Ethyl 4,4,4-trifluoroacetoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November - December 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, non-GLP

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 4,4,4-trifluoroacetoacetate

EC Number:

206-750-7

EC Name:

Ethyl 4,4,4-trifluoroacetoacetate

Cas Number:

372-31-6

Molecular formula:

C6H7F3O3

IUPAC Name:

ethyl 4,4,4-trifluoro-3-oxobutanoate

Test material form:

other: clear liquid

Details on test material:

- Name of test material (as cited in study report): P5117
- Physical state: clear, colourless liquid
- Purity test date: 21-Oct-1980
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: stored at ambient temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin & Kingman Ltd., Grimston, Aldbrough, Nr. Hull
- Age at study initiation: not given
- Weight at study initiation: 125-155 g
- Housing: gang housing; 5 animals per cage in main study
- Diet (e.g. ad libitum): Rat and Mouse No. 1 Modified, BP Nutrition (UK) Ltd., Stepfield, Witham, Essex
- Water (e.g. ad libitum): Tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-25°C
- Humidity (%): ambient humidity
- Photoperiod (hrs dark / hrs light): 12 hours artificial light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test article preparations were administered once only by oral gavage using a metal stomach tube (14 gauge x 8 cm, Stand Medicals Ltd., Manchester) attached to a 2 ml disposable plastic syringe.

Doses:

PRETEST:
- 50, 250, 1250 and 5000 mg/kg

MAIN STUDY:
- 400, 566, 800 and 1131 mg/kg

No. of animals per sex per dose:

PRETEST:
- 2 males & 2 females

MAIN STUDY:
- 5 males & 5 females

Control animals:

yes

Details on study design:

APPEARANCE, BEHAVIOUR AND GENERAL OBSERVATIONS:
All animals were observed for overt signs of toxicity or behavioural change at 0.25, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days. All gross or visible toxic or pharmacological effects were recorded.

BODY WEIGHTS:
Individual body weights were recorded on the day before treatment (Day 1), on the day of treatment and at 7 and 14 days after treatment.

NECROPSY:
Animals dying during the working day were subjected to a gross necropsy examination. Animals surviving at the end of the study were killed by exposure to high levels of carbon dioxide.

Statistics:

The acute oral median lethal dose (LD50) and 95% fiducial limits for combined male and female groups, were calculated using a pro bit analysis (Finney D.J. (1964), Statistical Method for Biological Assay, 2nd Edition, London, Charles Griffin).

Results and discussion

Preliminary study:

The mortalities obsreved in the pretest indicated an LDSO of approximately 1250 mg/kg.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

855 mg/kg bw

Based on:

test mat.

95% CL:

741 - 986

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

765 mg/kg bw

Based on:

test mat.

95% CL:

630 - 929

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

954 mg/kg bw

Based on:

test mat.

95% CL:

801 - 1 135

Mortality:

One female treated with 566 mg/kg, 3 animals (1 male, 2 females) treated with 800 mg/kg and 9 animals (4 males, 5 females) treated with 1131 mg/kg died during the observation period. All deaths occurred within 15 minutes and 24 hours after treatment.

Clinical signs:

other: 400 mg/kg: Lethargy and hunched posture were evident throughout the day of dosing. All animals appeared normal 24 hours after treatment. 566 mg/kg: All surviving, animals appeared lethargic throughout the day of dosing and this was maintained in 2 animal

Gross pathology:

Any animals found dead during the working day were subjected to a gross necropsy examination. Congested lungs and distended stomachs were described in the majority of these animals. One group 8 animal, male 13, treated with 1131 mg/kg showed a mottled appearance of the gastrointestinal tract. No other abnormalities were described.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of P5117 on Wistar rats was found to be:
- combined males and females: 855 mg/kg
- males: 954 mg/kg
- females: 765 mg/kg

Executive summary:

A study was carried out according to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity) on Albino Wistar rats. 4 groups of 4 rats (2 male, 2 female) for Dose-Range-Finding and 4 groups of 10 rats (5 male, 5 female) for the main study were treated by gavage with doses from 50 up to 5000 mg/kg in the pretest and 400 up to 1131 mg/kg in the main study. Mortality and a number of clinical signs were observed at mid and high dose group animals of the main study. Animals showed normal body weight gains at the end of the 14 d observation period. At necropsy, there were some tratment related findings noted in the highest dose group only.

The acute oral LD50 of P5117 on Wistar rats was found to be:

- combined males and females: 855 mg/kg

- males: 954 mg/kg

- females: 765 mg/kg