Acetone

Endpoint summary

Description of key information

LD50 oral: rat 5800 mg/kg
LD50 dermal: guinea pig, rabbit  at least 7400 mg/kg
LC50 inhalation: rat 3 hr 132000 mg/m3; rat 4 hr  76000 mg/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 800 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

76 000 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

7 400 mg/kg bw

Additional information

Acute oral toxicity

The oral LD₅₀ of acetone was 5800 mg/kg bw in female rats (Key study: Freeman and Hayes, 1985). In a further reliable study, the LD₅₀ value in young adult male and female rats was 7190 mg/kg bw (Supporting study: Kimura et al., 1971).

Acute dermal toxicity

There is no key study available for acute dermal exposure. Two reliable studies, which were not performed according to important criteria of today standard methods, can be used in a weight of evidence approach as these studies indicate that the acute dermal toxicity of acetone is low and would not lead to classification.After application of a minimum of three dosages on the clipped intact or abraded skin of groups of 4 male guinea pigs or on the abraded skin of groups of 4 male or female rabbits under an occlusive dressing, the dermal LD₅₀ was found to be higher than 9.4 mL acetone/kg bw (ca. 7,400 mg/kg bw) in both species (Roudabush et al., 1965). With a dermal LD₅₀ of more than 20 mL/kg (ca. 15,700 mg/kg) acetone was practically non-toxic to male New Zealand rabbits during a 24-hour occlusive exposure (Smyth et al., 1962).

Acute inhalation toxicity

There is no key study available for acute inhalation exposure. Two reliable studies, which were not performed according to important criteria of today standard methods, can be used in a weight of evidence approach as these studies indicate that the acute inhalation toxicity of acetone is low and would not lead to classification. The 3-hr LC₅₀ in male Sprague-Dawley rats was calculated with a value of 132 mg/L air (55,700 ppm) acetone for whole-body exposure. The critical effect leading to death is CNS depression and narcosis (Bruckner and Peterson, 1981). In this study the duration of exposure was shorter than the standard 4 hr exposure. Within 3 hrs of exposure no mortalities were observed up to a concentration of 60 mg/L. Based on additional tests for CNS depression by measuring impairment of unconditioned performance and reflexes, an approximately linear time-response relationship for depressive effects was observed up to 3 hrs exposure to 30 to 60 mg/L. If the performance scores of these depressive effects are extrapolated to a 4 hr exposure period, there are no indications that prolongation of exposure to 4 hrs will lead to CNS depressive effects causing death in the concentration range of 30 to 45 mg/L. Consequently, the 4-hr LC₅₀ value is expected to be above the value of 20 mg/L, the critical value for classification according to EU regulation 1272/2008.

A study from 1959, applying an old technology of vapor generation with whole-body exposure of groups of 6 female Carworth rats in 9 -L desiccator chambers, reported a 4-h LC₅₀ value of 76.0 mg/L air (no analytical verification of concentrations and no further observations reported) (Pozzani et al., 1959). This study confirms the relative low acute inhalation toxicity of acetone resulting in no classification. Acute exposure via inhalation was shown to induce sensory irritation in humans and in mice (for details see Section 7.9.3).

Human experience

The experience with human cases of intoxication (for details see Section 7.10.3) confirms the low acute toxicity of acetone (Overviews to be found in: American Chemistry Council Acetone Panel, 2003; Morgott, 2001; OECD, 1999; WHO, 1998). For the development of any overt signs of toxicity in humans, accidental exposures to extremely large amounts of acetone by inhalation of vapour or ingestion of liquid are necessary (e.g. several thousand ppm of acetone vapour, or ingestion resulting in acetone blood levels up to several thousand mg/L). Respiratory tract irritation is the most sensitive indicator of acetone overexposure. The most noticeable systemic effect is a generalized central nervous system depression. No cases of fatality are known and acetone has a low potential for causing chronic or delayed health effects. The doses at which these effects are seen is well above the OEL or the STEL values.

A high dose of acetone (ca. 10 g/kg bw) was rapidly eliminated by an infant (9 kg bw) with clinical signs and neurological symptoms returning to normal within 4 days after intoxication and without neurodevelopmental sequelae (Gamis and Wassermann, 1988).

After a 6-hr exposure of human volunteers to acetone the LOAEL for significant effects as experience of sensory irritation of the nose, eyes, throat and trachea, and changes of hematological parameters was 500 ppm or 1190 mg/m³, the NOAEL was 250 ppm or 594 mg/m³ (Matsushita et al., 1969a) (for details see Section 7.10.5).

Justification for classification or non-classification

Oral toxicity: no classification according to EU regulation 1272/2008 as LD₅₀ from key study is distinctly above the critical value of 2000 mg/kg

Dermal toxicity: no classification according to EU regulation 1272/2008 is to be expected as based on weight of evidence approach and on oral LD₅₀, the dermal LD₅₀ is distinctly above the critical value of 2000 mg/kg

Inhalation toxicity: no classification according to EU regulation 1272/2008 based on the LC₅₀ resulting from a weight of evidence approach: the 4 hr LC₅₀ is distinctly above the critical value of 20,000 mg/m³ for acetone vapors.

Labelling: R67, Vapours may cause drowsiness and dizziness.