Ethyl 4,4,4-trifluoroacetoacetate

Endpoint summary

Description of key information

ACUTE ORAL TOXICITY:
A study was carried out according to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity) on Albino Wistar rats. 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

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:

November - December 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, non-GLP

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

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

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

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).

Preliminary study:

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

855 mg/kg bw

Based on:

test mat.

95% CL:

741 - 986

Sex:

female

Dose descriptor:

LD50

Effect level:

765 mg/kg bw

Based on:

test mat.

95% CL:

630 - 929

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.

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

765 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Klimisch 2 guideline study, non-GLP

Justification for classification or non-classification

Based on the data available the substance the substance needs to be classified or labeled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP) as follows:

Regulation 1272/2008/EC (CLP):

Warning

Acute toxicity; Category 4 ; Oral

H302: Harmful if swallowed

Directive 67/548/EEC (DSD):

Xn, harmful

R22: Harmful if swallowed.