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Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19/05/2015 - 21/07/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
Reason for selection of test animal: This strain of rat was selected because rats are generally used in toxicity studies and the test facility has experience of using this strain of rats.
Number and age of animals received:4 females aged 7 weeks (for the 3rd group); 7 females aged 8 weeks ( for the 1st and 2nd groups)
Standard body weight range at shipment: Females aged 7 weeks, 140 to 210 g; females aged 8 weeks, 160 to 230 g
Body weight range at receipt: Females aged 7 weeks, 155 to 167 g; females aged 8 weeks, 190 to 207 g
Age at administration: 8 to 9 weeks
Number of groups: 2
Number of animals per group: 3
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Preparation method: A required amount of the test article was accurately weighed out into a measuring glass, to which the vehicle was added to the prescribed concentration. The mixture in the measuring glass was stirred with a stirrer to dissolve the test article.
Preparation frequency: Immediately before use Dosing solution was placed in light-resistant and airtight
Storage conditions: container, and was not stored.
Precautions in preparation: The test article was handled in a clean bench, and prepared using protective equipment including masks and gloves to avoid inhalation and contact to the eyes, skin and clothing.
Remaining dosing solutions: The remaining dosing solutions were collected as industrial waste for incineration.
Doses:
Dose levels:

1st group: 2000 mg/kg
2nd group: 2000 mg/kg

Reason for dose selection: As the LD50 value of HCFO-1223za, an analogous substance of the test article, exceeds 2000 mg/kg", the dose level for the 1st group was set at 2000 mg/kg. The dose level for the 2nd group was selected based on the mortality by day 3 after administration in the 1st group, according to the procedure shown in Annex 2.
No. of animals per sex per dose:
3
Control animals:
no
Statistics:
Statistical analysis was not conducted. Means and standard deviations were calculated for the body weight and body weight gain.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Staggering gait was noted 4 hrs after administration in 2 of 3 animals in the 1st group and 1 of 3 animals in the 2nd group, which disappeared by 6 hrs after administration. No abnormalities were noted in any animal from days 1 to 14 after administration.
Body weight:
Body weight increased normally in animals in both the 1st and 2nd groups.
Gross pathology:
No abnormalities were noted in any animal in the 1st or 2nd group.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
As described above, administration of HCFO-1233yd(Z) at 2000 mg/kg resulted in staggering gait in 3 of 6 animals 4 hrs after administration; however, these changes disappeared by 6 hrs after administration and no changes related to the test article administration were noted in body weight, body weight gain, or necropsy.

On the basis of these results, the LD50 value of HCFO-1233yd(Z) was estimated to be above 2000 mg/kg under the present study conditions. HCFO-1233yd(Z) was classified as Category 5 according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) toxicity categories.
Executive summary:

In an acute oral toxicity study, administration of HCFO-1233yd(Z) at 2000 mg/kg resulted in staggering gait in 3 of 6 animals 4 hrs after administration; however, these changes disappeared by 6 hrs after administration and no changes related to the test article administration were noted in body weight, body weight gain, or necropsy.

On the basis of these results, the LD50 value of HCFO-1233yd(Z) was estimated to be above 2000 mg/kg under the present study conditions. HCFO-1233yd(Z) was classified as Category 5 according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) toxicity categories.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

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
Study period:
14/03/2016 - 26/05/2016
Reliability:
1 (reliable without restriction)
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
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Toxicity - Oral

In an acute oral toxicity study, administration of HCFO-1233yd(Z) at 2000 mg/kg resulted in staggering gait in 3 of 6 animals 4 hrs after administration; however, these changes disappeared by 6 hrs after administration and no changes related to the test article administration were noted in body weight, body weight gain, or necropsy.

On the basis of these results, the LD50 value of HCFO-1233yd(Z) was estimated to be above 2000 mg/kg under the present study conditions.

Acute Toxicity - Inhalation

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 severe decrease in locomotor activity and coma on the remaining female.  On day 2, these symptoms disappeared.  No dead animals or abnormalities were observed following exposure to a concentration of 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 at the end of the observation period.

Justification for classification or non-classification

Decreased motor activity was noted in the acute toxicity studies, as well as the repeated-dose toxicity studies (discussed in the relevant section) at high doses and concentrations. These effects justify the classification of HCFO-1233yd(Z) for STOT SE 3 classification.

HCFO-1233yd(Z) is classified for STOT Single Exposure Category 3 according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Although the results of the acute inhalation study suggest that the LD50 for the substance may lie between 2590 and 21690 ppm based upon mortality observed at the highest concentration studied, further repeated-dose studies in rats showed that no mortality occurred over a 14-day period following exposure to 10,000 ppm. Therefore, the 4-hour LC50 in rats must lie above 10,000 ppm. Consequently, classification for acute inhalation toxicity is not justified.