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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1986

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Dust in air concentration determination is not reliable. Exact animal exposure can not be determined.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Principles of method if other than guideline:

Deviation from guideline: granulometry was not determined from the sample powder. Dust concentration in air was not measured by an approriate analitical method.

GLP compliance:

no

Test type:

other: acute inhalation toxicity sudy

Limit test:

yes

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):
- Substance type: organic
- Physical state: white or beige 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: soluble in ethyleneglycol, propyleneglycol, DMSO

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:
- Fasting period before study: 12h
- Housing: 5-5 animals/cages
- Diet (e.g. ad libitum): LATI
- Water (e.g. ad libitum): ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 40-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12h/12 h

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
- Exposure chamber volume: 0.3 m3
- Method of holding animals in test chamber: connecting to glass tubes in a 40 cm wall
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination:
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: calculation
- Samples taken from breathing zone: yes/no

VEHICLE
- Composition of vehicle (if applicable): DMSO
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not determined
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not determined

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

Analytical verification of test atmosphere concentrations:

no

Remarks:

only calculation

Duration of exposure:

4 h

Concentrations:

ALC

Concentration Gender Dead
1390 mg/m3; Male/Female --
2660 mg/m3; Male/Female --
3320 mg/m3; Male/Female --


LC50
2600 mg/m3; Male 1/8 72 hours
Female 0/8 --

2870 mg/m3; Male 2/8 72 hours
Female 0/8 --

3190 mg/m3 Male 2/8 48/72 hours
Female 0/8 --

No. of animals per sex per dose:

8 males/8 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0; 1; 2; 3; 4; 7; 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, relative organ weights, histopathology

Results and discussion

Mortality:

Yes, only males.

Clinical signs:

other: No.

Body weight:

Body weight gain of treated animals was smaller, than the untreated animals, especially for females.

Gross pathology:

Mortality case: Diffuse lung oedema, and liver effect (size increase).

Survivor case: Small oedema in lungs, and liver effect.
Significant lung and liver organ weight increase.

Any other information on results incl. tables

Body weight change after treatment in gramm (g)

Males (average value, n = 8)

Concentration (mg/m3)	0	1 day	2 day	3 day	7 day	14 day	Body weight increase (g)
2600	230.10 +/-16.90	231.35 +/-29.97	235.25 +/- 9.91	241.71 +/- 40.35	253.33 +/- 43.66	238.36 +/- 24.57	+38 .26
2870	248.75 +/-31.36	252.50 +/-29.15	251.25 +/- 26.42	263.75 +/-24.45	268.57 +/- 32.87	288.00 +/- 27.74	+39.25
3190	261.25 +/-19.59	271.25 +/-18.07	272.50 +/-19.08	283.75 +/-19.95	287.50+/-20.52	301.28 +/- 21.49	+40.03
Control	220.15+/- 21.62	224.15 +/- 20.14	235.40 +/-22.17	241.17 +/- 19.51	259.80 +/- 22.14	269.34 +/- 21.17	+49.19
Control (untreated)	219.24 +/- 17.48	225.37 +/- 18.23	232.20+/- 25.10	240.27 +/- 23.39	256.14 +/- 21.16	269.15 +/- 22.42	+49.91

Females (average value, n = 8)

Concentration (mg/m3)	0	1 day	2 day	3 day	7 day	14 day	Body weight increase (g)
2600	203.75 +/-7.44	227.50 +/-20.52	237.50 +/- 27.64	231.25 +/- 9.91	220.17 +/- 32.95	240.50 +/- 36.93	+36.75
2870	203.75 +/-9.16	223.75 +/-17.67	225.62 +/- 19.89	223.75 +/-16.85	217.14 +/- 17.99	235.00 +/- 11.35	+31.25
3190	223.75 +/-18.46	218.75 +/-17.26	221.62 +/-20.31	228.75 +/- 20.31	230.17 +/- 17.72	252.50 +/- 18.32	+23.75
Control	212.44 +/- 11.73	220.31 +/-13.47	225.49 +/-10.22	226.31 +/-12.94	230.62 +/- 15.12	254.78 +/- 15.64	+42.34
Control (untreated)	195.10+/- 14.60	197.33 +/- 12.41	204.21 +/-14.97	211.43 +/- 15.90	220.00 +/- 13.47	239.80 +/- 17.17	+44.70

 

Relative organ weight (100 g body weight) of male rats (average, n= 10)

Concentration (mg/m3)	Brain	Heart	Lung	Liver	Spleen	Kidney	Adrenal	Thymus
2600	0.60 +/-0.07	0.32 +/- 0.05	0.76 +/- 0.09	5.54 +/- 0.91	0.26 +/- 0.10	0.80 +/- 0.14	0.01 +/- 0.001	0.013 +/- 0.02
2870	0.55 +/- 0.06	0.32 +/- 0.05	0.84 +/- 0.15	5.05 +/- 0.85	0.25 +/- 0.03	0.82 +/- 0.12	0.01 +/- 0.005	0.016 +/- 0.03
3190	0.58 +/-0.04	0.28 +/- 0.36	0.84 +/- 0.13	4.28 +/-0.94	0.45 +/- 0.32	0.72 +/- 0.11	0.01 +/- 0.006	0.13 +/- 0.02
Control	0.58 +/-0.04	0.28 +/- 0.04	0.84 +/-0.13	4.28 +/-0.94	0.45 +/-0.32	0.73 +/-0.11	0.01 +/-0.006	0.13 +/-0.02
Control (untreated)	0.58 +/-0.04	0.33 +/- 0.03	0.65 +/-0.09	3.86 +/-0.18	0.21 +/-0.22	0.72 +/-0.09	0.01 +/-0.001	0.14 +/-0.04

Relative organ weight (100 g body weight) of female rats (average, n= 10)

Concentration (mg/m3)	Brain	Heart	Lung	Liver	Spleen	Kidney	Adrenal	Thymus
2600	0.54 +/-0.08	0.33 +/- 0.09	0.89 +/- 0.18	4.87 +/- 0.72	0.22 +/- 0.03	0.77 +/- 0.11	0.02 +/- 0.01	0.17 +/- 0.02
2870	0.58 +/- 0.04	0.29 +/- 0.03	0.87+/- 0.14	4.65 +/- 0.55	0.22 +/- 0.03	0.70 +/- 0.15	0.01 +/- 0.002	0.16 +/- 0.05
3190	0.54 +/-0.05	0.32 +/- 0.02	0.81 +/- 0.19	4.58 +/-0.46	0.24 +/- 0.03	0.78 +/- 0.02	0.02+/- 0.002	0.18 +/- 0.04
Control	0.56 +/-0.03	0.31+/- 0.02	0.81 +/-0.19	4.58 +/-0.46	0.24 +/-0.03	0.78 +/-0.02	0.02 +/-0.002	0.18 +/-0.04
Control (untreated)	0.55 +/-0.03	0.32 +/- 0.03	0.49 +/-0.05	3.74 +/-0.17	0.21 +/-0.02	0.74 +/-0.02	0.01 +/-0.001	0.14 +/-0.02

Applicant's summary and conclusion

Interpretation of results:

other: toxic effects above 3000 mg/m3

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The inhalation acute toxicity was not determined, because of analitycal problems of the test materials.
According to the observation of the animal studies toxic effect was observed above 3000 mg/m3.