Guanidinium nitrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end of 1988 - early 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Guanidinium nitrate

EC Number:

208-060-1

EC Name:

Guanidinium nitrate

Cas Number:

506-93-4

Molecular formula:

CH6N4O3

IUPAC Name:

amino(imino)methanaminium nitrate

impurity 1

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

impurity 2

Reference substance name:

Ammonium nitrate

EC Number:

229-347-8

EC Name:

Ammonium nitrate

Cas Number:

6484-52-2

Molecular formula:

H3N.HNO3

IUPAC Name:

Ammonium nitrate

impurity 3

Reference substance name:

4,6-diamino-1,3,5-triazin-2(1H)-one

EC Number:

211-455-1

EC Name:

4,6-diamino-1,3,5-triazin-2(1H)-one

Cas Number:

645-92-1

Molecular formula:

C3H5N5O

IUPAC Name:

4,6-diamino-1,3,5-triazin-2(1H)-one

impurity 4

Reference substance name:

(4,6-Diamino-1,3,5-triazine-2-yl)guanidine

Cas Number:

4405-08-7

Molecular formula:

C4H8N8

IUPAC Name:

(4,6-Diamino-1,3,5-triazine-2-yl)guanidine

impurity 5

Reference substance name:

Melamine

EC Number:

203-615-4

EC Name:

Melamine

Cas Number:

108-78-1

Molecular formula:

C3H6N6

IUPAC Name:

1,3,5-triazine-2,4,6-triamine

impurity 6

Reference substance name:

Cyanoguanidine

EC Number:

207-312-8

EC Name:

Cyanoguanidine

Cas Number:

461-58-5

Molecular formula:

C2H4N4

IUPAC Name:

1-cyanoguanidine

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 180 to 200 g
- Fasting period before study: not mentioned
- Housing: single room, groups of 5 by sex, grid-floor stainless steel cages
- Diet (e.g. ad libitum): not mentioned
- Water (e.g. ad libitum):not mentioned
- Acclimation period: at least 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C, at several occasions 18 to 29 °C
- Humidity (%): 40 to 70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

head only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical aluminium exposure chamber
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: restrained in plastic tubes, nares only project into the chamber
- Source and rate of air: clean dry filtered air, diluent air flow 10.0 to 10.3 L/min
- Method of conditioning air: compression
- System of generating particulates/aerosols: Wright dust feed generator
- Method of particle size determination: Delcron CS5 Cascade Impactor with 5 separation stages (0.5, 1.0, 2.0, 4.0, 8.0 μm)
- Temperature, humidity in air chamber: 18 to 20 °C, 37 to 55 % humidity

TEST ATMOSPHERE
- Brief description of analytical method used: For the determination of the nominal concentration, the total weight of test article used and the volume Q of diluent air used to generate the test atmosphere were recorded and the nominal concentration of the test article in the exposure chamber was calculated as follows:
Nominal concentration (mg/L) = weight of test article used (mg) / flowrate (L/min) x duration (min)
- Samples taken from breathing zone: not specified

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: particle size analysis was performed
- MMAD (Mass median aerodynamic diameter): 5.52 μm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The study was performed as a limit test.
mean measured concentration: 0.853 mg/L
nominal concentration: 17.273 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: hourly during exposure and for the remainder of the exposure day then daily for 14 days
- Frtequency of weighing: day of dosing, days 8 and 15 of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, lung weight

Statistics:

means and standard deviations calculated where appropriate

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.853 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 17.273 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths.

Clinical signs:

other: Slight clinical signs of staining and wetting of the fur in the test group disappeared by day 4.

Body weight:

There was no treatment-related effect on body weight.

Gross pathology:

There were no treatment-related changes in lung weight or in macroscopic appearance at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LC 50 of Guanidine Nitrate was determined to be > 0.853 mg/L air (analytical) in this study. This concentration was the maximum possible under conditions of this study, generated from a nominal concentration of 17.273 mg/L. No animal died and no treatment related clinical signs were observed.

Executive summary:

In an acute inhalation toxicity study performed similar to OECD Guideline 403 5 male and 5 female young adult Crl:CD(SD)BR rats were exposed by inhalation route to micronized Guanidine Nitrate (99.3 % a.i.) for 4 hours to head only at a chamber concentration of 0.853 mg/L. The corresponding nominal concentration was 17.273 mg/L and the mass median aerodynamic diameter of the particles in the atmosphere was 5.52 µm. The nominal concentration was the maximum practical for the generator used and the resulting analytical concentration the maximum possible under conditions of this study. Animals then were observed for 14 days.

LC₅₀      Combined =  > 0.853 mg/L air (analytical)

             Combined =  > 17.273 mg/L air (nominal)

No animals died and there were no treatment related clinical signs, necropsy findings( including lung weights) or changes in body weight, exceptof staining and wetting of the fur, which disappeared by day 4.