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Description of key information

In an acute oral toxicity study conducted to the now deleted OECD 401 and to GLP (ASTA Medica AG, 1992a) the LD50 for triethoxy(octyl)silane was at least 5110 mg/kg bw in rats. Signs of intoxication were slight to moderate hypokinesia, diarrhoea and piloerection in male and female rats. In addition, individual female animals showed coordination disturbances, stilted gait, red encrusted snout, strenuous respiration, sunken sides and vocalisation on handling. In general symptoms were observed on days two to three. In one female, first symptoms appeared 160 minutes after administration. In individual females signs of toxicity lasted for 14 days or until death. In male animals symptoms lasted at most for three days. There were body weight reductions in males and females. At necropsy no abnormalities were detected. Only in the deceased female rat the gastro-intestinal tract was severely autolytic.  

In an acute dermal toxicity study conducted using a protocol comparable to OECD 402, and to GLP (WIL Research Laboratories, 2000) the LD50 for male rabbits was 6730 mg/kg bw, and for females was at least 8000 mg/kg bw. Dermal reactions included erythema, edema, necrosis, fissuring, desquamation and alopecia (signs of skin irritation at all doses in both sexes). Signs of toxicity included sluggishness, an unsteady gait, laboured breathing, forelimb paralysis (one male that died), hindlimb paresis (reversible weakness to temporary loss of ability to stand), nephrititis, slight wetness of the perinasal fur, head with swaying motion. Recovery of survivors was 2-14 days. There were no treatment-related microscopic findings.  In an acute inhalation study conducted using a protocol that was similar to OECD 403, and to GLP (BRRC, 1992) the LC50 was at least 22 ppm, approximately 0.25 mg/l (the highest dose tested) in rats. The were no deaths and no significant clinical effects, effects on bodyweight or gross necropsy findings.

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:
26.09.1991 to 16.10.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: EEC 84/449/EEC
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
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: 8 weeks; Females: 9 weeks.
- Weight at study initiation: Males: 151-167 g; Females: 135-147 g.
- Fasting period before study: 16 hours
- Housing: Macrolon cages, Type II
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-22.5
- Humidity (%): 40-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02.10.1991 To:16.10.1991
Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 21.5 ml/kg
Doses:
5110 mg/kg bw
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: Animals were continuously observed for the first 4 to 6 hours after administration and then once daily. Mortality was checked twice daily. Body weights were recorded before the first dose and then on days 7 and 14, or after death.
- Necropsy of survivors performed: yes, a gross necropsy was performed on all animals. Macroscopic examinations included external appearance, body orifices, body cavities (thoracic and abdominal), and their contents.
Statistics:
None. LD50s were estimated.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 5 110 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The study report states that the LD50 for females is approximately 5110 mg/kg bw, however, only 1/5 females died. Therefore the author of this study record has concluded that the overall LD50 is at least 5110 mg/kg bw for males and females.
Mortality:
One female animal died on day 7 after administration.
Clinical signs:
Signs of intoxication were slight to moderate hypokinesia, diarrhoea and piloerection in male and female rats. In addition, individual female animals showed coordination disturbances, stilted gait, red encrusted snout, strenuous respiration, sunken sides and vocalisation on handling. In general symptoms were observed on days two to three. In one female, first symptoms appeared 160 minutes after administration. In individual females signs of toxicity lasted for 14 days or until death. In male animals symptoms lasted at most for three days.
Body weight:
Body weight reductions in males and females.
Gross pathology:
At necropsy no abnormalities were detected. Only in the deceased female rat the gastro-intestinal tract was severely autolytic.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study conducted to the now deleted OECD 401 and to GLP (reliability score 1) the LD50 for triethoxy(octyl)silane was at least 5110 mg/kg bw in rats. Signs of intoxication were slight to moderate hypokinesia, diarrhoea and piloerection in male and female rats. In addition, individual female animals showed coordination disturbances, stilted gait, red encrusted snout, strenuous respiration, sunken sides and vocalisation on handling. In general symptoms were observed on days two to three. In one female, first symptoms appeared 160 minutes after administration. In individual females signs of toxicity lasted for 14 days or until death. In male animals symptoms lasted at most for three days. There were body weight reductions in males and females. At necropsy no abnormalities were detected. Only in the deceased female rat the gastro-intestinal tract was severely autolytic.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
5 110 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:
10.05.1996 to 28.07.2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Qualifier:
according to
Guideline:
EPA OTS 798.1150 (Acute inhalation toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., 9801 Shaver Road, Portage, MI 49081
- Age at study initiation: 'young'
- Weight at study initiation: 232-245 g
- Fasting period before study: No
- Housing: Individual suspended wire-mesh cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: minimum seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6-22.2
- Humidity (%): 32-72
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23.05.1996 To: 06.06.1996
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 500 l glass and stainless steel exposure chamber
- Method of holding animals in test chamber: Individual cages
- Source and rate of air: Flow rate was 0.025 ml/min
- Method of conditioning air: No data
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: No data

