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:
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 one test concentration, limited data on test material, no data is given on body weight development)
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further details were given.

Test animals

Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bred under SPF conditions in companies own breeding unit
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 195 - 205 g
- Housing: Males and females were segregated and kept in Macrolon cages, type 4 (9 animals to a cage)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: modified version of an apparatus described by Niessen et al., Arch. Toxicol. 20, 44-60 (1963)
- Method of holding animals in test chamber: animals were kept in PVC tubes positioned radially around the exposure chamber.
- Source and rate of air: compressed air (2 atm)
- System of generating aerosols: The liquid was injected by a motor driven syringe at a rate of 60 ml/hr.
- Method of particle size determination: The particle-size distribution in the aerosol was determined gravimetrically on Selectron-Filters, pore size 0.2 ym (Schleicher and Schuell, 8714 Feldbach, Switzerland) every hour with the aid of a "Cascade Impactor" (CT. Casella and Co. Ltd., London N.l, England).

TEST ATMOSPHERE
- Brief description of analytical method used: The aerosol was sampled on membrane filters, pore size 0.2 µm (Sartorius, Göttingen, Germany) in the immidiate vincinity of the animals hourly after the beginning of the test. The concentration of TK-10021 was determined gravimetrically.
- Samples taken from breathing zone: yes

VEHICLE
- Concentration of test material in vehicle (if applicable): 20 %. 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.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: approximately 5 % > 7 µm, 20 % 3-7 µm, 53 % 1-3 µm, 22 % < 1 µm
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric filter analysis
Duration of exposure:
4 h
Concentrations:
927 + / - 82 mg/m³, max. technically achievable concentration
No. of animals per sex per dose:
9
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: after 0-4 hrs, 24 hrs, 48 hrs, 7 days
- Necropsy of survivors performed: Yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortalitiy occured.
Clinical signs:
During the 4-hour exposure and the subsequent 7-day observation period no toxic symptoms were observed.
Body weight:
No data is given.
Gross pathology:
No substance related gross organ changes were seen.

Applicant's summary and conclusion