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Diss Factsheets

Administrative data

Description of key information

Oral: In accordance to REACH Annex XI Section 2; information requirement section 8.5.1, guideline testing for acute oral toxicity is technically not feasible because the test substance is a gas.
Dermal: In accordance to REACH Annex XI Section 2; information requirement section 8.5.3, guideline testing for acute dermal toxicity is technically not feasible because the test substance is a gas.
Inhalation: OECD 403. 4-hr LC50, rat. The LC50 was 2072 ppm (14069 mg/m3). Reliability =2.

Key value for chemical safety assessment

Acute toxicity: via inhalation route

Link to relevant study records
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
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 labeling and/or risk assessment.
according to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
The study was conducted according to the guideline in effect at the time of study conduct.
GLP compliance:
Test type:
standard acute method
Limit test:
Crj: CD(SD)
Details on test animals or test system and environmental conditions:
- Age at study initiation: Five weeks
- Weight at study initiation: 160-200 grams (males); 133-166 grams (females)
- Fasting period before study: no
- Housing: polycarbonate cages lined with hard wood chips bedding; 2 or 3 of the same sex per cage throughtout quarantine and acclimation; housed individually in wire mesh cage during the study.
- Diet (e.g. ad libitum): pellet; ad libitum
- Water (e.g. ad libitum): filtered tap water irridated with UV ad libitum except during exposure.
- Acclimation period: from day of animal delivery to day administration started.

- Temperature (°C): 21.5°- 22.8°C
- Humidity (%): 50.5%- 60.7%
- Air changes (per hr): 6-20/hour
- Photoperiod (hrs dark / hrs light): 12-hr from 7:00 to 19:00 throughout entire experimental period including quarantine and acclimation, excluding exposure.

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Details on inhalation exposure:
- Exposure apparatus: stainless steel, rectangular parallel piped shaped whole body inhalation chamber.
- Exposure chamber volume: approximately 95 L inner volume
- Method of holding animals in test chamber: whole body
- Source and rate of air: metered gas mixed with pressurized air at flow rate of 20 L/min to make target concentration.
- Method of conditioning air: prepared gas continuously supplied to inhalation chamber from front.
- System of generating particulates/aerosols: test substance gas supplied in a gas-cylinder metered to the appropriate volume for each concentration level with a mass-flow-controller after reducing its pressure to 0.2 MPa. Metered gas was mixed with pressurized air at a flow rate of 20 L/min in order to make target concentration. For exposure atmosphere, prepared gas was continuously supplied to inhalation chamber from its front. Part of the exhausted gas was introduced to a hydrocarbon meter then the temporal variation of the exposure concentration was monitored.
- Treatment of exhaust air: exposure atmosphere continuously exhausted from porous plate at backside of chamber.
- Temperature, humidity, pressure in air chamber: 23.0-24.5°C, 45-58%, pressure not reported, oxygen concentration 21%

- Brief description of analytical method used: Part of the exposure atmosphere into the chamber was collected with a vacuum pump and gas-tight syringe at approximately 30 min, 2 and 3.5 hours after the commencement of the exposure. Gas chromatograph with a flame ionization detector (FID/GC).
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
417, 1199, 1759, 2441, and 3578 ppm (targeted concentrations of 880, 1250, 1770, 2500, and 3540 ppm, respectively).
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: on admin day, observations conducted at 1,2 and 3 hours after commencement of exposure, immediately after end of exposure , and 1 and 2 hours after exposure; thereafter observed once a day for 14 days (until day 15).
- Frequency of Weighing: Days 1,2,4,8 and 15
- Necropsy of survivors performed: yes
The fifty-percent lethal concentration was calculated by the Van der Waerden method from the actual exposure concentration obtained from GC/MS analysis and the lethality at the termination of observation on Day 15.
Preliminary study:
A dose-finding study was conducted with the targeted concentration of 880, 2500, and 3540 ppm using three males and three females each for exposure level. All males and females of the 3540 ppm group; two males and two females of the 2500 ppm group died. There were no dead animals in the 880 group. The LC50 was estimated at around 2500 ppm. Target concentrations of study were set at 880, 1250, 1770, 2500, and 3540 ppm.
Dose descriptor:
Effect level:
2 072 ppm
All males and females of the 2500 and 3450 ppm groups died by Day 6 (Day 1 was designated as the exposure day). No mortality was observed at ≤ 1770 ppm.
Clinical signs:
other: During exposure, a decrease in locomotor activity was observed in males and females at 2500 and 3450 ppm from 2 hours after commencement of exposure. Salivation was observed in males and females at 3450 three hours after the commencement of exposure. Post
Body weight:
Body weight of the dead animals (≥2500 ppm) decreased until the day of their death. The body weight of the females of the 1770 ppm group were suppressed on Day 2. All other animals gained weight during the observation period.
Gross pathology:
Dark reddish lungs, edema and/or atrophy of the thymus and spleen were observed in the animals found dead. There were no abnormalities in the animals subjected to the necropsy on Day 15.
Interpretation of results:
not classified
Migrated information Criteria used for interpretation of results: expert judgment
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
LC50 = 2072 ppm.
Executive summary:

Groups of 5 male and 5 female Crj:CD®(SD)IGS rats were exposed whole-body for four hours to concentrations of 417, 1199, 1759, 2441, and 3578 ppm (conversion temperature; 23.2° to 24.1°C) of the test substance for the targeted concentrations of 880, 1250, 1770, 2500, and 3540 ppm respectively. All males and females of 2500 ppm and 3540 ppm groups died due to the exposure of the test substance. Almost all of these animals died on the administraion day or one day after adminitration after revealing a decrease in locomotor activity. Dark reddish change and oedema of the lung were observed in the dead animals. It was considered that the animals died due to respiratory lesion due to the exposure. It was also suggested that the test substance had irritability to mucous membrane, because nasal discharge in all exposure groups and salivation in the groups exposed to concentration of 2500 ppm or higher were observed in the clinical observations. Atrophy of thymus and spleen that was observed in one dead female was considered as a non-specific finding by general prostration, as the animal that died on Day 6. It was concluded that the test substance causes irritability to mucous membranes, and the concentration of 2500 ppm or higher causes fatal respiratory lesions. The LC50 was 2072 ppm for both males and females.

Endpoint conclusion
Dose descriptor:
14 069 mg/m³ air

Additional information

In a rat 4-hour acute inhalation study, the LC50 was 2072 ppm (14069 mg/m3). It was suggested that the test substance was irritating to the mucous membrane due to nasal discharge observed in all exposure groups and salivation in rats exposed to ≥2500 ppm (16975 mg/m3).

Justification for classification or non-classification

Based on the rat 4-hour LC50 of 2072 ppm (14069 mg/m3) and resulting respiratory irritation an acute inhalation Cat 3 and STOT SE 3 are warranted according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, and Xn; R20 (harmful by inhalation) according to EU Directive 67/548/EEC.

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