TEST ATMOSPHERE
- Brief description of analytical method used: The nominal exposure concentration was calculated as the ratio of the total amount of test substance used during the exposure divided by the total volume of air passed through the chamber during the exposure. Since the saturated vapour concentration was not known precisely, it was decided to measure the exposure atmosphere using a total hydrocarbon analyser (THCA), and then on the following day prepare gas bag calibration standards that bracketed the instrument response obtained during the exposure. The actual concentrations were then to be calculated from the resulting standard curve.
- Samples taken from breathing zone: No data
Analytical verification of test atmosphere concentrations:
yes
Remarks:
using a total hydrocarbon analyser
Duration of exposure:
4 h
Concentrations:
Estimated to be less than 22 ppm.
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 observed during the exposure and one hour after removal from the exposure chamber on day 0, and twice daily thereafter. Clinical observations were made upon removal from exposure on day 0 and once daily thereafter. Body weights were obtained immediately prior to exposure on day 0 and on days 3, 7 and 14.
- Necropsy of survivors performed: yes, all animals underwent a gross necropsy. The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.
Statistics:
None required.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 22 ppm
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no deaths.
Clinical signs:
other: During the exposure, the only clinical finding was hyperactivity noted in one female. Following exposure there were no clinical findings.
Body weight:
There were no effects on body weight.
Gross pathology:
At necropsy, only two abnormalities were noted. One female exhibited dark red lungs and one male exhibited a white area on the spleen. All other animals were considered normal.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute inhalation study conducted using a protocol that was similar to OECD 403, and to GLP (reliability score 1) the LC50 was at least 22 ppm (the highest dose tested) in rats. The were no deaths and no significant clinical effects, effects on bodyweight or gross necropsy findings.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
250 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01.08.1991 to 10.10.1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
other: TSCA
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton research Products, Inc., Denver, PA.
- Age at study initiation: 12 to 18 weeks
- Weight at study initiation: 2.1 to 3.2 kg
- Fasting period before study: No
- Housing: Individually in cages with wire floors
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-22.2
- Humidity (%): 33-60%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 01.08.1991 to 10.10.1991
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal trunk
- % coverage: Not stated - "as large an area as possible" was treated.
- Type of wrap if used: A double layer of gauze sheeting was wrapped around the trunk and secured with adhesive tape. Polyethylene sheeting was then wrapped around the trunk over the gauze. The sheeting was protected with bandaging tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): volume varied according to the weight of the rabbits.
Duration of exposure:
24 hours
Doses:
2, 4 and 8 g/kg bw
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: Animals were observed frequently for signs of toxicity on the first day of the test, and twice daily thereafter. Weights were recorded on the day of dosing and at 7 and 14 days after dosing and death.
- Necropsy of survivors performed: yes, after 14 days, all survivors were sacrificed. Microscopic examinations were performed on selected tissues from several rabbits.
Statistics:
The LD50 was calculated by the Moving Average Method.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
6 730 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 8 000 mg/kg bw
Based on:
test mat.
Mortality:
One of the female rabbits died following a dose of 8 g/kg bw, but there were no deaths following 4 and 2 g/kg bw. Three, one and no male animals died at 8, 4 and 2 g/kg bw. Deaths occurred on days three to six.
Clinical signs:
Dermal reactions included erythema, edema, necrosis, fissuring, desquamation and alopecia (signs of skin irritation at all doses in both sexes). Signs of toxicity included sluggishness, an unsteady gait, laboured breathing, forelimb paralysis (one male that died), hindlimb paresis (reversible weakness to temporary loss of ability to stand), nephrititis, slight wetness of the perinasal fur, head with swaying motion. Recovery of survivors was 2-14 days.
Body weight:
Weight loss was observed, so animals with emaciation.
Gross pathology:
Necropsy of the animals that died revealed hemorrhaged intestines (one animal) and a small amount of blood in the urine of one. In survivors there were instances of dark/bright red lungs, intestines of one animal were partially filled with gas, an enlarged spleen and a raised tan nodule on one kidney.
Other findings:
Selected tissues from six males and six females were examined microscopically. Lesions observed included interstitial nephritis and calculi in the urinary bladder. These findings were considered to be incidental and not related to the treatment. There were no lesions apparent in the examined spinal cords or sciatic nerves of any animal.

