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Toxicological information

Acute Toxicity: dermal

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Administrative data

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

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-trimethoxysilylpropane-1-thiol
EC Number:
224-588-5
EC Name:
3-trimethoxysilylpropane-1-thiol
Cas Number:
4420-74-0
Molecular formula:
C6H16O3SSi
IUPAC Name:
3-trimethoxysilylpropane-1-thiol
Details on test material:
- Name of test material (as cited in study report): Silane Y9616 (gamma-mercaptopropyltrimethoxysilane)
- Substance type: Organosilane
- Physical state: Liquid
- Stability under test conditions:
- Storage condition of test material: No data

Test animals

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

Administration / exposure

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

Results and discussion

Effect levelsopen allclose all
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:
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.
Body weight:
No effect on body weight reported.
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.

Applicant's summary and conclusion

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.