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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:
9 April 2004 - 23 June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Mass median aerodynamic diameter / Geometric st. dev. not reported.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Age at study initiation: 9 weeks at experimental start
- Weight at study initiation: females 199.4-208.2 g, males 295-310 g
- Housing: wire-mesh cages
- Diet: certified rodent chow, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: 450 litres
- Method of holding animals in test chamber: The animals were positioned within stainless steel exposure caging specifically designed for use in the 450 litre chamber (two levels of 10 wire mesh cages).
- Source and rate of air: Nash Air Compressor (Model/Size: AL-574), air sourced from building air supply
- Method of conditioning air: Conditioned building air was passed through HEPA and activated charcoal filters before delivery to the chamber. The compressed air was passed through a series of filters to remove contaminants (Matheson model: 460/461 and Balston model 100-18-DX and 100-18-BX) prior to use in test atmosphere. Chamber atmosphere consisted of a dilution air stream and a octamethyltrisiloxane vapour/carrier stream. The dilution air stream was building-conditioned air (i.e. warmed and humidified) passed through activated carbon and HEPA filters. The carrier air stream was compressed air passed through a series of particulate filters prior to use in vapour generation.
- System of generating particulates/aerosols: Generation of test article vapour concentration was performed using a heated stainless steel J-tube containing a column of stainless steel beads. Test article was metered from a reservoir into the J-tube using a pump. Compressed air flowed through the J-tube at a controlled rate of 34.8 l/minute. The carrier/vapour mixture passed from the J-tube to the inlet port at the top of the exposure chamber. Just prior to entering the exposure chamber, the carrier/vapour mixture combined with chamber supply air (dilution air) and was diluted to the target chamber concentration as it enters the exposure chamber.
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: The exposure chamber was operated under dynamic conditions with regard to airflow, temperature, relative humidity and pressure. Chamber temperature was maintained within the range of 22.1-25.8°C. Chamber relative humidity was maintained within the range of 31.7%-46.6%, Chamber airflow, temperature and percent relative humidity were monitored continuously and recorded at approximately thirty-minute intervals.

TEST ATMOSPHERE
- Brief description of analytical method used: Test atmosphere oxygen content was measured once during the exposure period. The test article reservoir weight was determined pre- and post-exposure. These data, along with the chamber airflow rate and the vapour generation time, were used to calculate a nominal chamber concentration of test article. Chamber atmosphere was analysed using a Varian 3400 gas chromatograph equipped with a flame ionization detector (GC/ID) to determine the actual chamber concertation of test article. The concentration of test article in the chamber atmosphere during exposure period was evaluated approximately every 30 minutes. A continuously purged sample line was used to transfer a sample of the chamber atmosphere to the GC/FID for analysis.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Remarks on duration:
plus one 20 minute chamber equilibration time
Concentrations:
Measured 2350 ppm (22.6 mg/l)
Nominal 2448 ppm (23.5 mg/l)
No. of animals per sex per dose:
5 male, 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Mortality and morbidity were observed twice daily during the week and once daily on weekends. Following the exposure, animals were evaluated once daily for clinical signs. Individual body weights were collected prior to exposure for randomization. Following randomization, body weights were recorded on day 1 (prior to exposure), day 8, and day 15 (prior to terminal sacrifice).

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Complete gross pathology was carried out, no tissues were saved.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 22.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no mortalities.
Clinical signs:
other: There were no clinical signs.
Body weight:
All body weights and weight gains were considered normal for both sexes.
Gross pathology:
There were no macroscopic abnormalities.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An LC50 value of >22.6 mg/l (analytical) was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.