Table 1 Summary of acute dermal study results

Dose (g/kg bw)  Dead/dosed  Mean weight (g ± SD)         Signs of toxicity
     0 days  7 days  14 days  
 8.0 (males)  3/5  2364 ± 116  2228 ± 97  2448 ± 86  Sluggishness in 1 at day 1, emaciation of 1 at death. Weight loss evident in survivors at 7 days with recovery by 14 days.
 4.0 (males)  1/5  2534± 153  2360 ± 89  2496 ± 164 Sluggishness in 1, unsteady gait in 2 at day 1; laboured breathing and forelimb paralysis in 1 that died at 1 day; hindlimb paresis in 3 at 2 days, emaciation of 1 at death. Partial recovery of 2 from paresis at day 7. Complete recovery of 3 at 2 to 14 days.  
 2.0 (males)  0/5  2604± 202  2444± 166  2651± 160 Iritis in 1 at day 1. Recovery at 2 days. Emaciation of 1 at 6 days, paresis (weakness) in all limbs of 1 at 7 days. Complete recovery at 14 days.  
 8.0 (females)  1/5  2778± 63  2368± 254  2551± 277  Sluggishness in 2, unsteady gait in 1, laboured breathing in 1, slight wetness of perinasal fur of 1 at day 1; paresis (difficulty in standing) in 2 survivors at 1 or 7 days; emaciation of 3 at death or 7 days. Death of 1 at 4 days. All survivors recovered at 7 to 14 days.
 4.0 (females)  0/5  2415± 151  2342± 180  2533± 192  Sluggishness and slight swaying motion of head in 1 at day 1. Recovery at 14 days.
 2.0 (females)  0/5  2277± 85 2323± 69   2575± 110  None noted.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study conducted using a protocol comparable to OECD 402, and to GLP (reliability score 1) the LD50 for male rabbits was 6730 mg/kg bw, and for females was at least 8000 mg/kg bw. Dermal reactions included erythema, oedema, necrosis, fissuring, desquamation and alopecia (signs of skin irritation at all doses in both sexes). Signs of toxicity included sluggishness, an unsteady gait, laboured breathing, forelimb paralysis (one male that died), hindlimb paresis (reversible weakness to temporary loss of ability to stand), nephrititis, slight wetness of the perinasal fur, head with swaying motion. Recovery of survivors was 2-14 days. There were no treatment-related microscopic findings.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
6 730 mg/kg bw

Additional information

There are two studies conducted in 1992 with reliability scores of 1. Both show that the acute oral toxicity of triethoxy(octyl)silane is low and does not require classification. For the inhalation route the most recent study was selected as the key study. The supporting study also showed that the highest attainable concentration was of low acute toxicity. The dermal study was the only acute dermal study available.


Justification for classification or non-classification

No classification is required for triethoxy(octyl)silane for acute toxicity (lethality) following a single exposure according to Regulation (EC) No 1272/2008.

Following oral and dermal exposures there were signs of narcosis (sluggishness, unsteady gait, coordination disturbances). 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.