Ethyl 3-amino-1H-pyrazole-4-carboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

Similar to OECD 423.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 3-amino-1H-pyrazole-4-carboxylate

EC Number:

230-262-3

EC Name:

Ethyl 3-amino-1H-pyrazole-4-carboxylate

Cas Number:

6994-25-8

Molecular formula:

C6H9N3O2

IUPAC Name:

ethyl 3-amino-1H-pyrazole-4-carboxylate

Details on test material:

- Name of test material (as cited in study report): Karbetoxi-pirazol
- 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): see Fig.
- Substance type: organic
- Physical state: white or yellowish-white crystalline powder
- 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: 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:
- Age at study initiation:
- Weight at study initiation: 193.00 +/-15.3 g (male), 153.00 +/- 6.3 g (female)
- Fasting period before study: 18 h
- Housing:
- Diet (e.g. ad libitum): LATI food
- Water (e.g. ad libitum): ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1.5
- Humidity (%):
- 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:

other: 1 % methylcellulose in water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1 % methylcellulose
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Dose selection according to Deichmann-Le Blanck.
5 doses, 3-3 animals/dose.

Doses:

360 mg/kg
510 mg/kg
552 mg/kg
600 mg/kg
620 mg/kg
710 mg/kg
840 mg/kg
1000 mg/kg

No. of animals per sex per dose:

Dose selection (approximate LD50 test)
360 mg/kg 2 male/2 female
510 mg/kg 2 male/2 female
710 mg/kg 2 male/2 female
1400 mg/kg 2 male/2 female
2600 mg/kg 2 male/2 female




360 mg/kg 6 male/6 female
510 mg/kg 6 male/6 female
552 mg/kg 6 male/6 female
600 mg/kg 6 male/6 female
620 mg/kg 6 male/6 female
710 mg/kg 6 male/6 female
840 mg/kg 6 male/6 female
1000 mg/kg 6 male/6 female

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 2 h, 4h, 24h, 48 h, 72 h and 7. day, 14. day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, relative organ weights, histopathology

Results and discussion

Preliminary study:

Dose Male Female
(mg/kg) (dead/alive) (dead/alive)
360 ( -/2) symptom free survivors (-/2) survivors with symptoms
510 (- /2) survivors with symptoms (2/2) dead in 4 hours
710 (- /2) survivors with symptoms (2/2) dead in 4 hours
1400 (2/2) dead in 2 hours (2/2) dead in 1/2 hours
2600 (2/2) dead in 1/2 hours (2/2) dead in 10 min.

Females were more sensitive, they exited at 510 mg/kg doses.
Males were exited at 2600 mg/kg doses.

Approximative lethal dose is 2600 mg/kg.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

2 600 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

673.674 mg/kg bw

Based on:

test mat.

95% CL:

> 611.44 - < 747.17

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

573.27 mg/kg bw

Based on:

test mat.

95% CL:

> 529.27 - < 620.14

Mortality:

Males

Doses Dead/Alive Time
360 mg/kg 0/6 --
510 mg/kg 1/6 in 4 hours
552 mg/kg 1/6 in 4 hours
600 mg/kg 1/6 between 4-48 hours
620 mg/kg 3/6 in 4 hours
710 mg/kg 3/6 2-72 hours
840 mg/kg 5/6 in 4 hours
1000 mg/kg 6/6 in 1/2 hours

Clinical signs:

other: Disorientation. Cramps, rolling after 10-15 minutes time. Cyanosis, tachicardia, death. Survivors hair were ruffled. No food consumptions because lack of appetite in the first 2 days. After the 3rd-4th day the body weight gain became normal.

Gross pathology:

Clinical signs and pathology has shown nerve system effects.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance is harmful if swallowed according to EU classifications.