Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The LD50 values derived from the key-studies were: LD50 (oral, rat) 2900 mg/kg bw and LD50 (dermal, rabbit) 16200 mg/kg bw. The LC50 value (4 h, inhalation, rat) is assumed to be > 20 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 900 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Value:
mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
16 200 mg/kg bw

Additional information

Oral

In an acute oral toxicity study (BASF AG, 1969) listed as key study, groups of young adult rats (10/sex) were given single oral doses of diethyl ketone (99.8 % a.i.) in an aqueous emulsion containing Traganth (concentration in vehicle: 2; 20; 30 %) at doses of 200, 1600, 3200, 4000, 5000 and 6400 µL/kg bw (corresponding to ca. 160, 1300, 2590, 3240, 4050 and 5180 mg/kg bw if calculated with a density of 0.81 g/mL). Animals were observed for 7 days. The oral LD50 value for males and females was calculated to be 2900 mg/kg bw.

In another acute oral toxicity study (Smyth et al., 1954) classified as supporting study, groups of Carworth-Wistar rats were given single oral doses of diluted diethyl ketone. Animals were observed for 14 days. The oral LD50 value in this study was calculated to be 2140 mg/kg bw.

Both studies indicate a LD50 value above the regulatory threshold of 2000 mg/kg bw. The LD50 obtained in the BASF study is regarded as more reliable as the study was performed with more animals per dose and a closer dose spacing than the study by Smyth et al. (1954).

 

Dermal

In an acute dermal toxicity study (Smyth et al., 1954) listed as key study, groups of four male giant albino rabbits were dermally exposed to diethyl ketone. 1/10th of the body surface was treated occlusively for 24 hours. Animals then were observed for 14 days. In the conducted study a LD50 -value of 20 mL/kg bw was identified graphically which corresponds to 16.2 g/kg bw.

In a publication by Nishimura et al. (1994) a LD50 value of 20 g/kg bw is given for diethyl ketone.

Ford et al. (1988) reported that no mortality was noted after application of 5000 mg test substance/kg per rabbit (0/8 deaths) for 24 hours.

 

Inhalation

In an acute inhalation toxicity study (BASF AG, 1969) listed as key study, groups of young adult rats (male/female) were exposed by inhalation to diethyl ketone for 10 min or 35 min (whole body inhalation exposure). Tested concentrations were 123.1 mg/L (10 min exposure) and 112.6 mg/L (35 min exposure). Animals then were observed for 7 days. No mortality was observed in rats exposed to diethyl ketone for 10 min (0/12 animals died). Slight body weight gain was observed. Clinical signs - consisting of irritation of the mucosa and staggering - had reversed within 40 min after exposure. In the 35 min exposure group, one animal died during exposure and one animal immediately after exposure (2/6 animals died). Both animals showed reduced lung dilatation and little arterialized and cyanotic blood. Subsequent to exposure surviving animals showed severe irritation of the mucosa and narcosis. The clinical signs had reversed within 3 days. Slight body weight reduction was noticed for survivors of this group. All surviving animals were sacrificed at the end of the observation period; gross necropsy revealed no anomalies.

In a supporting study (Smyth et al., 1954) groups of 6 male Carworth-Wistar rats were exposed to concentrated diethyl ketone vapours for four hours. 14 days after vapour inhalation mortality was considered as complete. The authors reported only that inhalation of 28.5 mg/m³ (8000 ppm) diethyl ketone resulted in the death of 4/6 animals within 14 days. No further details on test concentrations or results are given.

 

For the structural analogue methyl ethyl ketone an acute LC50 of 35.5 mg/L (11700 ppm) (LaBelle and Brieger, 1955) and 23.5 mg/L (7993 ppm) (Pozzani et al., 1959) were reported for rats after inhalation of the test item for 4 hours and 8 hours, respectively. Also, Smyth et al. (1962) reported that exposure of 6 rats to 8,000 ppm (ca. 23.6 mg/L) methyl ethyl ketone for 8 hours resulted in the death of half of the rats. (For justification of the read-across from MEK see section 13 of the IUCLID.)

 

Based on the data presented above on the acute inhalation toxicity of diethyl ketone and its structural analogue methyl ethyl ketone, it is concluded that the LC50 (4 h) in the rat is above the regulatory threshold for classification and labelling of 20 mg/L for vapours as laid down in Directive 67/548/EEC and Regulation 1272/2008/EC.

References

LaBelle CW and Brieger H (1955). The vapor toxicity of a composite solvent and its principal components. AMAHealth, 12: 623-627.

Pozzani UC, Weil CS, and Carpenter CP (1959). The toxicological basis of threshold limit values: 5. The experimental inhalation of vapor mixtures by rats, with notes upon the relationship between single dose inhalation and single oral dose data. AmHyg Assoc J, 20: 364-369.

Smyth HF Jr, Carpenter CP, et al. (1962). Range-finding toxicity data: List VI. Am Ind Hyg Assoc J 1962, 23: 95-107.

 

Justification for classification or non-classification

Based on the presented results of oral, dermal, and inhalation acute toxicity studies, diethyl ketone is not subject to classification and labelling for acute toxic effects according to Directive 67/548/EEC and Regulation 1272/2008/EC.

In general, the inhalation of vapours of aliphatic ketones can cause reversible central nervous system depression in humans at concentration usually exceeding the threshold for airway-irritation. Therefore, diethyl ketone is classified and labelled according to Directive 67/548/EEC with R67 (vapours may cause drowsiness and dizziness) and according to Regulation 1272/2008/EC with H336 (may cause drowsiness or dizziness).