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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted using a method similar to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were that only male animals were used.

Data source

Reference Type:
study report
Report date:

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetramethyl orthosilicate
EC Number:
EC Name:
Tetramethyl orthosilicate
Cas Number:
Molecular formula:
tetramethyl silicate
Details on test material:
- Name of test material (as cited in study report): Tetramethoxysilane
- Substance type: Silicate
- Physical state: Liquid
No further details available

Test animals

Details on test animals or test system and environmental conditions:
- Source: Spartan Research
- Age at study initiation: No data
- Weight at study initiation: No data (80-100g when received)
- Fasting period before study: No data
- Housing: Exposure chambers were 'all-glass chambers'.
- Diet (e.g. ad libitum): Ad libitum except during exposure period
- Water (e.g. ad libitum): Ad libitum except during exposure period
- Acclimation period: yes, but no details.

- Temperature (°C), humidity (%), air changes (per hr): all controlled but no further information.
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
clean air
Details on inhalation exposure:
- Exposure apparatus: All glass chamber (10 animals per chamber).
- Exposure chamber volume: No data
- Method of holding animals in test chamber: assumed to be free in chamber
- System of generating vapour: Vapours were generated by bubbling clean, dry air through the test substance. The airflow rate through the bubbler was 10-30mlpm. The resulting vapours were diluted with laboratory air and passed directly into the chmaber. The dilution airflow rate was 14 lpm.

- Brief description of analytical method used: A probe was inserted into the side of the chamber. The other end of the probe was connected to a Miran Infrared.
- Samples taken from breathing zone: no
Analytical verification of test atmosphere concentrations:
By long-path gas infrared spectroscopy
Duration of exposure:
ca. 4 h
31, 50 and 88 ppm
No. of animals per sex per dose:
Ten males per dose
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for clinical signs and mortality were made at various times during the exposure and post-exposure period. Individual body weights were recorded for all animals prior to exposure and for all animals that survived at 2, 3, 4, 7 and 14 days post-exposure.
- Necropsy of survivors performed: yes, on 'most' animals.
- Other examinations performed: All major organs in the thoracic and abdominal cavities were observed for macroscopic abnormalities.
Probit analysis was run on mortality data to calculate the LC50.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
ca. 63 ppm
95% CL:
>= 51 - <= 78
Exp. duration:
4 h
Remarks on result:
other: Equivalent to 392.17 mg/m3
No deaths at 31 ppm, three deaths at 50 ppm, and nine deaths at 88 ppm. All deaths occurred in the first week after exposure.
Clinical signs:
other: The main clinical sign was gasping or coughing, which was observed in the two highest exposure groups. None of the animals in the low dose group showed this sign, and most of the animals in the 88 ppm group had severe gasping. The health of these animals
Body weight:
The animals exposed to 31 ppm all showed considerable weight gains by the end of the post-exposure period. All animals exposed tp 50 ppm had considerable weight losses by the second day of the post-exposure period, three of these animals died. All animals that survived the second day showed considerable weight gains by the end of the study. The single animal that survived 88 ppm recovered from an initial weight loss and gained weight by the end of the observation period.
Gross pathology:
All necropsied animals showed lung damage, the severity of which was dose-dependent. The extent of the lung damage ranged from small, discrete foci to areas covering entire lung lobes. Three of ten animals in the 50 ppm exposure group died during the 14 day post-exposure period. Three animals were sacrificed on the 14th day. The lungs of these animals were of 'good colour' and had a few areas of focal discolouration. Four animals were kept beyond the post-exposure period. One animal was sacrificed on the 28th day after exposure. This animal appeared to be healthy, and was not observed to be coughing. The lungs of this animal had a uniformly good pink colour. Necropsies were performed on the remaining animals 60 days after exposure. Discolouration was found in the lungs of all of these animals. Diffuse damage was observed in two, focal in one. No other findings reported.
Other findings:
No other findings reported.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category I
Migrated information Criteria used for interpretation of results: EU
In an acute inhalation study conducted using a protocol similar to OECD 403 and to GLP (reliability score 2), the LC50 for tetramethyl orthosilicate in Sprague-Dawley rats was 63 ppm (392.17 mg/m3). The main clinical sign observed in the post-exposure period (14 days) was gasping and coughing. Animals at the two higher exposure concentrations experienced loss of body weight. Most of the animals did not recover and died within the first week of the post-exposure period. The main macroscopic abnormality was lung damage. All animals necropsied showed lung damage. The extent of which ranged from small discrete foci to areas covering entire lobes of the lungs.