Registration Dossier

Administrative data

Description of key information

In accordance to REACH Annex XI Section 2; information requirement section 8.5.1, guideline testing for acute oral toxicity and acute dermal toxicity is technically not feasible because the test substance is a gas.
In a K2 acute inhalation study, the substance had very low acute inhalation toxicity with no deaths in rats exposed for four hours to 663000 ppm. Therefore, a 4-hour LC50 of > 663000 ppm in male rats was reported. Anesthetic effects occurred at 186000 ppm but in the absence of oxygen supplementation, anesthetic or CNS effects would be driven by oxygen deprivation, not direct substance effects.

Key value for chemical safety assessment

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:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Remarks:
Used males only, number tested at each concentration was 6.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: ChR-CD®
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 238 - 285 g
- Fasting period before study: not reported
- Housing: rats were housed in suspended stainless-steel, wire mesh cages
- Diet : Purina Certified Rodent Chow® #5O02 ad libitum)
- Water: ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Chamber temperature never exceeded 27°C during any exposure.
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported
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 apparatus: 20 L glass exposure chamber
- Exposure chamber volume: 20 L
- Method of holding animals in test chamber: not reported
- Source and rate of air: 10 L/min.
- Method of conditioning air: not reported
- System of generating test atmosphere: Atmospheres of the test material were generated by metering the test gas through a single stage regulator and a Brooks R6-15A flowmeter. The gas passed through Teflon® lines into a mixing flask (500 mL , 3-neck, round bottom). Metered dilution air and oxygen were added at the mixing flask. The stream entered the 20 L glass exposure chamber directly through the top. Total flow was 10 L/min.


TEST ATMOSPHERE
- Brief description of analytical method used: Gas standards and samples were analyzed using a Wilks Scientific Miran I infrared analyzer at a wavelength of 8.75 microns. Standards were prepared daily by quantitative dilutions of the gas in calibrated gas bottles. Gas samples were taken at 15-minute intervals using a Tekmar gas tight syringe. Chamber concentrations were determined by comparison with a standard curve. A mean and standard deviation were calculated for each exposure. Chamber temperature and oxygen were also monitored throughout each exposure.
- Samples taken from breathing zone: not reported


VEHICLE
- Composition of vehicle (if applicable): air

Chamber temperature never exceeded 27°C during any exposure.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Mean Measured concentrations: 18900, 186000 and 663000 ppm
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: observed daily (excluding weekends)
- Frequency of weighing: weighed daily (excluding weekends)
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs and body weight
Sex:
male
Dose descriptor:
LC50
Effect level:
> 663 000 ppm
Exp. duration:
4 h
Remarks on result:
other: Anesthetic effects occurred at 186000 ppm.
Mortality:
No mortality at any concentration
Clinical signs:
other: 18900 ppm - Exposure: no signs; Post-Exposure: None 186000 ppm - Exposure: Reduced response to sound; Post-Exposure: None 633000 ppm - Exposure: No response to sound, gasping, labored breathing, sluggishness and compulsive gnawing on basket (1 a
Body weight:
18900 ppm - Slight weight loss 24-48 hrs post-exposure

633000 ppm - Slight weight loss 24 hours post-exposure
Gross pathology:
not examined
Interpretation of results:
other: ALC is greater than 663000 ppm
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
ALC > 663000 ppm

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

Groups of 8 week old ChR-CD® male albino rats were exposed to the test substance gas in air for single 4-hr periods. The ALC of the test substance gas is greater than 663000 ppm, the maximum concentration generated. Clinical signs observed during exposure included reduced response to sound, gasping, labored breathing, sluggishness, and compulsive gnawing on basket. Mild weight loss was observed 24-48 hrs post exposure but normal weight gain was achieved thereafter.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 898 434 mg/m³

Additional information

In a K2 acute inhalation study, the substance had very low acute inhalation toxicity with no deaths in rats exposed for four hours to 663000 ppm. Therefore, a 4-hour LC50 of > 663000 ppm (1898434 mg/m3) in male rats was reported. Anesthetic effects occurred at 186000 ppm.

Justification for classification or non-classification

In a K2 acute inhalation study, the substance had very low acute inhalation toxicity with no deaths in rats exposed for four hours to 663000 ppm. Therefore, a 4-hour LC50 of > 663000 ppm in male rats was reported. Based on this study, no classification is required for the acute inhalation endpoint, according to the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

 

Data lacking due to waiving arguments, so substance cannot be classified for acute oral or dermal toxicity according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.