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Description of key information

One key study is available for the end point acute oral toxicity. The study was performed according to OECD guideline 423 and under the conditions of GLP.

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:
October 2017 - December 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 449935-248
- Expiration date of the lot/batch: 30 March 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refridgerator (2-8ºC)
- Stability under test conditions: stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Allowed to warm to room temperature for at least 30 minutes before dosing
Species:
rat
Strain:
Wistar
Remarks:
(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9 weeks old
- Weight at study initiation: 151 to 175 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) piror to dosing and until 3-4 hours after administration of the test item. Water was available
- Housing: (up to 5 animals of the same sex and dosing group together) Polycarbonate cages (Makrolon, MIV typ; height 18cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J Rettenmaier & Sohne GmbH = CO. K.G, Rosenberg, Germany)
- Diet (e.g. ad libitum): Pelleted rodent diet ( SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany) provided ad libitum, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles
- Acclimation period: 5 days before the commencement of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24ºC (daily mean 21ºC)
- Humidity (%): 40-70% (actual daily mean 46 - 58%)
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows:
Dose level (g/kg) / spec.gravity or density (g/mL)


DOSAGE PREPARATION (if unusual):
The dosing formulations were stirred continuously during dose administration. With the exception of the test item administered to the first dose group which was not stirred during dose administration.
Evaluation: As the test item was a clear liquid stirring would not have affected the test item dosed. Therefore this deviation has no impact on the study integrity


Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 (in two groups of 3)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Post-dose observations were made at periodic intervals on the day of dosing and once daily thereafter. Body weights were recorded on day 1, 8 and 15. A fasted weight recorded on the day of dosing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
other: Lethargy, flat posture, hunched posture, uncoordinated movements, slow breathing, shallow respiration, quick breathing, piloerection and/or ptosis were noted for the animals on Days 1 and/or 2.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Analysis

All results presented in the tables of the report (as attached to this study record) are calculated using values as per the raw data rounding procedure and may not be exactly reproduced from the individual data presented.

The oral LD50 value of the test item was ranked within the following ranges: 0-5, 5-50, 50-300 or 300-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w. The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

The results were evaluated according to:

·        Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments).

·        Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate in Wistar rats was established to exceed 2000 mg/kg body weight..
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Executive summary:

The objective of this study was todetermine the potential toxicity of 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate, when given by oral gavage at a single dose to rats of a single sex at one or more defined doses to evaluate the potential reversibility of any findings.

 

The study was carried out in compliance with the guidelines described in:

·        OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

·        EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method"

·        EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

·        JMAFF Guidelines (2000), including the most recent revisions.

 

2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

 

No mortality occurred.

Lethargy, flat posture, hunched posture, uncoordinated movements, slow breathing, shallow respiration, quick breathing, piloerection and/or ptosis were noted for the animals on Days 1 and/or 2.

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

No abnormalities were found at macroscopic post mortem examination of the animals.

 

The oral LD50 value of 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate in Wistar rats was established to exceed 2000 mg/kg body weight..

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The key study is considered to be a Klimisch reliability 1.

Additional information

Justification for classification or non-classification

The oral LD50 value of 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results, 2,2,2-trifluoro-1-(trifluoromethyl)ethyl methacrylate does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).