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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, Guideline study (OECD)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl difluoroacetate
EC Number:
207-223-4
EC Name:
Ethyl difluoroacetate
Cas Number:
454-31-9
Molecular formula:
C4H6F2O2
IUPAC Name:
ethyl 2,2-difluoroacetate
Details on test material:
- Name of test material (as cited in study report): Ethyl difluoroacetate
- Analytical purity: 99.9%
- Lot/batch No.: 33244/106 A
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage condition of test material:
- Other: Density [g/mL]: 1.163
- The test substance was homogeneous by visual inspection.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Rat / Wistar / HanRcc:WIST(SPF)
- Source: RCC Ltd Laboratory Animal Services
- Age at study initiation: 8-12 years
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period: 16 hours before administration, but water was available ad libitum
- Housing: Single housing
- Diet (e.g. ad libitum): Kliba-Labordiät
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Acclimatization for at least 5 days before administration.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 – 24°C for
temperature.
- Humidity (%): 30 – 70% for relative humidity
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
Olive oil Ph.Eur./DAB
- Amount of vehicle (if gavage): Undiluted (2000 mg/kg) / Solution (300 mg/kg)
- Justification for choice of vehicle: Olive oil Ph.Eur./DAB had to be used to ensure homogeneity of the preparation.

DOSAGE PREPARATION (if unusual): The test-substance preparation of the 300 mg/kg administration group was produced shortly before the administration by stirring with a magnetic stirrer.
Doses:
300 mg/kg (3 animals)
2000 mg/kg - 2 different groups (6 animals)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals; these records are maintained with the raw data.
- other: mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
pathology: Necropsy with gross-pathology examination on the last day of the observation period after killing by CO2-inhalation in a
chamber with increasing concentrations over time.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no other abnormalities occured.
Mortality:
No mortality occurred.
Clinical signs:
Clinical observation in the 2000 mg/kg administration groups revealed impaired general state, dyspnoea, piloerection, exsiccosis, respiration sounds, reduced or no feces and were observed from hour 2 through to study day 2 after administration.
No clinical signs and findings were observed in the 300 mg/kg administration group.
Body weight:
The mean body weights of the administration groups increased throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (2000 mg/kg, 6 females and 300 mg/kg, 3 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the median lethal dose of Ethyl difluoroacetate after oral administration was found to be greater than 2000 mg/kg body weight in rats. Therefore, the test substance ethyl difluoroacetate is considered to be practically nontoxic after a single oral administration in rats.