Hazardous substance assessment - Acetone

Identification

Chemical name:

Acetone

CAS #:

67-64-1

Chemical composition:

(CH₃)₂CO

Synonyms:

2-Propanone; Propanone.

UN #:

1090 [Flammable liquid]

Pictogram(s):

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

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:

Eye Irritation: Category 2A

Specific Target Organ Toxicity – Single Exposure: Category 3 (Narcotic Effects)

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 a category of 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 a category of Acute Toxicity (Dermal).

Acute Toxicity (Inhalation – Gases):

Not applicable

Acetone 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

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

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

Acute Toxicity (Inhalation – Dusts and Mists):

No data available

No data are available to determine whether acetone meets the classification criteria for a category of Acute Toxicity (Inhalation – Dusts and Mists).

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 2 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

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

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 2 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:

Category 3 (Narcotic Effects)

Oral Route of Exposure: In humans, it was reported that there were up to 1 500 incidents of acetone poisoning in the US between 1988 and 1997, mostly due to ingestion of pure acetone. About 30% of the incidents required treatment and no fatalities occurred. Exposure to extremely large amounts of acetone by ingestion of a liquid is necessary, specifically ingestion resulting in acetone blood concentrations that are up to several thousand mg/L, for signs of toxicity to be observed. Acetone toxicity in humans is characterized by non-specific local and systemic effects. The most noticeable systemic effect is a generalized central nervous system depression, which can range from light-headedness to narcosis, depending on the magnitude and length of the exposure. Mild functional renal insufficiency was occasionally reported in cases of acetone-induced narcosis ^Footnote 3.

In cases of accidental ingestion of liquid acetone, fatigue, irritability, dizziness, and breathing irregularities may occur. When the poisoning is severe, these symptoms may precede the development of gastrointestinal disturbances and a temporary loss of consciousness. While many cases of severe acetone poisoning have been reported in the literature, no deaths have been recorded ^Footnote 17.

Dermal Route of Exposure: No data available

Inhalation Route of Exposure: In respect of neurological effects that follow inhalation or oral exposures to acetone, the Agency for Toxic Substances and Disease Registry (ATSDR) concluded that: "Based on evidence from human and animal studies, acetone is associated with neurological effects ranging from mild neurobehavioral effects to severe narcosis." ^Footnote 18

In 1 study, a group of male participants was exposed to an acetone concentration between 21 049 and 84 194 ppm for 1 to 8 hours. Signs of narcosis were seen at a concentration of 21 049 ppm and higher within 3 to 6 hours ^Footnote 18,^Footnote 19.

In an occupational study, 8 male workers exposed for 2 minutes or for 4 hours on a single day to a concentration of 12 000 ppm of acetone reported throat and lung irritation but also narcotic effects such as unconsciousness, dizziness, unsteadiness, confusion and headache ^Footnote 18,^Footnote 20.

Another occupational study involving 9 workers exposed to a concentration of 1 006 ppm of acetone reported signs of headache and light-headedness in some of the participants ^Footnote 21.

Male and female volunteers (n=22) were exposed for 4 hours to acetone at a concentration of 250 ppm and were described as exhibiting some mild neurobehavioural changes as determined by auditory tone discrimination and a mood test ^Footnote 22. The effects observed in this study are mild and do not meet classification criteria.

Acetone-exposed employees (n=71) and controls (n=86) participated in a study on neurotoxicity. The employees worked at a coin-printing factory. Acetone exposure levels over an 8-hour shift ranged from 988 to 2 114 mg/m3. Acetone-exposed employees reported an elevated percentage of certain symptoms, including memory difficulties (15%), sleep disturbances (32%), headache (42%) and hand and feet numbness (26%). The percentage of controls reporting these symptoms was lower (8%, 5.8%, 18%, and 5.8%, respectively) ^Footnote 23.

Acetone-exposed employees (n=110) and controls (n=67) participated in a study on acetone-related health effects. The employees worked at an acetate fiber plant. Acetone exposure levels measured at the end of a work shift were 19.6 to 1 018 ppm in breathing-zone air. Symptoms reported by the acetone-exposed employees to have occurred in the previous 6 months for which there was a reasonable exposure-response relationship included a heavy, vague or faint feeling in the head and nausea ^Footnote 24.

Students (n=25), separated into 5 groups, were exposed to a concentration of 0, 100, 250, 500 or 1 000 ppm of acetone. The groups at an exposure concentration of 250 ppm and above reported general weakness, heavy eyes, and a lack of energy, among other effects ^Footnote 25.

Acetone exposure under controlled laboratory conditions produced slight irritation in volunteers at a concentration of 300 ppm, while at 500 ppm exposure irritated the eyes and respiratory system but was still tolerable ^Footnote 26.

The narcotic effects reported in humans from inhalation studies are sufficient to meet classification criteria for Specific Target Organ Toxicity – Single Exposure – Category 3 [HPR 8.8.1(1)].

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 27,Footnote 28}. 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 29. 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 23. 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 30. 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 HPA. 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:

Not evaluated

Classification of a hazardous product in the Flammable Aerosols or Aerosols hazard class is product dependent.

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 31.

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 a category of 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 32.

The available data do not meet the classification criteria for a category of 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 32.

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 Gasses:

Excluded from classification

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:

Excluded from classification

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 31.

The available data do not meet the classification criteria for a category of 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.

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