Dimethyl ether

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Sep - 4 Oct 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was selected as the key study because the information provided for the hazard endpoint includes information at concentrations above the limit for classification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

only males were used

Principles of method if other than guideline:

Ten male rats were exposed to the test substance for a 4-hour exposure period at concentrations of 84000, 121000, 152000, 169000, or 205000 ppm. Clinical signs and body weights were evaluated during the 14-day recovery period. Necropsies were performed on surviving rats after the 14-day recovery period.

GLP compliance:

not specified

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl ether

EC Number:

204-065-8

EC Name:

Dimethyl ether

Cas Number:

115-10-6

Molecular formula:

C2H6O

IUPAC Name:

dimethyl ether

Details on test material:

- Physical state: DME is a gas which was received as a liquid under pressure
- Purity: 99.9%

Test animals

Species:

rat

Strain:

other: albino ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 204-301 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: rats were kept for a 10d quarantine period prior to selection for the test

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Remark on MMAD/GSD:

Not applicable as DME is a gas.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 20 L glass exposure chamber.
- Method of holding animals in test chamber: chamber volume was kept as small as was practical, handling of rats was minimized
- Atmosphere generation: Atmospheres were generated by means of a single stage regulator through a flow meter (with a stainless steel float) directly into the top of a 20-L glass exposure chamber. Dilution air flowing through a flow meter (with a stainless steel float) joined the DME stream at the top of the chamber. The air/DME flow was maintained at 10 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: GC

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

8.4; 12.1; 15.2; 16.9; 20.5% (84000; 121000; 152000; 169000; 205000 ppm)

No. of animals per sex per dose:

10 males per concentration; 2 males per cage

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

probit analysis

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

164 000 ppm

Based on:

test mat.

95% CL:

142 000 - 203 000

Exp. duration:

4 h

Mortality:

Mortality of 0/10, 3/10, 2/10, 7/10, and 7/10 occurred in the 84000, 121000, 152000, 169000, and 205000 ppm groups, respectively. All but one death (205000 ppm) occurred during the exposures.
84000 ppm: ataxia, anesthesia in 2 hours, shallow respiration, lung noise (post exposure); >84000 ppm: ataxia, anesthesia in 15-30 min, heavy respiration, coma, lung noise (post exposure)

Clinical signs:

other: Clinical observations for the 4 highest test concentration groups were similar. Anesthesia was achieved more rapidly at the higher concentrations. Observations were: ataxia, unresponsiveness to noise, anesthesia in 15 to 30 min with heavy respirations

Body weight:

Slight body weight loss 1-2 days post-exposure in the 4 highest test concentration groups

Other findings:

Post-exposure survivors rapidly awoke and showed no clinical signs, other than transient weight loss for 1-2 days and sporadic lung noise. All but 1/19 deaths occurred during the exposure.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

4-hour LC50 = 164000 ppm
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Executive summary:

A 4-hour whole-body inhalation LC50 study was conducted in male ChR-CD® rats. During exposure, the rats demonstrated ataxia, anesthesia, coma, and death. Post-exposure, survivors rapidly awoke and showed no clinical signs other than transient weight loss for 1-2 days and sporadic lung noise. All but 1/19 deaths occurred during the exposures. The 4-h LC50 in male ChR-CD® rats is 16.4% (164000 ppm or 309 mg/L) with 95% confidence limits of 14.2 and 20.3%.