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:
other: GLP compliant, comparable to guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): identification number: LF-9128 (TA 691)
- Physical state: a clear, colorless liquid
- Stability at test conditions: stable
- Storage: refrigerated (approximately 3°C).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river Breeding lab. Inc., Portage, MI
- Weight at study initiation: 225-319 gram
- Housing: individually in stainless steel cages, exposure in 1m3 glass and stainless steel chambers (Unifab, Kalamazoo, MI)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: approximately 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5
- Humidity (%): 36.2
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The animals were exposed for 4 hours to a test atmosphere generated from a single batch of the test article. The generation system consisted of a glass column packed with glass beads. The test article was delivered at a constant rate from a glass reservoir. Compressed air entered at the bottom of the glass bead column and test article entered approximately at the middle of the column. The resultant vapour entered the chamber supply air duct and was carried into the top of the chamber. The test article was completely vapourized with only a slight discolouration of the glass beads. The amount of residue on the beads was too small to measure.
The exposure was conducted in 1m3 glass and stainless steel chambers (Unifab, Kalamazoo, MI).

Analytical verification of test atmosphere concentrations:
yes
Remarks:
the test article vapour concentration was monitored by IR
Duration of exposure:
4 h
Concentrations:
5400 mg/m³
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Five male and five female Sprague-Dawley rats were assigned to a single group, which was exposed in a 1 m3 exposure chamber to a mean TAME vapour concentration of 5,400 mg/m3 for 4 hours. The rats were clinically observed immediately after removal from the chamber, approximately 2 to 3 hours after the exposure and at least once per day during the 14-day post exposure observation period. Rats were weighed before the exposure, one week later and before necropsy.

Examinations performed: clinical observations, body weights, gross necropsy.
Statistics:
Statistical analyses were used to analyse the results: calculation of standard deviations.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 400 mg/m³ air
Exp. duration:
4 h
Mortality:
No mortality was observed.
Clinical signs:
In clinical observations, rales were seen in all rats immediately following the exposure. The rales were present in 7/10 animals about 2 hours after the exposure, but 3 ¼ hours later all rats appeared normal. Redness around the nose in 7/10 rats, salivation (1/10) and wet paws (1/10) were also observed during the study but were considered incidental and unrelated to treatment.
Body weight:
All rats gained weight during the study.
Gross pathology:
Necropsy revealed external haemorrhagic lung foci in the lungs in seven rats. However, mostly these foci were comparable in size and number to control rat foci, with the exception of one female rat that had numerous foci. One male that had a diffuse red area on its lungs. Six rats had enlarged mandibular lymph nodes.

Applicant's summary and conclusion