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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-10-23, 1980-11-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
10 h light instead of 12. 2 doses only.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Solid
- Storage condition of test material: Stable at room temperature
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bred and raised on the premises
- Age at study initiation:
- Weight at study initiation: 197 - 252 g
- Fasting period before study:
- Housing: 10 animals per cage in Macrolon cages, Type 4 (Ehret, 783 Emmendingen/Germany)
- Diet (e.g. ad libitum): Ad libitum (NAFAG, Gossau/SG, Switzerland)
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 14/10

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglass exposure chamber
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: The rats were placed in separate PVC-tubes such that the snout and nostrils of the animals only
were exposed to the aerosol
- Source and rate of air: Air stream discharged into the exposure chamber at a rate of 10 L/min
- Method of conditioning air: Injection into an air stream
- System of generating particulates/aerosols: By introducing the solid test material with the aid of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream
- Method of particle size determination: 4 stage Cascade Impactor (C.F. Casella and Co., Ltd., Regent House, Britannia Walk, London) with Selectron filters (Schleicher and Schull AG, Feldbach, Switzerland) of 25 mm diameter and a pore size of 0.2 μm at an air flow rate of 17.5 L/min
-Pressure in air chamber: negative
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrically by sampling the test atmosphere through a Selectron filter of 50 mm diameter and a 0.2 μm pore size
Duration of exposure:
4 h
Concentrations:
762 ± 41 and 1951 ± 68 mg/m3 (measured)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 2 and 4 h as well as at 2 hours post-exposure and daily. Body weights were recorded immediately prior
to exposure and at day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross examination

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 951 mg/m³ air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 1 951 mg/m³ air (analytical)
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: AlI animals exposed to the test material recovered within 6 days. Slight dyspnoea and ruffled fur were noted in both treatment groups
Body weight:
not affected
Gross pathology:
No gross pathological changes were observed.
Other findings:
The particle size distribution analysis of the chamber airborne particles showed that at least 82 % were smaller than 7 µm in diameter for all exposures.

Any other information on results incl. tables

TABLE 2. PHARMACOTOXIC SIGNS

Exposure level (mg/m3) Pharmacotoxic sign Observation period
Hours Day
Exposure
1 2 4 24 2 3 4 5 6 7 8 9 10 11 12 13 14
762 ± 41 Exophthalmus

+
+ +










Ruffled fur

+
+ + +









1951 ± 68 Exophthalmus

+
+ + +









Ruffled fur

+
+ + + +








Mild = +; Moderate = ++; Severe = +++

TABLE 3. MEAN BODY WEIGHT  ± SD (GRAMS)

Day Sex Concentration (mg/m3)
0 (control) 762 ± 41 1951 ± 68
1 Male 241 ± 9 252 ± 8 202 ± 12
Female 223 ± 6 224 ± 7 197 ± 9
7 Male 291 ± 8 286 ± 13 258 ± 13
Female 232 ± 9 231 ± 7 211 ± 9
14 Male 332 ± 13 330 ± 17 300 ± 15
Female 254 ± 10 250 ± 6 227 ± 10

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met