Dimethyl 3-oxoglutarate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Before GLP implementation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl 3-oxoglutarate

EC Number:

217-385-8

EC Name:

Dimethyl 3-oxoglutarate

Cas Number:

1830-54-2

Molecular formula:

C7H10O5

IUPAC Name:

dimethyl 3-oxoglutarate

Details on test material:

- Name of test material (as cited in study report): P5110
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance):
- Substance type: organic
- Physical state: clear liquid
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: stable
- Storage condition of test material: at room temperature
- Other:

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Batin and Kingman Ltd., Grimston, Aldbrough, Nr. Hull
- Age at study initiation:
- Weight at study initiation: 142 -167 g
- Fasting period before study: overnight (18-20 hrs)
- Housing: Groups of 2 (dose-range finding study); Groups of 5 (main study) by sex and dose group in solid bottomed plastic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -25
- Humidity (%): 40-60
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
Dose range finding test: 5, 25, 125, 500 mg/ml
Main study: 200, 283, 400, 566 mg/ml

- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 5660 mg/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

Dose range-finding study
50 mg/kg
250 mg/kg
1250 mg/kg
5000 mg/kg


Main study
2000 mg/kg
2830 mg/kg
4000 mg/kg
5660 mg/kg

No. of animals per sex per dose:

Dose range-finding study
50 mg/kg 2 male/2 female
250 mg/kg 2 male/2 female
1250 mg/kg 2 male/2 female
5000 mg/kg 2 male/2 female

Main study
2000 mg/kg 5 male/5 female
2830 mg/kg 5 male/5 female
4000 mg/kg 5 male/5 female
5660 mg/kg 5 male/5 female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 15 min, 1, 2 and 4 hours after the treatment and once daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Probit analisys (Finney D.J. (1964), Statistical Method for Biological Assay, 2nd Edition, London Charles Griffin).

Results and discussion

Preliminary study:

Dose-range finding study
The mortalities indicated an LD50 in the range 1250- 5000 mg/kg.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 770 mg/kg bw

Based on:

test mat.

95% CL:

> 4 216 - < 5 397

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

4 476 mg/kg bw

Based on:

test mat.

95% CL:

> 3 688 - < 5 431

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

5 499 mg/kg bw

Based on:

test mat.

95% CL:

> 4 430 - 6 826

Mortality:

Eight animals (4 male, 4 female) treated with 5660 mg/kg and 2 males treated with 4000 mg/kg died during the study. All deaths were recorded between 15 minutes and 24 hours of dosing. No deaths were recorded in animals treated with 2000 and 2830 mg/kg.

Clinical signs:

All sings of toxicity noted in animals treated with 5660 mg/kg occurred during the day of dosing.
Sings commonly recorded in this group were lethargy or prostration, piloerection, hunched posture and slow shallow or laboured respiration.
The 2 surviving animals appeared normal 24 hours after treatment and througout the remainder of the observation period.

Lethargy was also noted in 4 animals treated with 4000 mg/kg between 15 minutes and 1 hour after treatment. Other sings of toxicity recorded during the day of dosing were piloerection and laboured respiration. All surviving animals appeared normal 2 hours after treatment and throughout the observation period.

One female treated with 2830 mg/kg appeared lethargic with piloerection 1 hour after dosing. This animal recovered and no further signs of toxicity were noted during the observation period.

All animals treated with 2000 mg/kg appered normal throughout the observation period.

Body weight:

All surviving animals showed normal body weight gain throughout the observation period.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the results acute oral toxic classification is not needed.