3-(trimethoxysilyl)propiononitrile

Endpoint summary

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

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 or test system 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:

other: Signs of toxicity included sluggishness, unsteady gait and prostration.

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

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 or test system 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:

other: None

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.