Ethyl acetoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

The study was performed before GLP- and OECD-testing guidelines were available and in force.

A group of approximately 70 albino male and female rats, fasted for twenty-four hours were employed to establish an LD50 range for each product under test. Young adult rats which had not been used for previous test purposes were assigned to various dose levels at random. Both sexes were equally distributed. Body weight of the rats were 200-300 grams at the beginning of the study. Animals on the same dosage level were then placed in a common cage with free access to food and water. The animals were observed daily for a two week period.

No postmortem, or histopathology examinations were performed in this particular study.

GLP compliance:

no

Remarks:

GLP-guidelines not yet in force at date of the study

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

other: non-viscous clear liquid

Details on test material:

- Physical state: Colourless liquid

Specific details on test material used for the study:

no data

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Fasted albino rats were used in this study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The product under test was placed in a glass syringe and introduced through the esophagus into the stomach with a stainless steel catheter.

Doses:

7 dose groups (males & females) with dosages of:
- 0 mg/kg (control)
- 2000 mk/kg
- 4000 mg/kg
- 6400 mg/kg
- 8000 mg/kg
- 10000 mg/kg
- 12600 mg/kg
- 16000 mg/kg

No. of animals per sex per dose:

Five animals per sex and dose

Control animals:

yes

Details on study design:

no data

Statistics:

no data

Results and discussion

Preliminary study:

No preliminary test performed.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

12 300 mg/kg bw

Based on:

test mat.

95% CL:

10 300 - 14 800

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

10 800 mg/kg bw

Based on:

test mat.

95% CL:

9 300 - 12 500

Mortality:

No mortality was observed up to dose concentrations of 6400 mg/kg in males and up to 8000 mg/kg. Animals were found dead at 8000 mg/kg and above in males and at 10000 mg/kg and above in females. Details are given in the table below.

Clinical signs:

other: MALES: Males dosed at 2.0 g/kg and 4.0 g/kg exhibited moderate diarrhea for 2-3 days following intubation. Lethargy and moderate to severe diarrhea were noted at 6.4 g/kg and 8.0 g/kg. Rapid erratic respiration, lethargy, severe diarrhea, ruffled and unke

Gross pathology:

No postmortem, or histopathology examinations were performed in this particular study.

Other findings:

none

Any other information on results incl. tables

Mortality:

Dose Level (mg/kg)	No. of deaths (males)	Number of deaths (females)
2000	0	0
4000	0	0
6400	0	Not tested
8000	1 (day 2)	0
10000	1 (day 1)	2 (day 1 and 2)
12600	2 (day 1 and day 2)	4 (3 on day 1 and 1 on day 2)
16000	5 (day 1)	5 (day 1)

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity on Albino rats was determined to be 12300 mg/kg for males and 10800 mg/kg for females.

Executive summary:

A study was carried out equivalent or similar to EU Method B.1 and OECD Guideline 401 (Acute Oral Toxicity). 6 groups of 10 rats (5 male, 5 female) were treated by gavage with doses from 2000 up to 16000 mg/kg.Males and females dosed at 2.0 g/kg and 4.0 g/kg exhibited moderate diarrhea for 2-3 days following intubation. Lethargy and moderate to severe diarrhea were noted at 6.4 g/kg (only males tested) and 8.0 g/kg (both sexes). Rapid erratic respiration, lethargy, severe diarrhea, ruffled and unkempt coats were evident at the 10.0 g/kg and 12.6 g/kg dosage levels in both sexes. Death animals were observed at dose levels of 6400 mg/kg and above; for details refer to the above mentioned table. At 16000 mg/kg, the animals succumbed within 30 minutes after forced feeding. The LD50 was determined to be 12300 mg/kg for females and 10800 mg/kg for males.