Registration Dossier

Administrative data

Description of key information

4h-LC50 = 164000 ppm (309018 mg/m3) air; LOAEL = 84000 ppm (158277 mg/m3) air

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.
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
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

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
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.
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%

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
309 018 mg/m³
Quality of whole database:
Available data show consistent results; conclusions fulfil the quality criteria (validity, reliability, repeatability).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Predominant acute effect of inhalational exposure to high concentrations of DME is anaesthesia. Narcotic effects have been reported in humans at an atmospheric concentration of 120000 ppm.

The substance has low inhalation toxicity (lethality) with a rat 4-hour LC50 value of 164000 ppm. During inhalation to substance concentrations of 84000 ppm acute toxicity was observed in the form of ataxia, anaesthesia in 2 hours, short jerky respirations and lung noise (post exposure).During inhalation to ≥ 121000 ppm acute toxicity was observed in the form of ataxia, anaesthesia in 15-30 minutes, heavy respiration, coma and lung noise (post exposure).

 

This substance is a gas, and tests to evaluate dermal and oral systemic toxicity were not feasible.


Justification for selection of acute toxicity – oral endpoint
Study technically not feasible because the test substance is a gas.

Justification for selection of acute toxicity – inhalation endpoint
Most appropriately performed study to assess LC50.

Justification for selection of acute toxicity – dermal endpoint
Study technically not feasible because the test substance is a gas.

Justification for classification or non-classification

Based on the rat 4-hour LC50 of 164000 ppm (309018 mg/m3), anesthetic and clinical effects after 2 hours of exposure to 84000 ppm (158277 mg/m3), and the minimal startle response effects at 20000 ppm (37685 mg/m3) in the developmental study, the substance does not need to be classified for acute toxicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.