Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
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)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: EN 63699.02

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Raised on the premises
- Weight prior to exposure: average for males: 207-235 g; average for females: 188-212 g
- Housing: The males and females were segregated and kept in Macrolon cages, type 4 (10 animals to a cage)
- Diet: ad libitum rat food - NAFAG, Gossau SG, Switzerland
- Water: ad libitum water
- Acclimation period: a minimum of 4 days

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

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
TESTING PROCEDURE:
For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snouts and nostrils of the animals only were exposed to the aerosol.

During the exposure period at approximately the same times as chamber concentration was measured, the following parameters were determined inside the inhalation cylinder: temperature (with a THERM 2104 contact thermometer, Ahlborn Mess- und Regeltechnik, 815 Holzkirchen, Germany), relative humidity (with a VÆSALA Humidity Indicator HMI 11, Kelag AG, 8057 Zurich, Switzerland) and oxygen content (with a DRAEGER E 15 stationary control system, Draegerwerk AG, Lübeck, Germany).

After a 4 hour inhalation exposure the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days.

GENERATION OF TEST ATMOSPHERE
The aerosol was generated by injecting two different concentrations of the solid test material with the help of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream which was discharged into the exposure chamber at a rate of 10 L/min.

The control animals were exposed to filtered air under the same conditions as described above.

The concentration and the paricle size distribution of the aerosol in the breathing zone vicinity of the animals were monitored at regular intervals throughout the aerosol exposure. The concentration was determined 5 times gravimetrically by sampling the test atmosphere though a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured twice with a 4 stage Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2119±168 and 1365±47 mg/m³
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded immediately prior to exposure (control weights) and at day 7 and 14; physical condition and incidence of death were monitored throughout an observation period of 14 days
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 119 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred in the control group or the 1365 and 2119 mg/m³ exposure groups.
Clinical signs:
The surviving animals recovered within 7 to 8 days after the exposure period. Slight dyspnoea, exophthalmus,ruffled fur,and curved body position were noted during and after exposure to 1365 and 2119 mg/m³ of the test material.
Body weight:
Overall body weights and weight gains were within normal limits when measured at day 7 and 14 of the observation period.
Gross pathology:
No gross pathology was noted in the control or either treatment groups at necropsy.
Other findings:
Particle size distribution analysis of the chamber airborne particles showed that 80% were smaller than 7 µm in diameter.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met