Registration Dossier

Administrative data

Description of key information

In an acute oral gavage study (Bushy Run Research Center, 1982), not conducted to GLP and following a protocol that was similar to the now deleted OECD 401 test guideline (reliability score 2), the oral LD50 for 3-(trimethoxysilyl)propiononitrile in rats was 9.85 ml/kg bw for males and 11.3 ml/kg bw for females (9555 mg/kg bw and 10961 mg/kg bw, respectively, based on relative density of 0.97 g/cm3). Signs of toxicity included sluggishness, unsteady gait and prostration. Necropsy revealed gas, liquid or solid filled stomachs and intestines, enlarged kidneys and dark lungs.  

In an acute dermal toxicity study (Bushy Run Research Center, 1982), conducted using a protocol similar to OECD 402, but not to GLP (reliability score 2), the dermal LD50 for 3-(trimethoxysilyl)propiononitrile was greater than 16 ml/kg bw (15520 mg/kg bw, respectively, based on relative density of 0.97 g/cm³) in rabbits.

There are no reliable inhalation data.  

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
some study details missing, including TS purity.
Principles of method if other than guideline:
To investigate the potential toxicity of a single dose of the test substance.
GLP compliance:
no
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: No data
- Age at study initiation: No data
- Weight at study initiation: 200-300 g
- Fasting period before study: Yes, overnight
- Housing: No data
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data

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

IN-LIFE DATES: No data
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 16 ml/kg
Doses:
4, 8 and 16 ml/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: Daily, and weighing on days 0, 7 and 14.
- Necropsy of survivors performed: yes, gross examination.
Statistics:
LD50 calculated using moving average method.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
9.85 mL/kg bw
Based on:
test mat.
95% CL:
>= 7.15 - <= 13.6
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
11.3 mL/kg bw
Based on:
test mat.
95% CL:
>= 6.43 - <= 19.9
Mortality:
No deaths occurred in the lowest dose group. One male and one female died in the mid dose group (by day 5), and at the highest dose only one female survived the 14 day observation period (all animals died by six).
Clinical signs:
Signs of toxicity included sluggishness, unsteady gait and prostration.
Body weight:
No effects.
Gross pathology:
Necropsy revealed gas, liquid or solid filled stomachs and intestines, enlarged kidneys and dark lungs.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral gavage study, not conducted to GLP (reliability score 2), the oral LD50 for 3-(trimethoxysilyl)propionitrile in rats was 9.85 ml/kg bw for males and 11.3 ml/kg bw for females (9555 mg/kg bw and 10961 mg/kg bw, respectively, based on relative density of 0.97 g/cm3). Signs of toxicity included sluggishness, unsteady gait and prostration. Necropsy revealed gas, liquid or solid filled stomachs and intestines, enlarged kidneys and dark lungs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
9 555 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Lack of details on test substance and environmental conditions of animals. Only four animals per dose used (guideline requires 5).
GLP compliance:
no
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: No data
- Age at study initiation: No data
- Weight at study initiation: 2-3 kg
- Fasting period before study: No
- Housing: No data
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data

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

IN-LIFE DATES: No data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Trunk
- % coverage: No data
- Type of wrap if used: Impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 16 and 8 ml/kg
- Constant volume or concentration used: yes, undiluted
Duration of exposure:
24 Hours
Doses:
Males: 16 ml/kg bw.
Females: 16 and 8 ml/kg bw.
No. of animals per sex per dose:
Four
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: after one hour, 7 days and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: body weights (0, 7 and 14 days) and clinical signs.
Statistics:
The LD50 was calculated using the moving averages method and are based on a 14 -day observation period.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 mL/kg bw
Based on:
test mat.
Mortality:
The maximum dermal application of the test substance (16 ml/kg bw) lead to one death in male rabbits and no deaths in female rabbits. Therefore, an LD50 could not be determined.
Clinical signs:
None
Body weight:
No effects.
Gross pathology:
At necropsy there were signs of lung infection in the males that died before the end of the 14 day observation period: lung and upper thoracic cavity fluid-filled and covered with yellow puss. Some males and females were found to have red patches in the trachea and lungs.
Other findings:
Capillary injection, erythema, oedema were observed one day after exposure in male and female animals. By 7 and 14 days scabs and desquamation were observed in females only.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study conducted using a protocol similar to OECD 402, but not to GLP (reliability score 2), the dermal LD50 for 3-(trimethoxysilyl)propiononitrile was greater than 16 ml/kg bw (15520 mg/kg bw, based on relative density of 0.97 g/cm3) in rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
15 520 mg/kg bw

Additional information

The key data described are the only data available for the registration substance. Supporting information is included for the analogue substance 3-(triethoxysilyl)propiononitrile (CAS 919-31-3).


Justification for classification or non-classification

Based on the available acute toxicity data, 3-(trimethoxysilyl)propiononitrile is not classified for acute toxicity (lethality) following a single exposure according to EU Regulation (EC) No 1272/2008.