Methyl acetoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

the study was performed before GLP- and OECD-testing guidelines were available and in force; therefore the study was considered to have Klimisch 2, however itprovides enough information to assess the acute toxicity after to rats after oral application

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

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

Reference substance name:

Methyl acetoacetate

EC Number:

203-299-8

EC Name:

Methyl acetoacetate

Cas Number:

105-45-3

Molecular formula:

C5H8O3

IUPAC Name:

methyl 3-oxobutanoate

Test material form:

other: non-viscous clear liquid

Details on test material:

- Physical state: Colourless liquid

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:

6 dose groups (males & females) with dosages of:
- 0 mg/kg (control)
- 1000 mg/kg
- 2000 mg/kg
- 2500 mg/kg
- 3200 mg/kg
- 4000 mg/kg
- 8000 mg/kg

No. of animals per sex per dose:

Five animals per sex and dose

Control animals:

yes

Details on study design:

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 was 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.

Statistics:

no data

Results and discussion

Preliminary study:

No preliminary test performed.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 580 mg/kg bw

Based on:

test mat.

95% CL:

2 230 - 2 980

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 370 mg/kg bw

Based on:

test mat.

95% CL:

2 920 - 3 900

Mortality:

No mortality was observed at dose concentrations of 1000 and 2000 mg/kg. Animals were found dead at 2500 mg/kg and above in males and at 3200 mg/kg and above in females. Details are given in the table below.

Clinical signs:

other: Males & females dosed at 1.0 g/kg and 2.0 g/kg were sluggish and unkempt following intubation. Normalcy prevailed within 48 hours. Lethargy, nasal hemorrhage and dirty unkempt coats were noted in all animals dosed at levels ranging from 2.5 g/kg. to 4.0 g

Gross pathology:

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

Other findings:

no data

Any other information on results incl. tables

Mortality:

Dose Level (mg/kg)	No. of deaths (males)	Number of deaths (females)
1000	0	0
2000	0	0
2500	3	0
3200	4	2
4000	5 (4 at day 1 & 1 at day 3)	4
8000	5	5

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 2580 mg/kg for males and 3370 mg/kg for females.

Executive summary:

The 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 1000 up to 8000 mg/kg.Males & females dosed at 1.0 g/kg and 2.0 g/kg were sluggish and unkempt following intubation. Normalcy prevailed within 48 hours. Lethargy, nasal hemorrhage and dirty unkempt coats were noted in all animals dosed at levels ranging from 2.5 g/kg. to 4.0 g/kg. Death animals were observed at dose levels of 2500 mg/kg and above. At 8000 mg/kg, the animals were comatose immediately after forced feeding and succumbed within 15 minutes.The LD50 value obtained for males was 2580 mg/kg bw and for females 3370 mg/kg bw.