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Description of key information

The key study for acute oral toxicity (Eurofins, 2018) was conducted according to OECD 423 and in compliance with GLP. The acute oral LD50 was identified to be 500 mg/kg bw for female rats.

The key study for acute dermal toxicity (BRRC 1990) was conducted according to a test protocol that is comparable to the appropriate OECD Test Guideline 402, but not in compliance with GLP. The acute dermal LD50 was identified to be 2497 mg/kg bw for males and 2172 mg/kg bw for females.

The key acute inhalation toxicity study (BRRC 1990) was conducted according to a protocol similar to OECD Test Guideline 403, not in compliance with GLP. 3-Trimethoxysilylpropane-1-thiol did not cause any deaths in Sprague-Dawley rats following a six hour exposure to saturated vapour.  

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:
26th of July 2018 to 28th of August 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted 17 December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Commission Regulation (EC) No. 440/2008, L 142
Version / remarks:
Annex Part B, Method B.1, tris 30 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
EPA 712-C-02-190, December 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 152-165 g
- Fasting period before study: 16-19 hours
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Diet: ad libitium of Altromin 1324 maintenance diet for rats and mice
- Water: ad libitum of free access to tap water, sulphur acidified to a pH value of approximately 2.8.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 July 2018 To: 28 August 2018
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
300 mg/kg bw and 2000 mg/kg bw.
No. of animals per sex per dose:
3 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighting on day 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, pathology
Statistics:
With a few exceptions, data were captured using the validated departmental computerised system E-WorkBook (version 10.1.2, ID Business Solutions Ltd.).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut off
Mortality:
At 2000 mg/kg bw, mortality occurred in two rats on day two and one rat was euthanised for ethical reasons. At 300 mg/kg bw, no mortality was observed.
Clinical signs:
other: At 2000 mg/kg bw, the test material caused clinical signs including reduced spontaneous activity, ataxia, moving of the bedding, sunken flanks, prone position, hunched posture, hypothermia, tremor and slow movements. At 300 mg/kg bw, the test material ca
Gross pathology:
At 2000 mg/kg bw, gazeous distension and dilated blood vessels were observed at necropsy. At 300 mg/kg bw, no specific gross pathological changes were recorded.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study with 3-trimethoxysilylpropane-1-thiol, conducted according to OECD TG 423 and in compliance with GLP, the concluded LD50 value was 500 mg/kg bw.
Executive summary:

In an acute oral toxicity study with 3-trimethoxysilylpropane-1-thiol, conducted according to OECD TG 423 and in compliance with GLP, the concluded LD50 value for female rats was 500 mg/kg bw based on severe signs of toxicity and mortality at 2000 mg/kg bw, and slight signs of toxicity but no mortality at 300 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw
Quality of whole database:
The key study for acute oral toxicity was conducted according to OECD test guideline and in compliance with GLP.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not stated
- Age at study initiation: Not stated
- Weight at study initiation: 200 - 300 g
- Fasting period before study: No
- Housing: Not stated
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not stated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated
- Humidity (%): Not stated
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): Not stated

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: no data
Details on inhalation exposure:
The vapour was produced by enclosing approximately 100 g of the test substance in a sealed 100 to 151 L animal chamber for approximately 18 hours (static conditions). A mixing fan periodically aggitated the chamber atmosphere. Oxygen was added as required to maintain a chamber oxygen content of approximately 20%. If deaths occurred, exposure times were varied to determine an LT50.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 6 h
Concentrations:
Saturated vapour
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: Weights: day 0 (prior to exposure), day 7 and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
None
Sex:
male/female
Effect level:
other: saturated vapour
Exp. duration:
6 h
Remarks on result:
other: No deaths
Mortality:
No deaths occurred
Clinical signs:
other: Fur slightly moist, periodic rubbing of head, eyes and nose during exposure. Recovery occurred within one hour of the end of exposure.
Body weight:
No effects on body weight gain
Gross pathology:
No findings
Other findings:
No other findings reported
Interpretation of results:
study cannot be used for classification
Conclusions:
In a good quality (reliability score 2) acute inhalation toxicity study, not conducted to GLP, 3-trimethoxysilylpropane-1-thiol did not cause any deaths in Sprague-Dawley rats following a six hour exposure to a saturated vapour.
Executive summary:

In an acute inhalation study comparable to OECD test guideline 403, but not conducted to GLP, Sprague-Dawley rats were exposure to a saturated vapour of 3-trimethoxysilylpropane-1-thiol for six hours. They were then observed for 14 days. No deaths occurred and there was no effect on body weight gain. Fur slightly moist, periodic rubbing of head, eyes and nose during exposure. Recovery occurred within one hour of the end of exposure. There were no abnormal findings during the gross pathological examinations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not stated
- Age at study initiation: Not stated
- Weight at study initiation: 2-3 kg
- Fasting period before study: Not stated
- Housing: Not stated
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not stated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated
- Humidity (%): Not stated
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): Not stated

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not stated
- % coverage: Not stated
- Type of wrap if used: Occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: when dressings removed.


