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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 November 2009 to 11 December 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted in compliance with GLP and to EU and OECD guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2,3,3-tetrafluorooxetane
EC Number:
700-202-5
Cas Number:
765-63-9
Molecular formula:
C3H2F4O
IUPAC Name:
2,2,3,3-tetrafluorooxetane
Details on test material:
- Name of test material (as cited in study report): 2,2,3,3-tetrafluorooxetane (TFO)
- Substance type: Not stated
- Physical state: Liquid
- Analytical purity: 99%
- Purity test date: Not stated
- Lot/batch No.: TFOS285001
- Expiration date of the lot/batch: 30 April 2010
- Stability under test conditions: Not stated
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
CD-1
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 218 to 284 g
- Fasting period before study: Yes
- Housing: Animals were housed inside a barriered rodent facility. The facility was designed and operated to minimise the entry of external biological and chemical agents and to minimise the transference of such agents between rooms.
- Diet (e.g. ad libitum): Rat and Mouse No. 1 Maintenance Diet
- Water (e.g. ad libitum): Potable water taken from the public supply available ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 20 November 2009 To: 11 December 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Not given
- Lot/batch no. (if required): Not required
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels for the study were chosen in compliance with the study guidelines. As no previous toxicological information was available the initial dose level was 300 mg/kg.
Doses:
300, 2000 mg/kg
No. of animals per sex per dose:
3 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations once every morning and end of the day.
Weighing: Days 1, 8 and 15 or death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: macroscopic pathology

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Mortality:
One female dosed at 300 mg/kg died on Day 5. One female dosed at 300 mg/kg died on Day 1. All three females dosed at 2000 mg/kg died on Day 1.
Clinical signs:
Clinical signs observed prior to death in the rats that died included the following:
died day 5 (300 mg/kg): loose faeces, piloerection, yellow staining in UG area, underactive, hunched posture and partially closed eyelids.
died day1 (300 mg/kg): loose faeces, yellow staining in UG area, reduced body tone, reduced body temperature, irregular breathing, shallow breathing, flat posture and underactive.
Died day 1 (2000 mg/kg): flat posture, unsteady gait, fast respiration, underactive, irregular respiration and convulsions.

Clinical signs in other rats: Clinical signs of reaction to treatment comprised piloerection in all four surviving females at 300 mg/kg, loose faeces, hunched posture, brown staining on head and yellow urine staining, in three surviving females and reduced body tone, overactive, thin build, limited use of limbs and elevated gait, seen in individual surviving females dosed at 300 mg/kg. These signs were first noted from approximately 30 minutes after dosing and had resolved by Day 14.
Body weight:
All rats which died, body weight loss recorded at death.
Low bodyweight gains were noted for two females dosed at 300 mg/kg and a bodyweight loss was noted for one female dosed at 300 mg/kg on Day 8. All other surviving animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Rat died day 5 (300 mg/kg): Macroscopic findings comprised congestion of the subcutaneous tissue, duodenum, small and large intestine and caecum, pallor of the liver, spleen and stomach, enlarged, swollen or thickened stomach, small caecum and solid white contents in the stomach.
Rat died day 1 (300 mg/kg):Macroscopic findings comprised congested subcutaneous tissue, pallor of lungs and kidneys, yellow fluid contents in the stomach, duodenum, small and large intestines and small caecum.
Rats died day 1 (2000 mg/kg): Macroscopic findings comprised congestion of the lungs, liver, stomach, duodenum, small and large intestines and caecum, pallor of the lungs and kidneys, small stomach, gaseous distension of the stomach and yellow fluid contents in the duodenum, small and large intestines.
Surviving rats: Macroscopic examination at study termination on Day 15 revealed pallor of the liver in one female; pallor of the kidneys in two females; enlarged, swollen or thickened spleen in two females; enlarged, swollen or thickened stomach in four females, adhesions to the thoracic/abdominal wall in four females, gaseous distension in the caecum of two females and the stomach epithelium had sloughed off in two females treated at 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
TFO is included in Category 4, according to the Globally Harmonised System (GHS),
Executive summary:

An acute toxicity rat study on 2,2,3,3-tetrafluorooxetane (TFO) was carried out by Huntingdon Life Sciences, Huntingdon Research Centre, UK on behalf of the Shin-Etsu Chemical, Japan.

The acute toxic class method is a stepwise procedure that uses three animals of a single sex per step. Depending on the mortality and/or the moribund status of the animals, on average two to four steps may be necessary to allow a judgement on the acute toxicity of the test substance. The study was conducted in accordance with Good Laboratory Practice Standards.

Two groups of three fasted female rats received a single oral gavage dose of the test substance, formulated in corn oil, at a dose level of 300 mg/kg bodyweight. As results at this dose level indicated the acute (median) lethal oral dose of the test substance to be greater than 300 mg/kg bodyweight, in compliance with the study guidelines a further group of three fasted females were similarly dosed at 2000 mg/kg bodyweight to complete the study.

The acute median lethal oral dose (LD50) to rats of TFO was demonstrated to be between 300 and 2000 mg/kg bodyweight.

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