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Administrative data

Description of key information

In an acute oral toxicity study that was comparable to the now deleted OECD Test Guideline 401, but not to GLP (reliability score 2) the LD50 was at least 3500 mg/kg bw for male and female rats (ASTA Pharma AG, 1988).

In an inhalation study conducted to OECD Test Guideline 403 and to GLP (reliability score 1) the LC50 for 4-hour aerosol exposure to trimethoxy(octyl)silane was 7.5 and 1.9 g/m3 for males and females, respectively (TNO-CIVO, 1990).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30.06.1987 to 31.07.1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No information on the purity of the TS, only two doses tested.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: Males: 26-29 weeks; Females: 27-29 weeks
- Weight at study initiation: Males: 332-429 g; Females: 212-247 g
- Fasting period before study: 16 hours
- Housing: Individually in Makrolon cages Type II
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 2
- Humidity (%): 55 15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Not given but study period was 30.06.1987 to 31.07.1987
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.11 ml/kg
Doses:
3236 and 4752 mg/kg
No. of animals per sex per dose:
Ten
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days for low dose and 21 days for high dose
- Frequency of observations and weighing: Behaviour and general condition were noted for the first 4-8 hours after dosing and then once daily. Mortality was checked twice daily. Body weights were recorded at the beginning and also 7, 14 and 21 days after administration.
- Necropsy of survivors performed: yes, a gross necropsy was performed on all animals. Macroscopic examination included external appearance, body orifices, body cavities and their contents.
Statistics:
None. LD50s estimated.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 5 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 3 500 mg/kg bw
Based on:
test mat.
Mortality:
See Table 1. Deaths occurred between day 4 and 17 after administration.
Clinical signs:
See Table 2. Following a dose of 3236 mg/kg bw there were coordination disturbances, piloerection, chromodacryorrhea, increased salivation and red nasal discharge. Following a dose of 4752 mg/kg bw there was additionally decreased muscle tone, loss of righting reflexes and increased diuresis. Individually also, tremor, vocalisation on handling, lacrimation, opacity of the cornea and green discoloured urine occurred. The development of toxic effects was protracted, with coordination disturbances detected after two hours, and all other symptoms from days 2-5. In the high dose group the effects were still apparent after 14 days, so the observation period was extended until they disappeared (three weeks).
Body weight:
Body weights were reduced following administration of both doses. In the highest dose group five animals were watered from day 2 or 3 because of their bad general condition, however the food intake was severely decreased. This lead to a severe decrease in body weight.
Gross pathology:
At necropsy of the deceased female animals the small intestine was filled with a red liquid. The deceased male animals showed cryptorchism (incidental finding).

Table 1 Mortality data

 Dose group (mg/kg bw)     Mortality rate     Time of death
   x/n  %  Hours post application  Days post application
             Males
 3236  0/5  0    
 4752  2/5  40    16 and 17
             Females
 3236  0/5  0    
 4752  3/5  60    Two on day 14 and one on day 8

Table 2 Clinical signs of toxicity

  Symptom Dose (mg/kg bw)          
   Male 3236  Male 4752  Female 3236  Female 4752
 Coordination disturbance 3  3  3  3
 Slight tremor    1    1
 Decrease of muscle tone AP    1    3
 Loss of righting reflex LP/DP    1    3/3
 Lacrimation        1
 Chromodacryorrhea    2  1  2
 Increased salivation  1    1  2
 Red nasal discharge  1  2  1  2
 Strenuous respiration    1    3
 Piloerection  1  3  4  4
 Diuresis/green urine        1/1
 Vocalisation on handling    1    
 Opacity of the cornea        1
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study that was comparable to the now deleted OECD 401, but not to GLP (reliability score 2) the LD50 was at least 3500 mg/kg bw for male and female rats. Following a dose of 3236 mg/kg bw there were coordination disturbances, piloerection, chromodacryorrhea, increased salivation and red nasal discharge. Following a dose of 4752 mg/kg bw there was additionally decreased muscle tone, loss of righting reflexes and increased diuresis. Individually also, tremor, vocalisation on handling, lacrimation, opacity of the cornea and green discoloured urine occurred. The development of toxic effects was protracted, with coordination disturbances detected after two hours, and all other symptoms from days 2-5. All symptoms disappeared by day 21 of the observation period.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 500 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
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
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
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.
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

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
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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
3 900 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study that was comparable to the now deleted OECD Test Guideline 401, but not to GLP (reliability score 2) the LD50 was at least 3500 mg/kg bw for male and female rats (ASTA Pharma AG, 1988). Following a dose of 3236 mg/kg bw there were coordination disturbances, piloerection, chromodacryorrhea, increased salivation and red nasal discharge. Following a dose of 4752 mg/kg bw there was additionally decreased muscle tone, loss of righting reflexes and increased diuresis. Individually, tremor, vocalisation on handling, lacrimation, opacity of the cornea and green discoloured urine occurred in addition. The development of toxic effects was protracted, with coordination disturbances detected after two hours, and all other symptoms from days 2-5. All symptoms disappeared by day 21 of the observation period.

In an inhalation study conducted to OECD Test Guideline 403 and to GLP (reliability score 1) the LC50 for 4-hour aerosol exposure to trimethoxy(octyl)silane was 7.5 and 1.9 g/m3 for males and females, respectively (TNO-CIVO, 1990). The combined LC50 was 3.9 g/m3. Clinical effects included reduced body weights, slow breathing, piloerection and signs of ataxia.  There were no dermal data. However, the skin irritation study (ASTA Pharma AG, 1987a) did not reveal any systemic effects.

In the acute inhalation study (TNO-CIVO, 1990), the test atmospheres contained a mixture of vapour and aerosol, but based on the vapour pressure of the substance (2.1 Pa at 25°C), it is likely that the majority of the test atmosphere was aerosol.


Justification for classification or non-classification

Based on the available data, trimethoxy(octyl)silane does not need to be classified for acute toxicity (lethality) following a single oral exposure according to Regulation (EC) No 1272/2008.

Following oral exposure there were clinical signs (e.g. coordination disturbances, loss of muscle tone, ataxia). However these were observed only at dose levels far in excess of the maximum dose used according to current guideline standards therefore no classification is applied for this endpoint.

For the inhalation route, it is not considered appropriate to classify for acute toxicity as the observed effects are due to exposure to aerosol droplets rather than to systemic availability of the test substance. Inhalation of aerosol droplets is not a relevant route of exposure for this substance.