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 16 ml/kg bw was maximum
- Concentration (if solution): undiluted test substance used




Duration of exposure:
24 hours
Doses:
1.0, 2.0, and 4.0 ml/kg
No. of animals per sex per dose:
Five
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: one hour, seven days and 14 days. Body weights: before dosing, seven days and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross pathological examination
Statistics:
Not stated
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 2.46 mL/kg bw
95% CL:
>= 1.79 - <= 3.39
Remarks on result:
other: 2.46 ml/kg x 1.015 = 2497 mg/kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2.14 mL/kg bw
95% CL:
>= 1.45 - <= 3.17
Remarks on result:
other: 2.14 ml/kg x 1.015 = 2172 mg/kg bw
Mortality:
All male and female animals given 4.0 ml/kg bw died within one day of dosing. One male animal died at 2.0 ml/kg bw within one day of dosing. Two females died (Day 2 and 6) at 2.0 ml/kg bw. No animals died at 1.0 ml/kg bw.
Clinical signs:
other: A red liquid was apparent around the anus and/or the paperboard beneath the cages of several animals. Other signs of toxicity included sluggishness (two animals), unsteady gait (one animal), spasmodic movement (one animal), diarrhoea (one animal) and red
Gross pathology:
Necropsy of animals that died revealed red lungs, trachea filled with blood (two animals), the stomach of one animal had a red focal area, dark red kidneys, kidneys filled with blood (one animal) or a yellow to green gelatinous material, a dark red bladder (in one), blood in the urine of one animal and dark red enlarged lymph nodes. There were also instances of vascularisation and haemorrhages on the skin.
Gross pathological examination of survivors revealed mottled red lungs (two with dark red foci), tracheas filled with blood and excoriation of the treated skin.
Other findings:
- Organ weights: not measured.
- Histopathology of potential target organs: The kidneys and bladders of two male and two female rabbits from all dose groups were subjected to detailed histological examination. At high doses of 2.0 and 4.0 ml/kg bw kidneys lesions included epithelial necrosis of the renal pelvis, tubular epithelial cell degeneration and proteinosis. There were no kidney lesions at 1.0 ml/kg bw, and no significant urinary bladder lesions at any dose.
- Other observations: Local cutaneous effects included erythema, oedema, necrosis, desquamation, fissuring, ulceration, alopecia and scabs.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
In a good quality (reliability score 2) acute dermal toxicity study, not conducted to GLP, the dermal LD50 for 3-trimethoxysilylpropane-1-thiol was 2.46 ml/kg bw for males and 2.14 ml/kg bw for females New Zealand white rabbits.
Executive summary:

In a study comparable to OECD test guideline 402, but not conducted to GLP, 3-trimethoxysilylpropane-1-thiol was applied to the shaved backs of five male and five female New Zealand white rabbits, under an occlusive dressing for 24 hours. The skin was washed at the end of the exposure period. Doses were adjusted by altering the volumes of the undiluted test substance applied. The volumes used were 4.0, 2.0 and 1.0 ml/kg bw. All male and female animals given 4.0 ml/kg bw died within one day of dosing. One male animal died at 2.0 ml/kg bw, within one day of dosing. Two females died (Day 2 and 6) at 2.0 ml/kg bw. No animals died at 1.0 ml/kg bw. Therefore the LD50 was 2.46 ml/kg bw for males, and 2.14 ml/kg bw for females. Local cutaneous effects included erythema, oedema, necrosis, desquamation, fissuring, ulceration, alopecia and scabs. A red liquid was apparent around the anus and/or the paperboard beneath the cages of several animals. Other signs of toxicity included sluggishness (two animals), unsteady gait (one animal), spasmodic movement (one animal), diarrhoea (one animal) and red discharge around nose and mouth. Affected animals recovered with two to three days. Necropsy of animals that died revealed red lungs, trachea filled with blood (two animals), the stomach of one animal had a red focal area, dark red kidneys, kidneys filled with blood (one animal) or a yellow to green gelatinous material, a dark red bladder (in one), blood in the urine of one animal and dark red enlarged lymph nodes. There were also instances of vascularisation and haemorrhages on the skin. Gross pathological examination of survivors revealed mottled red lungs (two with dark red foci), tracheas filled with blood and excoriation of the treated skin. The kidneys and bladders of two male and two female rabbits from all dose groups were subjected to detailed histological examination. At high doses of 2.0 and 4.0 ml/kg bw kidneys lesions included epithelial necrosis of the renal pelvis, tubular epithelial cell degeneration and proteinosis. There were no kidney lesions at 1.0 ml/kg bw, and no significant urinary bladder lesions at any dose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 172 mg/kg bw
Quality of whole database:
The key study for acute dermal toxicity was conducted according to a test protocol that is comparable to the appropriate OECD test guideline, but not in compliance with GLP.

