Dimethyl ether

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Limited information reported

Data source

Reference

Reference Type:

publication

Title:

Studies of intoxication VI. The action of methyl ether.

Author:

Davidson B

Year:

1925

Bibliographic source:

J. Pharmacol. Exp. Ther., 26:43-48.

Materials and methods

Endpoint addressed:

acute toxicity: inhalation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Human subjects were exposed to 50000, 75000, 82000, 100000, 144000, or 200000 ppm for approximately 60 minutes. Exposures were terminated if unconsciousness occurred. The number of subjects tested in each group was not reported.

GLP compliance:

no

Remarks:

did not exist at the time

Method

Ethical approval:

not specified

Details on study design:

Human subjects were exposed to 50000, 75000, 82000, 100000, 144000, or 200000 ppm for approximately 60 minutes. Exposures were terminated if unconsciousness occurred in the subjects. The number of subjects tested in each group was not reported.
The test substance was prepared by Newth's method and after passing through alcohol, silver nitrate solution, a limetower, and a little strong sulphuric acid, was collected in sulphuric acid and subsequently liberated by the addition of water. After passing through an alkaline solution, it was collected in gas-bags and diluted with air and oxygen to the required concentrations.
Clinical symptoms were noted for all concentrations. Effects on reaction times were tested at all dose levels, memory (writing of the Lord's Prayer) was tested at 82000 and 100000 ppm, muscular coordination (as exemplified by the act of writing) was observed at 82000, 100000, and 144000 ppm, and typewriting was tested at 100000 ppm.

Results and discussion

Results:

In human subjects, 50000 and 75000 ppm of the test substance caused feelings of mild intoxication but no objective symptoms beyond slight lack of attention after 12-minutes exposure to the higher concentration. At 82000 ppm, some incoordination developed after 21.5 minutes, and a complaint was made of indistinct vision. At 100000 ppm, no objective symptoms occurred during the first 15 minutes. Distinct signs of incoordination developed after 21 minutes of exposure. The experiment continued for 64 minutes, with the subject unable to do simple tasks (i.e., balancing of the head required special effort, estimation of time was lost, simple multiplication, and memory were affected). At 144000 ppm, symptoms first occurred after 7 minutes with the subject losing consciousness after 26 minutes. Inhalation of 200000 ppm caused unconsciousness in 17 minutes.

Overall:
Commencing intoxication: 7 min (10% DME), 2 min (14%), 1 min (20%)
Talkativeness: 28 min (10%), 7 min (14%) 5 min (20%)
Noisy talkativeness: 34 min (10%), 20 min (14%), 11 min (10%)
Incoordination and analgesia; 50 min slight (10%), 23 min (14%), 12-14 min (20%)
Unconsciousness: 26 min (14%), 17 min (20%)

Applicant's summary and conclusion

Executive summary:

In human subjects, 50000 and 75000 ppm of the test substance caused feelings of mild intoxication but no objective symptoms beyond slight lack of attention after 12-minutes exposure to the higher concentration. At 82000 ppm, some incoordination developed after 21.5 minutes, and a complaint was made of indistinct vision. At 100000 ppm, no objective symptoms occurred during the first 15 minutes. Distinct signs of incoordination developed after 21 minutes of exposure. The experiment continued for 64 minutes, with the subject unable to do simple tasks (i.e., balancing of the head required special effort, estimation of time was lost, simple multiplication, and memory were affected). At 144000 ppm, symptoms first occurred after 7 minutes with the subject losing consciousness after 26 minutes. Inhalation of 200000 ppm caused unconsciousness in 17 minutes.