Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material


Test animals

Details on test animals and environmental conditions:

- Source: Charles River Laboratories, 401 S. New Hope rd., Raleigh, NC 27610

- Age at study initiation: ca. 9 weeks

- Weight at study initiation: Females: 218.2-226.2 g, Males: 311.9-351.7 g

- Housing: Individually housed in suspended wire-mesh cages during quarantine/acclimation period and during the in-life portion of the study.

- Diet: Certified Rodent Chow #5002, ad libitum, except during exposure

- Water: Municipal water, further purified by reverse osmosis, ad libitum, except during exposure

- Acclimation period: 7 days


- Temperature (°C): 19-25

- 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
other: not applicable
Details on inhalation exposure:

- Exposure apparatus: A Rochester - type, stainless steel and glass, whole body chamber.

- Exposure chamber volume: 450 litres

- Method of holding animals in test chamber: The animals were positioned in stainless steel exposure caging (two levels of 10 wire mesh cages).

- Source and rate of air: The source of air was a Nash Air Compressor (Model/size AL-574) The test article was metered from a reservoir under nitrogen head space, into the J tube using a Fluid Metering Incorporated pump. Compressed air flowed through the J-tube at a controlled rate of ca 30L/min. 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 conditioning air: The compressed air which acted as a carrier, was passed through a series of filters to remove contaminants prior to use in test atmosphere generation. Conditioned building air was passed through HEPA and activated charcoal filetrs before delivery to the chamber. Moisture was added as necessary to maintain relative humidity within the required range.

- 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.

- 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 21.9-26.4°C, humidity within 37.5-60%. Each exposure chamber contained a temperature/humidity sensor, which was monitored.


- Brief description of analytical method used: 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. In the presence of moisture, methyltrimethoxysilane has the potential to hydrolyze, leading to the formation of methyl alcohol. Therefore, actual chamber concentrations of both test article and methyl alcohol were analyzed using a Varian 3400 gas chromatograph equipped with a flame ionization detector. The concentration of test article and methyl alcohol in the chamber atmosphere during the exposure period was evaluated approximately once every 30 minutes.

- Samples taken from breathing zone: yes

CLASS METHOD (if applicable)

- Rationale for the selection of the starting concentration: The limit test concentration was selected based on the lower explosive level of the material.
Analytical verification of test atmosphere concentrations:
Duration of exposure:
6 h
8000 ppm (nominal), 7605 ppm (analytical)
No. of animals per sex per dose:
5M/ 5F
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were carried out daily and body weights were recorded just prior to exposure on day 1, again on day 8 and prior to terminal sacrifice on day 15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Signs of toxicity including, but not limited to, changes in the skin and fur, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, motor activity and behaviour pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All animals were euthanized on day 15 and subjected to a complete gross pathology examination (no tissues were saved).
The mean chamber concentration of the test substance was calculated along with the standard deviation. Additionally, chamber environmental conditions, including temperature, humidity and airflow were monitored continuously and recorded ca. every 30 min. Mean and standard deviation were calculated for each of these parameters.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
> 7 605 ppm
Based on:
test mat.
Exp. duration:
6 h
No mortalities reported.
Clinical signs:
other: Urine staining, discoloured urine, fecal staining, head and muzzle soiling, with all females returning to normal by post exposure day 4. Four of the 5 males were reported normal by post exposure day 5, and all males were normal by post exposure day 10.
Body weight:
Body weights and body weight gains were within normal limits over the duration of the study for all females. Two of the five males demonstrated weight loss during the first week post-exposure, with a return to normal weight gain during the second week.
Gross pathology:
Necropsy findings included urinary bladder calculi and kidney foci in both sexes, an enlarged kidney in one male, and abcessed prostrate glands in two males. Urinary tract and prostate disease was attributed to urolithiasis of uncertain primary aetiology; a direct role for the test article in the formation of urinary calculi could neither be confirmed nor denied as a result of this study.
Other findings:
No other effects reported.

Any other information on results incl. tables


Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
The acute inhalation LC50 value of > 7605 ppm (42.1 mg/L) for rats was determined in a reliable study conducted according to a test appropriate protocol, and in compliance with GLP.