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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:
2011-08-02 to 2012-02-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
07 September 2009
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
Commission Regulation (EC) No 440/2008 of 30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, NIEDERLANDE
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 10 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study:
- Housing: Single housing or up to 5 animals
- Diet : Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland
- Water : Tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 30 – 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 60 (glass-steel construction, BASF SE)
- Exposure chamber volume: 90 L
- Method of holding animals in test chamber: Animals were restrained in glass tubes and their snouts projected into the inhalation system.
- Source and rate of air: Compressed air is produced by an oil-free compressor (HT 6, Josef Mehrer GmbH & Co KG, Germany). For this purpose, air is filtered by an inlet air strainer and introduced into the compressor. After passed through an second ultra filter (SMF 5/3, 108 mm, Donalson), the compressed air (15 bar) is stored in a storage of 1500 or 5000 L. The compressed air is conducted to the labs via pipes, where the pressure is reduced to 6 bar.
- Method of conditioning air: Central air conditioning system provides cold air of about 15°C. This cold air will pass through an activated charcoal filter, be adjusted to room temperature of 20 to 24°C and pass through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air is used to generate inhalation atmospheres.
- System of generating vapour: The vapor was generated by supplying amounts of the test substance to the heated vaporizer by means of the pump. The vapors that developed were taken up by the supply air and passed into the exposure system after mixing with dilution air inside the mixing vessel.
- Method of particle size determination:
- Treatment of exhaust air: The exhaust air is filtered and conducted into the exhaust air of the building.
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: For the quantitative determination of the vapor concentration, a gas chromatographic method method was used.
- Samples taken from breathing zone: yes, immediately adjacent to the animals' noses at a separate spare port

CLASS METHOD
- Rationale for the selection of the starting concentration: The selection of the concentration for the test group was based on the limit test, OECD Guidelines, method 403; Commission Regulation (EC) No 440/2008 and Environmental Protection Agency (EPA) guidelines because from the available information concerning the test substance no pronounced inhalation toxicity was expected.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The nominal concentration was calculated from the amount of test substance dosed and the supply air flow.
Duration of exposure:
4 h
Concentrations:
22.007 mg/L (measured)
No. of animals per sex per dose:
Five male and five female rats were used for the test group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights once during the acclimatization period, shortly before exposure (day 0) and at least on days 1, 3 and 7, and before the sacrifice of the animals at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, organ weights, pathology
Statistics:
Binomial test

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 22.007 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No lethality occurred at the tested concentration of 22.007 mg/L during the study period of 14 days.
Clinical signs:
No abnormalities were detected in the animals during the post exposure observation period from study day 2 onwards.
Body weight:
The mean body weights of the animals decreased during the first post exposure observation day and increased from study day 3 onward.
Gross pathology:
No gross pathological abnormalities were detected during the necropsy in the animals at the termination of the study.

Applicant's summary and conclusion