Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Mar. 11, 1980 to Apr. 10, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

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:
4-day acclimatization period, 10-hour light cycle, and dose selected, no autopsy data for single animals
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: TiF:RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy premises
- Age at study initiation: young adults
- Weight at study initiation: 204-211 g for males and 184-193 g for females
- Housing: 10 animals per cage, males and females segregated and kept in Macrolon cages, type 4
- Diet (e.g. ad libitum): NAFAG, Gosaau AG, Switzerland ad libitum
- Water (e.g. ad libitum): asd libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°C
- Humidity (%): 55+/-10%
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 10 h light/14 h dark

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: ethanol 94% + 1% cyclohexane
Details on inhalation exposure:
Inhalation:
Rats were kept in separate PVC tubes positioned so that only snout and nostrils were exposed. Temperature, relative humidity, and oxygen content were monitored thoughout the 4-hour exposure period.

Preparation of aerosol:
A 30% suspension of TK 12599 in ethanol 94% + 1% cyclohexane, Ciba-Geigy Batch No. 7741 was generated by injecting the test material at a rate of 60 mL/hour into an air stream which was discharged into the exposure chamber through a spray nozzle under a pressure of 2 atm. at a rate of 10 L/min.
The control animals were exposed to 60 mL/hour of ethanol 94% + 1% cyclohexane under the same conditions as decribed above.

The concentration and the particle size distribution of the aerosol in the 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 through a selectron filter of 50 mm diameter and with a pore size of 0.2 ym (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 pm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
935 +/- 49 mg/m3 (limit test)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
During the exposure period the following parameters were controlled once at half time of the study inside the inhalation cylinder: temperature (with a THERM 2104 contact thermometer, Ahlborn Messund Regeltechnik, 815 Holzkirchen, Germany), relative humidity (with a VASALA 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 the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days.
Statistics:
LC50 including 95% confidence limits are calculated by the logit model.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 000 mg/m³ air (nominal)
Exp. duration:
4 h
Mortality:
No deaths occured.
Clinical signs:
other: Dyspnoea, exophthalmos, ruffled fur, and curved and ventral body positions were reported from 2 hours to 4 days after exposure. (Sex and number of animals displaying these clinical signs not reported). All animals recovered within four days
Body weight:
No significant change throughout 14 day observation period.
Gross pathology:
Autopsy revealed “partially haemorrhages in the lungs” of treated animals. No details are given whether that means that only part of the lungs or part of the animals were affected. (Number and sex of animals not reported).

Any other information on results incl. tables

The control rats did not show any symptoms.

Particle size distribution analysis showed that approximately 80% were < 7µm.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LC50 reported to be greater than 1000 mg/cubic-meter air.
Executive summary:

In this guideline (OECD 403) comparable study, the acute (4 hour) LC50 of the test material to rats was determined to be >1000 mg/m³. 20 rast (10 male, 10 female) were exposed to the test material at a test concentration of 935 ± 49 mg/m³ in a 95% ethanol 1 % cyclohexane aerosol (nose only). No mortality was reported in the study, although adverse effects (which are not reported as treatment related) were reported in some animals. The result of the test does not meet the criteria of the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008) for the test material to be classified as acutely toxic.