Registration Dossier

Administrative data

Description of key information

Oral, LD50 = 1200 - 1700 mg/kg bw, rat (Kimura)

Oral, LD50 = 3560 mg/kg bw, rat (Smyth)

Inhalation, LD50 = 97 mg/L, rat, male, 4h (Smyth)

Inhalation, LC50 = 133 mg/L, mouse, 3h (Molitor)

Inhalation, LD50 = 180/200 mg/L, mouse, male/female, 90 min (Kobayashi)

Inhalation, LD50 = 95/98 mg/L, mouse, male/female, 90 min (Kobayashi)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
1 200 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
97 000 mg/m³

Additional information

Oral

The study by Kimura (1971) is considered to be more reliable than Smyth (1962), based on the greater quantity of information reported on the study, and that it is in effect conducted in triplicate (if the age differences between the test animals ignored). The age dependent differences in sensitivity observed in the rat acute toxicity were also observed in inhalation toxicities in mice (Kobayashi, 1985). Both studies indicated greater tolerance of diethyl ether in young animals. The lowest LD50, for adult rats at 1200 mg/kg bw, is selected as the most conservative value and is carried forward for risk assessment and classification and labelling.

Inhalation

The available data on LT50 (lethal time) is not relevant to the acute toxicity endpoint, but does indicate concentrations which are definitively lethal in the test animal. Older studies for which little experimental information is available are discarded (Klimisch 4). Of the available literature studies for which more information is available (Smyth (1962), Molitor (1936), Kobayashi (1985)), all are in approximate agreement. As a result the longest exposure data (4h) in the rat is taken as a conservative value (LC50 = 97 mg/L) and is taken forward for risk assessment and classification and labelling.

Dermal

Acute toxicity data via the dermal route is not considered necessary as inhalation is the most likely route of exposure due to the high vapour pressure of diethyl ether. Any dermal exposure is likely to be reduced by rapid vapourisation from the skin. Supplied as supporting information, one dermal study reported an LD50 >20 mL/kg bw, the maximum application rate.

Other routes

The toxicity data obtained via other routes was of low quality and not considered relevant to risk assessment or classification and labelling.

The available acute toxicity data is considered to be complete and adequate for risk assessment and classification and labelling, based on a weight-of-evidence approach, according to Regulation (EC) No. 1907/2006, Annex XI, section 1.2.

Justification for classification or non-classification

Directive 67/548/EEC

The oral rat LD50 lies in the range 200 - 2000 mg/kg bw, qualifying for classification as R22. The rat inhalation LC50 lies far above the 20 mg/L/4h upper limit for R20. According to Directive 67/548/EEC, Annex VI, 3.2.3, the substance is classified as R22 Harmful if swallowed. In addition, based on the well known and documented experience in humans of the narcotic effects of diethyl ether, and taking into account it's historical use as an anesthetic, and including it's harmonised Community classification according to Annex I, according to Annex VI, 3.2.8, the substance is classified as R67 Vapours may cause drowsiness and dizziness.

Regulation (EC) No. 1272/2008

The oral rat LD50 lies in the range 300 - 2000 mg/kg bw, qualifying for classification for Acute Oral Toxicity, Category 4. The inhalation rat LC50 lies far above the 20 mg/L/4h upper limit for Acute Inhalation Toxicity.

In addition, based on the known human and animal narcotic effects, the substance is classified for Specific Target Organ Toxicity, single exposure, Category 3, according to Regulation (EC) No. 1272/2008, Annex I, 3.8.2.2.2.