Registration Dossier

Administrative data

Description of key information

No mortality following 4 hours inhalation exposures as high as 405000 ppm (1907550 mg/m3) in rats or 1 hour exposure as high as 100000 ppm (466000 mg/m3) in rabbits.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: gas
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 70 liters
- Method of holding animals in test chamber: tubes
- Source and rate of air: 20 to 21.9 liters/min
- Temperature, humidity, pressure in air chamber: 20-24 C, humidity 30-70%

TEST ATMOSPHERE
- Brief description of analytical method used: total carbon analyzer
- Samples taken from breathing zone: yes


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
201600 and 405800 ppm
No. of animals per sex per dose:
5
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,organ weights,
Statistics:
None - all animals survived the exposures
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 405 000 ppm
Exp. duration:
4 h
Remarks on result:
other: No lethality at highest concentration tested. Exposure equivalent to 1,907,550 mg/m3.
Remarks:
Equivalent to 1907550 mg/m3.
Mortality:
No mortality observed
Clinical signs:
other: Decreased breathing rates reported for 2 males and 2 females at 201600 ppm and in all animals exposed to 405000 ppm.
Body weight:
No effects on body weight observed.
Gross pathology:
Grey discolored lungs were reported for one male and one female of the group exposed to 201600 ppm and in three male and one female exposed to 405000 ppm.

The discoloration of the lungs may have resulted from the exposure, but the absence of histopathological findings in the subsequent 2-week study at 50000 ppm and the absence of other clinical findings in this study suggest that these observations were of minimal toxicological significance.

Interpretation of results:
GHS criteria not met
Conclusions:
Because mortality did not occur, the 4 hour LC50 value of vapour for the test substance was higher than 405000 ppm (equivalent to 1907550 mg/m3) for both sexes. In addition, immediately after exposure at this high level, signs of narcosis were not seen.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
1 907 550 mg/m³
Quality of whole database:
The study is a guideline study in compliance with GLP.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an OECD 403 guideline study, 10 Sprague Dawley rats (5 males and 5 females) were exposed to 201600 or 405000 ppm (939456 or 1907550 mg/m3) HFO-1234yf in atmosphere for 4 hours. No mortality was observed within 14 days after the exposure. Decreased breathing rates were reported for 2 males and 2 females at 201600 ppm and in all animals exposed to 405000 ppm. The lowest lethal dose (LDLo) was > 405000 ppm (highest exposure level tested) for this study. The LC50 is therefore considered to be > 405000 ppm (equivalent to 1907550 mg/m3).

In another study conducted for the USEPA, 15 males (5/group) and 28 female (6/group presumed pregnant and 5/group 1 and 3) rabbits were exposed to air (Group 1), 50000 ppm (233000 mg/m3; group 2), or 100000 ppm (466000 mg/m3: group 3) for 1 hour. As requested by the USEPA, the presumed pregnant females were exposed on gestation day 12. No signs of toxicity including viability, clinical signs, body weights or histopathology of selected organs were observed at any concentration. The NOAEC was 100000 ppm (highest exposure tested).


Based on results from the developmental toxicity studies, rabbits appear to be more sensitive than rats.

Justification for classification or non-classification

Based on the available information, classification and labelling for acute inhalation toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and its amendments.