppm Acetone aerosol did not result in developmental toxicity or teratogenicity. Maternal toxicity (decreased body and uterine weight) was evident at the high dose, with a significant decrease of fetal weight. In another study, 6,600 ppm by aerosol resulted in maternal toxicity (increased liver weights) and developmental toxicity (reduction of fetal weights and a slight increase in late resorptions) (based on summary study Footnote 3). Another study was available that found no reproductive effects when pregnant rats inhaled up to 26.2 mg Acetone/16 hours/day at days 6-19 of gestation Footnote 13. Parameters included the number of implantations, the mean percent of live pups / litter, the mean percent of resorptions/litter, sex ratio, and the incidence of fetal malformations or variations.

Positive results were seen in two studies. Developmental toxicity was observed at 15.7 mg/L in mice that inhaled 0, 1, 5.2, or 15.7 mg/L Acetone for 6 hours/days during the days 6-17 of gestation Footnote 13. Reduced fetal weight and a slight increase in incidence of late resorptions were seen; however, no teratogenic effects were noted. In another study, mice receiving 3,500 mg/kg/day Acetone by gavage on days 6-16 of gestation, the number of females producing viable litters was reduced (44.4% vs. 94.4% in controls). The survival of pups and the birth weight were decreased. The concentrations at which adverse effects were seen are above the threshold for classification.

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: Groups of 6 male rats (young adults and older adults) were administered Acetone to generate acute toxicity data and to note the approximate dose inducing the first observable signs of toxic action Footnote 17. A dose of 5 mL/kg (3,949 mg/kg) gave the first observable gross signs of toxicity. In another study, groups of at least 5 female rats were dosed with 5,370 – 6,980 mg/kg Acetone Footnote 1. Observations that indicated signs of toxicity were made and recorded at specified times: frequently on the day of dosing, and daily thereafter for 14 days. Clinical signs of toxicity appeared within 3 hours of dosing. Severe toxicity was generally characterized by prostration and death that occurred in 24 – 72 hours. Recovery was observed beginning at 72 hours. In both cases, the toxicity seems to be generalized rather than targeting a specific organ.

Dermal Route of Exposure:

No data available

Inhalation Route of Exposure: Twenty-two male and female volunteers were exposed for 4 hours to Acetone at a concentration of 250 ppm and were described as having some mild neurobehavioral changes (when tested by auditory tone discrimination and a mood test) Footnote 18. These effects are too small for classification and no significant effects were observed in the other 5 neurobehavioural tests. Acetone produced slight irritation at 300 ppm, while 500 ppm irritated the eyes and respiratory system but was still tolerable Footnote 19. A 3 h exposure of inhaled Acetone up to 25,300 ppm caused prolonged CNS depression in rats Footnote 20.  At concentrations up to 23.1 g/m3 (or 23.1 mg/L), inhaled Acetone vapour caused reduced motor activity in rats; at 60.7 g/m3 Acetone caused convulsions, narcosis and death Footnote 21. Although in adverse effects are seen in these studies, they are only present at dosages above the threshold for classification.

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: Acetone was mildly toxic to rats and mice when administered in drinking water for 13 weeks Footnote 22,Footnote 23. Minimal toxic doses were estimated to be 20,000 ppm Acetone (1,700 mg/kg) for male rats and male mice and 50,000 ppm Acetone (3,400 mg/kg) for female mice. No toxic effects were identified for female rats. The testis, kidney, and hematopoietic system were identified as target organs in male rats, and the liver was the target organ for male and female mice. Kidney effects, renal tubule degeneration were noted in a 90 day study at very high oral doses in rats (500 and 2,500 mg/kg) Footnote 24. The doses at which effects are seen are above the threshold for classification.

Dermal Route of Exposure: Lifetime dermal exposure to low doses of Acetone (20 to 160 mg Acetone/mouse) with 2 or 3 treatments per week (up to 573 days) caused no noticeable effects on survival or incidence of skin neoplasms (based on study summary Footnote 3). No other endpoints were examined. Additionally, due to the volatility of Acetone, standard conditions of dermal application will result in considerable evaporation from the skin surface lowering the effective dose for dermal uptake.

