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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Remarks:
Data are included only to justify the read-across approach of the dossier
Adequacy of study:
supporting 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:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Guanidine Nitrate
- Physical state: solid
- Analytical purity: 99,3 %
- Lot/batch No.: 010488
- Stability under test conditions: stated to be very stable when stored in dry conditions
- Storage condition of test material: in a container at ambient temperature and humidity in the dark

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female
Details on test animals 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:
other: unchanged (no vehicle)
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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.853 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 17.273 mg/L air (nominal)
Exp. duration:
4 h
Mortality:
There were no deaths.
Clinical signs:
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:
not classified
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.