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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
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

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:
EC Number:
EC Name:
Cas Number:
Molecular formula:

Test animals

Details on test animals or test system and environmental conditions:
- Source: Harlan Sprague-Dawley Inc
- Age at study initiation: 51 to 59 days old.
- Weight at study initiation: 136-273 g
- Fasting period before study: No data
- Housing: Five per sex in stainless steel wire-mesh cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data

- Temperature (°C): 18-22
- Humidity (%): 40-62
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27.08.1988 To: 28.09.1988

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
other: unchanged (no vehicle)
Details on inhalation exposure:
- Exposure apparatus: For the static exposure the test substance was placed as received in an open tray at the top of the sealed 120 l chamber and the vapour was allowed to achieve equilibrium. The animals were then placed into the chamber for either a 10 minute or one hour period. For the dynamic exposures, liquid test substance was metered from a syringe pump into a heated evaporator. The resulting vapour was carried into the chamber by an inlet air stream. The animals were then placed into the chamber for either a one or four hour period.
- Exposure chamber volume: 120 litre (static exposure) and 900 litre (dynamic exposure)
- Method of holding animals in test chamber: Animals were housed individually in wire-mesh cages; 26 x 18.5 x 18 cm (static) and 21 x 12.5 x 18 cm(dynamic), inside the larger chamber.
- Source and rate of air:
- Method of conditioning air: No data
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: No data

- Brief description of analytical method used: The concentration of methanol, a reaction product of trimethoxysilane and water, was determined during the exposure. Chamber concentration analysis was assessed by a gas chromatograph equipped with a flame ionization detector to monitor trimethoxysilane and methanol vapor concentrations in the chambers.  The nominal concentrations were determined by dividing the total weight of the test material delivered by the total volume of air which passed through the chamber during the exposure period. 
- Samples taken from breathing zone: No
Analytical verification of test atmosphere concentrations:
gas chromatograph equipped with a flame ionization detector
Duration of exposure:
4 h
The target concentrations for the static exposures was a saturated vapour. For the one hour dyamic exposure mean concentrations achieved were: 643, 342, 155 and 68 ppm (mean methanol concentrations were 173, 60, 19 and 9 ppm). For the four hour exposure period mean concentrations achieved were 166, 71, 39 and 19 ppm (mean methanol concentrations were 66, 7 and 9 ppm, excluding highest dose level)
No. of animals per sex per dose:
Control animals:
Details on study design:
 - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for signs of toxic and pharmacologic effects on the day of exposure and daily following exposure.  Body weights were recorded prior to exposure and on postexposure Days 7 and 14.
- Necropsy of survivors performed: yes, on all animals
- Other examinations performed: Lungs and livers were collected, fixed and stained, and examined microscopically.
Statistical procedures: The mean and standard deviation of the body weights, body weight changes, and exposure concentrations were calculated.  No statistical comparisons were made.  The 4-hr LC50 value was determined by a modified method of Finney's (1964) probit analysis for males, females, and the combined sexes.

Results and discussion

Effect levelsopen allclose all
Key result
Dose descriptor:
Effect level:
60 ppm
95% CL:
>= 45 - <= 80
Exp. duration:
4 h
Key result
Dose descriptor:
Effect level:
81 ppm
95% CL:
>= 54 - <= 122
Exp. duration:
4 h
Key result
Dose descriptor:
Effect level:
42 ppm
95% CL:
>= 29 - <= 62
Exp. duration:
4 h
Under static conditions all animals died during or within two hours of exposure for 10 minutes or one hour. Under dynamic conditions there were deaths at all concentrations, except 68 ppm (1-hour) and 19 ppm (4-hour) groups. Deaths occurred primarily on post-exposure days six to 13.
Clinical signs:
other: Clinical signs observed during or following the static exposure were: CNS excitation and breathing difficulties, white residue covering eyes, nose and mouth. Under dynamic conditions: 166 ppm: Male - day of exposure: blepharospasm, abdominal breathing, de
Body weight:
Losses in body weight were observed in animals from all one hour and four hour groups during both postexposure weeks.
Gross pathology:
In the static exposure group gross lesions included: mottled red discolouration of the lungs, dark purple discolouration of the liver and clear fluid in the trachea and thoracic cavitiy. Microscopic examination of the lungs from the 10 minute exposure group revealed congestion, oedema and fibrin formation, and in some rats there was exfoliation of the bronchoilar epithelial cells. In the dynamic groups, no gross lesions were reported for either males or females in any groups.  Potential target organs: Lung dysfunction.
Other findings:
The mean (+/- SD) analytical concentrations of trimethoxysilane in the exposure chamber for the 4-hour study were 166 (+/- 14), 71 (+/- 15), 39 (+/- 14), and 19 (+/- 4) ppm.  The mean (+/- SD) methanol concentrations for the 71, 39, and 19 ppm trimethoxysilane exposures were 66 (+/- 54), 7 (+/- 2.5), and 9 (+/- 2) ppm, respectively.  The methanol concentration for the 166 ppm trimethoxysilane exposure was 25 ppm after 51 min of exposure and, thereafter, less than the estimated minimum detection limit of 5 ppm.  The analytical/nominal trimethoxysilane concentrations for these exposures were 0.69, 0.66, 0.49, and 0.84, respectively.  Mean temperature during the 4-hour exposures ranged from 21-24 deg C.  Mean percent relative humidity (+/- SD) during the 4-hour exposures was 37  (+/- 1), 54 (+/- 1), 46 (+/- 2), and 46 (+/1) for 166, 71, 39, and 19 ppm trimethoxysilane, respectively.

