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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:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Only 7 day observation period, but no individual data were provided; air flow rate given for spray nozzle (nose-only exposure). Test concentration is below limit dose, but no higher doses could be technically achieved. Little details on test item.
GLP compliance:
no
Remarks:
Study pre-dates GLP requirements.
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited (Toxicology/Pathology).
- Age at study initiation: 8 to 9 weeks old.
- Weight at study initiation: 200 to 210 g.
- Fasting period before study: Not reported.
- Housing: 9 animals per cage, males and females were segregated and kept in Macrolon cages, type 4.
- Diet (e.g. ad libitum): Not reported.
- Water (e.g. ad libitum): Not reported.
- Acclimation period: Not reported.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.
- Humidity (%): Approximately 50%.
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): Not reported.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Remarks:
Test animals were kept in separate PVC tubes positioned radially around the exposure chamber. These tubes were so designed that only the animals' snouts were exposed to the aerosol.
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A modified version of an apparatus described by Niessen et al. [Arch. Toxicol. 20, 44-60 (1963)].
- Exposure chamber volume: Not reported.
- Method of holding animals in test chamber: The test animals were kept in separate PVC tubes positioned radially around the exposure chamber. These tubes were so designed that only the animal's snouts were exposed to the aerosol.
- Source and rate of air: Not reported.
- Method of conditioning air: Membrane Filters, pore size 0.2 µm (Satorius, 34 Göttingen, Germany).
- System of generating particulates/aerosols: A 20% suspension in ethanol of TK 10047 was sprayed into the exposure chamber by means of a pressure nozzle. The liquid was injected by a motor-driven syringe at a rate of 60 mL/h into a stream of compressed air (2 atm.) flowing through a spray nozzle at a rate of 10 L/min. The aerosol mist thus produced was discharged into the exposure chamber. The output of the spray device and the dimensions of the inhalation chamber are so adjusted to each other that the solvent evaporates on the way from the nozzle orifice to the rat containers.
- Method of particle size determination: The particle-size distribution in the aerosol was determined gravimetrically on Selectron-Filters, pore size 0.2 µm (Schleicher and Schuell, 8714 Feldbach, Switzerland) every hour with the aid of a "Cascade Impactor" (C.T. Casella and Co., Ltd., London N.l, England).
- Treatment of exhaust air: Not reported.
- Temperature, humidity, pressure in air chamber: Not reported.


TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of TK 10047 was determined gravimetrically.
- Samples taken from breathing zone: Yes.


VEHICLE
- Concentration of test material in vehicle: 20%
- Justification of choice of vehicle: Not reported.
- Lot/batch no. (if required): Not reported.
- Purity: Not reported.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 82% of the material had a particle size of less than 7 micrometer.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Not reported.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The concentration of TK-10047 was determined gravimetrically.
Duration of exposure:
4 h
Remarks on duration:
None
Concentrations:
0.590 mg/L (Concentration as reported in the study report: 590 ± 72 mg/m3; average aerosol concentration, gravimetrically determined)
No. of animals per sex per dose:
9 animals per sex.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days.
- Frequency of observations and weighing: Not reported.
- Necropsy of survivors performed: Yes.
- Other examinations performed: Clinical signs and mortality were observed.
Statistics:
Not reported.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 590 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: 82% of particles < 7 micrometer; each 2 males and females died within 24h. Surviving animals recovered within 48h.
Mortality:
Each two males and two females died within 24h after exposure.
Clinical signs:
After the 4-hour exposure the rats showed tachypnoea, asynchronisms of the extremities, lateral or ventral position and apathy. The surviving animals had recovered within 48 hours.
Body weight:
Not reported.
Gross pathology:
Hemorrhage in the lungs and congested organs were observed in dead animals.  No substance related gross organ changes were seen in animals killed at the end of observation period of 7 days.
Other findings:
- Organ weights: Not reported.
- Histopathology: Not reported.

- Other observations: Not reported.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU