Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity 99.8%
appearance:white melting
batch 280694 from June, 28th, 1994
storage condition: refrigerated
Expiry date: June 1999

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
strain HOE:WISKf(SPF71)
Origin: Hoechst AG, Kastengrund, SPF breeding colony
age at start of the study: m/f: 8 weks
weight at the start of study: m: 180-187 g, n=5. f: 179-196 g, n=5
animal maintenance: fully air conditioned rooms, makrolon type 4 cages, soft wood granulate in groups of 5 animals
acclimatisation: 1 week under study conditions

room temp: 22 +/-3°C
relative humidity: 50 +/-20%
lighting time: 12h daily

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
rats were placed individually in cylindrical tubes and exposed to a specified gas concentration via a nose-only exposure chamber of 20l. The chambers have been tested to were shown to yield a uniform distribution of aerosols in the different breathing zones of the animals.

Norbornene was melted , maintained in a tempered oil-ath of approx. 70°C. A defined amount of air (43l/h) was drawn through the flask and diluted with additional air to provide the desired concentration. Air supply was maintained at a constant rate by means of an air-calibrated flow meter, the total amount of test atmosphere enerated was 600 l/h.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
individual measurements (mg Norbornene/l): 19.62; 30.79; 29.36; 26.59
mean values: 26.59 mg Norbornene/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
during exposure and for further 14 days animals observed with behavious check (twice daily, on weekends once daily), weighing (weekly).
Necropsy was performed on animals found dead and at the end of the observation period

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 26.59 mg/L air
Exp. duration:
4 h
Mortality:
2 male rats were found dead shortly after the end of the exposure period.
Clinical signs:
other: the animals showed irregular respiration and increased respiration rate, ruffled coat, narrowed palpebral fissures, stilted and uncoordinated gait, sunken flanks, squatting posture, lateral position and stupor. Additionally reduced placing reaction, tremb
Body weight:
body weight development was not impaired
Gross pathology:
Autopsy of the two animals found dead showed grey discoloured lungs, plethoric lungs and dark-red patches on the lungs.
Autopsy at termination revealed red paatches on lungs in male rats and red spots on the lungs of one female animal. Necropsy of the other animals did not show any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Norbornene showed an inhalative toxicity of L50 >26.59 mg/l when appliead as aerosol.
Executive summary:

In an acute inhalation toxicity study, norbonene was applied as an aerosol at 26.59 mg/l air to groups of 5 young adult male and female Wistar rats in an nose only type of experiment for a period of 4h. The animals were observed for 14d.

Clinical symptons were reversible within two days. Two male rats dies shortly after exposure.

The combined LC50 > 26.59 mg/l air.