Additional information

The key study for acute oral toxicity (Eurofins, 2018) reports a LD50 value of 500 mg/kg bw for females. The clinical signs included reduced spontaneous activity, ataxia, moving of bedding, sunken flanks, prone position, hunched posture, hypothermia, tremor and slow movements, reduced spontaneous activity and half eyelid closure. The animals that died revealed gaseous distension and dilated blood vessels. No specific gross pathological changes were recorded for survivors at a lower dosage. Supporting acute oral toxicity studies were also available, which did not meet current guideline requirements or were conducted according to a similar test protocol and support the conclusion of the key study (DCC, 1969, DCC 1963, Consultox, 1976; BRRC, 1990). The selected key study was the most recent and gave the most conservative result, but all results would lead to the same classification conclusion of Acute Category 4 for oral toxicity.

An acute oral toxicity study is also available for the analogous substance from 3-(triethoxysilyl)propanethiol (CAS 14814-09-6) which reports an LD50value of 6.17 ml/kg (estimated to be equivalent to 6108 mg/kg bw) in rats in a reliable study conducted according to a protocol equivalent to the now-deleted OECD Test Guideline 401 (Carnegie-Mellon 1976). In the highest dose group (16 ml/kg) the animals were seen to be sluggish, deep breathing, with tremor-like muscular spasms and loss of coordination. The symptoms progressed to salivation and convulsions followed by the death of all three animals. Similar, but milder clinical signs were evident in the lower dosage groups. In victims, petechial haemorrhages or congestion was observed in the lungs. This was accompanied with mottled livers, slightly speckled and congested kidneys and distended and liquid or gas-filled intestines and stomachs. Nothing remarkable was seen in survivors.

The key study for acute dermal toxicity (BRRC 1990) reports LD50 values of 2497 mg/kg bw for males and 2172 mg/kg bw for females. The clinical signs included sluggishness, unsteady gait, spasmodic movement, diarrhoea and red discharge around nose, mouth and anus. Affected animals recovered with two to three days. Necropsy of animals that died revealed red lungs, trachea filled with blood, the stomach of one animal had a red focal area, dark red kidneys, kidneys filled with blood or a yellow to green gelatinous material, a dark red bladder, blood in the urine of one animal and dark red enlarged lymph nodes. There were also instances of vascularisation and haemorrhages on the skin. Gross pathological examination of survivors revealed mottled red lungs, tracheas filled with blood and excoriation of the treated skin.

Additional acute dermal toxicity studies were also available for the registration substance, which did not meet current guidelines, but these add supporting information for this endpoint and support the conclusion of the key study (DCC 1969, DCC 1963).

An acute dermal toxicity study is also available for the analogue substance 3-(triethoxysilyl)propanethiol (CAS 14814 -09 -6) which reports and LD50 value of 2.52 ml/kg (estimated to be equivalent to 2494 mg/kg bw) in rat in a reliable study conducted according to a protocol equivalent to OECD Test Guideline 402 (Carnegie-Mellon 1976). Erythema, ecchymosis, scabs and desquamation were evident at application site with no other reported clinical signs. In victims, livers were paled and mottled, spleens dark and kidneys congested. No remarkable findings were seen in survivors.

The key acute inhalation toxicity study (BRRC 1990) was conducted according to a protocol similar to OECD Test Guideline 403, not in compliance with GLP. 3-Trimethoxysilylpropane-1-thiol did not cause any deaths in Sprague-Dawley rats following a six hour exposure to a saturated vapour of the test substance. The observed clinical signs of toxicity included slightly moist fur, periodic rubbing of head, eyes and nose during exposure, which were not evident at 1 hour post-exposure. No effects on body weight gain were observed. No other findings were reported.

Another two supporting acute inhalation toxicity studies were available, which did not meet current guideline requirements, but add supporting information for the endpoint and support the conclusion of the first study (DCC 1969, DCC 1963).


Justification for classification or non-classification

3-(Trimethoxysilyl)propane-1-thiol is classified for acute oral toxicity (Acute Oral Category 4; H302 Harmful if swallowed) according to Regulation (EC) 1272/2008. However, no peak oral exposures are expected and thus no hazard identified.