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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
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 is sufficient for the purpose of classification and labelling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Principles of method if other than guideline:
Ten male rats were administered 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:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
other: air
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 dose; 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
95% CL:
142 000 - 203 000
Exp. duration:
4 h
Remarks on result:
other: 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)
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.
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 and
Body weight:
Slight 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 sporadic lung noise. All but 1/19 deaths occurred during the exposure.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
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 LC50 of in male ChR-CD® rats is 16.4% (164000 ppm or 309 mg/L) with 95% confidence limits of 14.2 and 20.3%