Any other information on results incl. tables

Table 1 Summary of mortality data for the dynamic exposure groups.

 Concentration of trimethoxysilane (ppm) Duration (hour)   Sex  Deaths/total
 643  1  5/5
 643  1  F  5/5
 342  1  M  5/5
 342  1  F  5/5
 155  1  M  2/5
 155  1  F  3/5
 68  1  M  0/5
 68  1  F  0/5
 166  4  M  5/5
 166  4  F  5/5
 71  4  M  2/5
 71  4  F  5/5
 39  4  M  0/5
 39  4  F  1/5
 19  4  M  0/5
 19  4  F  0/5


Table 2 Summary of mean weight changes in dynamic exposure groups

 Concentration of trimethoxysilane (ppm)*  Mean body weight change (SD) (g)         
      One hour exposure Four hour exposure    
   Day 7  Day 14  Day 7  Day 14
1 -55 (7)  -  -63 (8)  -
2  -52 (3)  -27 (7)  -54 (20)
3  -41 (23) -2 (41)   3 (3)  -10 (36)
4  3 (9)  27 (6)  -3 (4)  13 (34)
 1  -34 (8)  -  -44 (4)  -
 2  -38 (1)  -  -22 (18)  -
 3  -37 (8)  -42 (25) 2 (2)   -4 (35)
 4  -7 (18)  4 (28)  3 (4)  22 (4)

*One hour exposure: Groups 1, 2, 3, and 4 concentrations of 643, 342, 155 and 68 ppm, respectively.

Four hour exposure: Groups 1, 2, 3, and 4 concentrations of 166, 71, 39 and 19 ppm, respectively.

Applicant's summary and conclusion

Interpretation of results:
Category 1 based on GHS criteria
Criteria used for interpretation of results: EU
In a well conducted acute inhalation toxicity study conducted using a protocol comparable to OECD Test Guideline 403 and in accordance with GLP, the combined LC50 value for the 4-hour exposure was 60 ppm (ca. 300 mg/m3). There was no significant difference in LC50 values between male and female rats.
Executive summary:

In a well conducted acute inhalation toxicity study (reliaility score 1) conducted using a protocol of which elements were comparable to OECD Test Guideline 403 and in accordance with GLP, a series of inhalation exposures was conducted in which five Sprague-Dawley rats/sex were exposed once to trimethoxysilane vapour by static (for 10 or 60 minutes) or dynamic (for 1 or 4 hours) generation methods, and then observed for 14 days. Since the four hour dynamic conditions are most like the OECD test guideline recommendations only results from this part of the study are presented in this summary. The exposure concentrations in this group were 19, 39, 71 and 166 ppm.

There were deaths at all concentrations, except in the 19 ppm groups. Deaths occurred primarily on post-exposure days 6 to 13. Males in the 166 ppm group had blepharospasm, abdominal breathing, decreased motor activity, ataxia,  slow surface-righting reflex on the day of exposure. One rat on postexposure days 9-12 and one on days 11 - 13 had unkempt fur, decreased breathing rate and motor activity. Females in the 166 ppm group had blepharospasm, periocular wetness, decreased breathing and motor activity. Signs during postexposure days 5 -9 included unkempt fur, audible respiration, decreased respiration rate and motor activity. Males of the 71 ppm group had blepharospasm, abdominal breathing, decreased motor activity, ataxia and a slow surface righting reflex on the day of exposure. Signs on post-exposure days 9-13 included unkempt fur, decreased respiration rate and decreased motor activity. In females periocular wetness, abdominal breathing and decreased motor activity were observed during exposure, and unkempt fur and decreased motor activity on postexposure days 10 -14. Similar clinical signs were also observed in the 39 ppm group. Losses in body weight were observed in animals from all one hour and four hour groups during both postexposure weeks. There were no abnormal findings in the gross necropsy examination.

The LC50 for the 4 -hour exposure was determined to be 60 (45 to 80) ppm (ca. 300 mg/m3); there was no significant difference in LC50 values between male and female rats.