Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08.01.1990 to 22.02.1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Degussa Silane Si 108
- Substance type: Alkoxysilane
- Physical state: Colourless liquid
- Stability under test conditions: No data
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wiga, Sulzfeld, FRG.
- Age at study initiation: 7-11 weeks
- Weight at study initiation: 260-170 g
- Fasting period before study: No data
- Housing: In between exposures in suspended stainless steel cages (5 animals/cage), and during exposure housed individually
- Diet (e.g. ad libitum): Ad libitum (except during exposure when food was not available)
- Water (e.g. ad libitum): Ad libitum (except during exposure when food was not available)
- Acclimation period: From arrival to start of study

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

IN-LIFE DATES: From: 08.01.1990 to 22.02.1990

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
other: whole body for first part of study and nose-only for second part.
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body: horizontally placed, all glass cylinder, separated from other animals by a perforated stainless steel plates. Ports in the middle and at the end of the cylinder allowed sampling of the test substance. Nose-only: nose-only inhalation chamber type 8132 P2. Only the nose of the rats was protruding into the exposure chamber.
- Source and rate of air: No information on source. Rate for whole body exposure 10 l/min, for nose
- System of generating particulates/aerosols: the test atmosphere was generated by bubbling the total flow of heated air through the heated test substance. In this way the air flow became saturated with test substance. Since the concentration obtained in this way was not sufficiently high, test atmospheres for the other concentrations were generated in a different way. A sample of test substance was poured into a flask. A roller pump passed metered amounts of the test substance from the flask to a Lee 150H nebuliser connected at the top of the chamber. The air volume through the nebuliser was at maximum. The generated aerosol was diluted with clean air from the compressed air system. The aerosol was directed downwards through the mixing chambers towards the noses of the animals.
- Method of particle size determination: 11-stage cascade impactor.
- Treatment of exhaust air: Passed out from the bottom of the chamber - no further details .
- Temperature, humidity, pressure in air chamber: Whole body: 19.8 ±0.3oC, 80 ±4%, slight negative pressure. Nose-only: 18.2 oC, 69%, slightly positive pressure.

TEST ATMOSPHERE
- Brief description of analytical method used: The actual mass concentration of the test substance in the test atmosphere was determined each hour by means of gas chromatography.
- Samples taken from breathing zone: no data
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Mean actual concentrations: 0.9, 2.36, 2.53 and 6.2 g/m3.
Corresponding nominal concentrations: 3.5, 9.8, 15.4 and 27.6 g/m3.
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were visually inspected during the exposure period, and once daily during the observation period. Body weights were recorded just prior to exposure and at days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the observation period, all surviving rats were killed and examined for gross pathological changes.
Statistics:
The LC50 was calculated using Probit analysis.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
7.5 other: g/m3
Based on:
test mat.
95% CL:
>= 4.3 - <= 29.7
Exp. duration:
4 h
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
1.9 other: g/m3
Based on:
test mat.
95% CL:
>= 1 - <= 3.1
Exp. duration:
4 h
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.9 other: g/m3
Based on:
test mat.
Exp. duration:
4 h
Mortality:
See Table 1. All deaths occurred within days 1-3.
Clinical signs:
other: During exposure to 0.9 g/m3 animals showed hunched appearance, piloerection and mostly closed eyes. Breathing patterns were superficial and irregular during the first hour of exposure. Then, breathing patterns became more regular concomitant with a decrea
Body weight:
All four surviving rats exposed to 6.2 g/m3 showed severe body weight reduction seven days after exposure. However, body weight gain was observed 14 days after exposure in three out of four rats. Exposure to 0.9 g/m3 resulted in body weight gain reduction in male rats 14 days after exposure, and in decreased body weight or reduced body weight gain in female rats 7 and 14 days after exposure. Body weight gain of the other survivors exposed to 2.53 or 2.36 g/m3 was generally not affected by exposure.
Gross pathology:
At autopsy, dark-red discoloured, and sometimes swollen or darkly spotted, and/or edematous lungs were found in animals that died, or were killed in extremis after exposure to 6.2 g/m3. Furthermore, grey-white spots were observed on the lung lobes of three female rats. Exposure to 2.53 g/m3 revealed rusty-brown discoloured lungs. Red discoloured lungs were found in rats exposed to 2.36 g/m3. In the other rats that were killed in extremis no abnormalities were observed. In all surviving rats autopsied at the end of the 14-day observation period, no abnormalities were found, except for spotted lungs in one male exposed to 6.2 g/m3.
Other findings:
None

Any other information on results incl. tables

The 50% accumulation point for all four distributions was around 2.4 µm. All distributions showed a similar pattern: about 60% (exposure to 6.2 g/m3) to 89% (exposure to 0.9 g/m3) of the particles were between 1.8 and 3.4 µm in diameter.

Table 1 Summary of concentrations and mortality data

Group   Concentration (g/m3)     Mortality    
  Actual  Nominal  Males (number tested/deaths) Female (number tested/deaths)
 0.9 ± 0.32 3.5   5/0  5/0
 6.2 ± 0.6  27.6 5/1  5/5
 2.53 ± 0.64 15.4  5/0  5/4
 2.36 0.31  9.8  5/1  5/3

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In an inhalation study conducted to OECD 403 and to GLP (reliability score 1) the LC50 for trimethoxyoctylsilane was 7.5 and 1.9 g/m3 for males and females, respectively. The combined LC50 was 3.9 g/m3. Clinical effects included reduced body weights, slow breathing, piloerection and signs of ataxia.