Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14/03/2016 - 26/05/2016
Reliability:
1 (reliable without restriction)

Data source

Reference
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Test material form:
gas: vapour

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
Route and Method:
Inhalation exposure (nose-only inhalation exposure) was selected as dosing route to assess the safety of the test substance when it will be exposed to human by inhalation. The rats individually held in the restraining tubes for nose-only inhalation exposure (Muenster Ltd.) were subjected to nose-only inhalation exposure using a flow-past nose-only inhalation exposure chamber (hereinafter abbreviated as “chamber”, Muenster Ltd.) according to the method widely used in the similar study. The chamber is constructed from a stackable tier, which has 16 exposure ports per tier. A single-tier chamber was used in this study.
The flow rate of air-supply to the chamber was set at 16 L/min. The flow rate of the chamber exhaust was set at 14 L/min, which was approximately 10% lower than the air supply, because the inner pressure of the chamber has to be positive to ensure a reliable exposure.

Exposure duration and frequency:
Inhalation exposure was conducted once for 4 hours in accordance with the guideline applied to this study.

Dose setting:
The information has not been obtained regarding acute inhalation toxicity of the test substance. The definition to the vapor in the guideline is applied to the test substance based on the property. In this study, the test condition to gas in the guideline was applied to assess safety in a high concentration level. Target exposure concentration for the first exposure was set at 2500 ppm to be able to terminate the test using small number of animals when the toxicity of the test substance was relatively low. The exposure was carried out according to the procedure described in Appendix 1. Depending on the number of humanely killed or dead animals, the test procedure followed the indicated arrows until a categorization could be made.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Analysis by Gas Chromatography
Duration of exposure:
ca. 4 h
Concentrations:
The exposure concentrations were 13.82 and 115.77 mg/L (2,590 and 21,690 ppm respectively: target nominal concentrations of 2,500 and 20,000 ppm).
The coefficient variations of the exposure concentrations throughout the exposure were
1.2% and 1.1%. These results met the criterion for temporal concentration stability,
which was set at 10% or below.
The nominal concentrations were 14.41 and 124.26 mg/L.
No. of animals per sex per dose:
3
Control animals:
no
Statistics:
None performed.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
13.82 mg/L air (analytical)
Based on:
test mat.
Mortality:
In the 115.77 mg/L group, all males and 2 females died by the end of exposure.
Clinical signs:
other: Decrease in locomotor activity and coma were observed in 1 female of the 115.77 mg/L group at the end of exposure. These symptoms disappeared on day 2. No abnormalities or deaths were observed in the males or females of the 13.82 mg/L group.
Body weight:
Decrease of body weight on day 2 was noted in 1 female of the 13.82 mg/L group and 1 female of the 115.77 mg/L group. All animals regained weight by day 4, and thereafter all animals showed body weight gain until the end of the observation period.
Gross pathology:
There were no abnormalities in the dead animals or animals subjected to the necropsy after the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LDC50 for the test substance is determined to be 13.82 < LC50 < 115.77 mg/L.
Executive summary:

Acute inhalation toxicity of HCFO-1233yd(E/Z) was evaluated by exposing it to Crl:CD(SD) rats by nose-only inhalation exposure once for 4 hours.


The exposure concentrations were 13.82 mg/L and 115.77 mg/L.


In the results of exposure at 115.77 mg/L, 5 rats, which were 3 males and 2 females, died by the end of 4 hours exposure. Exposure to this concentration resulted in a severe decrease in locomotor activity and coma on the remaining female. On day 2, these symptoms disappeared. No dead animals or abnormalities were observed by exposure at 13.82 mg/L. Since the decrease body weight in the 13.82 mg/L group was slight and no clinical signs were noted, it was concluded that the body weight change was attributable to the exposure procedure, such as holding in the restraint tube. No gross abnormalities were observed in the necropsy on the dead animals or animals on the end of the observation period.