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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:
1991-12-20 to 1992-02-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Manston, Kent, UK
- Age at exposure initiation: eight to ten weeks
- Weight at study initiation: male rats weighed 226 to 245 grams and female rats weighed 214 to 237 grams
- Housing: five animlas per cage (sexes separate) in polypropylene cages with saw dust bedding
- Diet: Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited Witham, Essex, U.K., ad libitum)
- Water: Drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 40- 68
- Air changes: 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE
The test material was aerosolised using a glass concentric jet nebuliser (Radleys, Sawbridgeworth, Herts.) located at the top of the exposure chamber. The nebuliser was connected to a glass syringe attached to a modified infusion pump, which provided a continuous supply of test material under pressure, and to a metered compressed air supply.Compressed air was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 µm before it was introduced to the nebuliser.
The cylindrical exposure chamber has a volume of approximately 30 litres. The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump and the air flow rate through the chamber. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.

EXPOSURE PROCEDURE
Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and
sealed by means of a rubber '0' ring. Only the noses of the animals were exposed to the test atmosphere. A single group of ten rats (five males and five females) was exposed to an atmosphere of the test material for aperiod of four hours. A target concentration of 5 mg/L was used for the exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
10.17 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
All animals were observed, for clinical signs, at hourly intervals during the exposure, one hour after termination of the exposure and subsequently once daily for 14 days. Any deaths or evidence of overt toxicity were recorded at each observation. At the end of the 14 day observation period, the animals were killed by intravenous overdose of sodium pentobarbitone. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 10.17 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortalities occurred
Clinical signs:
other: Wet fur was commonly noted during the exposure period and, on removal from the chamber additional signs of hunehed posture, piloerection, ataxia and oeeasional body tremors were noted. One female showed red/brown stains around the snout. One hour after co
Body weight:
Expected bodyweight development was noted in all animals throughout the study.
Gross pathology:
At necropsy, abnormalities were noted on the lungs of several animals including areas that were pale, dark, raised, hardened or with a grey diseolouration. Some animals also showed dark foci. No other abnormalities were detected in animals at necropsy.
Other findings:
none

Applicant's summary and conclusion