Inhalation Route of Exposure: After 8 weeks of exposing rats to 19,000 ppm (3 hrs/day), there were no indications of adverse systemic toxic effects from the investigated endpoints (based on study summary Footnote 3). Neurobehavioral examination of 71 workers with 14 years mean duration of exposure to Acetone (exposures ranged from 416-890 ppm) indicated statistically significant deficits in nerve conduction test results (indicative of neuropathy); however, the author noted that these abnormalities do not always reflect functional neurological impairment Footnote 25. Exposed workers also reported eye, skin and upper respiratory symptoms (no statistical analysis was provided).

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

Aspiration Toxicity:

Does not meet criteria

Acetone was given orally at a dose of 1mL/kg to 8 anesthetized rats (4 of each sex) Footnote 26. The oral administration technique enabled aspiration of Acetone into the lungs to study Acetone aspiration toxicity. All 8 rats died; however, only 2/8 rats showed severe lung haemorrhage and were considered to have died from aspiration of Acetone. Acetone was found to evaporate too quickly to be aspirated; however, if ingested very quickly it can be aspirated into the lungs and cause severe lung haemorrhage. Since no human data are available and Acetone is not a liquid hydrocarbon, these results are not applicable to the classification of Acetone as an Aspiration Toxicant.

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

Biohazardous Infectious Materials:

Not applicable

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

Physical Hazards

Explosives:

Not Evaluated*

* Explosives are excluded from the Hazardous Products Act and Regulations. Explosives are regulated under the Explosives Act. For more information, visit Natural Resources Canada.

Flammable Gases:

Not applicable

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

Flammable Aerosols:

No data available

No data are available to determine whether Acetone meets the classification criteria for Flammable Aerosols.

Oxidizing Gases:

Not applicable

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

Gases Under Pressure:

Not applicable

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

Flammable Liquids:

Category 2

Acetone is a liquid with an initial boiling point of 56.2°C and a flashpoint (closed cup) of -18°C Footnote 27.

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

Flammable Solids:

Not applicable

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

Self-Reactive Substances and Mixtures:

No data available

No data are available to determine whether Acetone meets the classification criteria for Self-Reactive Substances and Mixtures.

Pyrophoric Liquids:

Does not meet criteria

Acetone has an auto-ignition temperature of 465 °C and will not ignite at room temperature Footnote 28.

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

Pyrophoric Solids:

Not applicable

Acetone 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

Acetone has an auto-ignition temperature of 465 °C, which is well above the spontaneous ignition temperature for classification Footnote 28.

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 Gasses:

Not applicable

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

Oxidizing Liquids:

Not applicable

Section 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 and hydrogen.  Acetone contains oxygen chemically bonded to carbon.

Oxidizing Solids:

Not applicable

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

Organic Peroxides:

Not applicable

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

Corrosive to Metals:

Does not meet criteria

Acetone is not corrosive to the common metals at room temperature Footnote 29.

The available data do not meet the classification criteria for Corrosive to Metals.

Combustible Dusts:

Not applicable

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

Simple Asphyxiants:

Not applicable

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

Pyrophoric Gases:

Not applicable

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

Regulatory and Other Information

Regulatory Information:

Hazardous Substance Assessments are prepared by Health Canada as educational and information resources. Under the Hazardous Products Act (HPA), suppliers of hazardous products must, upon the sale or importation of a hazardous product, provide a Safety Data Sheet that meets the requirements set out in the Hazardous Products Regulations (HPR).  For more information, see the Technical Guidance on the Requirements of the Hazardous Products Act (HPA) and the Hazardous Products Regulations (HPR) – WHMIS 2015 Supplier Requirements.

Other Information:

The information and classifications contained in these Hazardous Substance Assessments are based on publically 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:

2020

Prepared By:

Workplace Hazardous Materials Bureau, Health Canada

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