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Administrative data

Description of key information

In the key acute oral toxicity study, available from an IUCLID summary and claimed to be conducted using a protocol comparable to the now deleted OECD Test Guidelines 401, but predating GLP (Mellon Institute, 1956), the LD50 for 3-(triethoxysilyl)propiononitrile was 5600 mg/kg bw in male Wistar rats.

In the key acute dermal toxicity study, available from an IUCLID summary and claimed to be conducted using a protocol comparable to the OECD Test Guidelines 402, but predating GLP (Mellon Institute, 1956), the LD50 for 3-(triethoxysilyl)propiononitrile was 5753 mg/kg bw in male New Zealand White rabbits.

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:
1956
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)
GLP compliance:
no
Test type:
other: LD50
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Age at study initiation: 5 to 6 weeks

- Weight at study initiation: 90-120 grams

- Fasting period before study: not fasted
Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
T52-003: 10% dilution in corn oil
Details on oral exposure:
VEHICLE

- Concentration in vehicle: as a 10% dilution


MAXIMUM DOSE VOLUME APPLIED: ca. 5 for 7.95 g/kg dose and ca. 8ml for 3.98 g/kg dose


Doses:
7950 and 3980 mg/kg bw
No. of animals per sex per dose:
3.98 g/kg bw: 5 rats
7.95 g/kg bw: 4 rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: no data available

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: no data available
Statistics:
Thompson's method of calculating the median-effective dose (LD50) was applied to the 14-day mortality data.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
5 600 mg/kg bw
Based on:
test mat.
Remarks:
median-effect dose, calculated from the 14-day mortality data
Remarks on result:
other: No range is given because there was 100% mortality at 7.95 g/kg bw and 100% survival at 3.98 g/kg bw
Mortality:
All animals administered the higher dose died. No mortalities were seen at the lower dose.
Clinical signs:
other: 3.98 g/kg bw: no data available At 7.95 g/kg bw: Violent convulsions followed the administration of the doses and death ensued in a few hours.
Gross pathology:
3.98 g/kg bw: no data available
At 7.95 g/kg bw: Lungs were hemorrhaged, livers and kidneys mottled and adrenals slightly congested at autopsy.
Other findings:
No data available.

Table 1: Number of animals dead and time range within which mortality occured

 Dose
(mg/kg
bw)

Mortality (# dead/total)

Time range of deaths (day)

Male

Female

Combined

3.98

 0/5

 -

 0/5

 -

7.95

 4/4

 4/4

 

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study available from an IUCLID summary, claimed to be conducted using a protocol comparable to the now deleted OECD Test Guidelines 401, but predating GLP, the LD50 was determined to be 5600 mg/kg bw/day in male Wistar rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 600 mg/kg bw

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:
1956
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)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Age at study initiation: 3 to 5 months

- Weight at study initiation: mean 2.5 kg
Type of coverage:
not specified
Vehicle:
other: undiluted
Details on dermal exposure:
TEST SITE

- Area of exposure: the trunk

- Type of wrap if used: "Vinylite" sheeting was used to retain the dose in contact with the clipped skin of the trunk 


No other details on dermal exposure available.
Duration of exposure:
24 hours
Doses:
5.0 and 10.0 ml/kg bw
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: No details available.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: No details available.
Statistics:
Thompson's method of calculating the LD50 was used.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
5 753 mg/kg bw
Based on:
test mat.
Mortality:
All animals died within one day at the 10.0 ml/kg bw dose level, one animal died on the first day at the 5.0 ml/kg bw dose level.
Clinical signs:
other: Skin erythema with slight necrosis in several cases resulted from these covered applications.
Gross pathology:
Dosage: 10.0 ml/kg bw: The lungs were slightly congested, the kidneys pale and pitted, and livers mottled.
Dosage: 5.0 ml/kg bw: None reported.
Other findings:
No other findings reported/available.

Table 1: Number of animals dead and time range within which mortality occurred

 Dose
(mg/kg
bw)

Mortality (# dead/total)

Time range of deaths (day)

Male

Female

Combined

5.0

 1/3

 1/3

10.0

 3/3

 -

 3/3

 1

 

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study available from an IUCLID summary, claimed to be conducted using a protocol comparable to the OECD Test Guideline 402 , but predating GLP, the LD50 was determined to be value of 5753 mg/kg bw/day in male New Zealand White rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 753 mg/kg bw

Additional information

In the key acute oral toxicity study available from an IUCLID summary and claimed to be conducted using a protocol comparable to the now deleted OECD Test Guidelines 401, but predating GLP (Mellon Institute, 1956), the LD50 for 3(triethoxysilyl)propiononitrile was 5600 mg/kg bw in male Wistar rats. At the upper dose level of 7950 mg/kg, clinical signs included violent convulsions prior to death, and haemorrhagic lungs, mottled livers and kidneys and slightly congested adrenals were seen at necropsy. There were no deaths, clinical signs or necropsy findings at the lower dose level of 3980 mg/kg bw.

In the key acute dermal toxicity study available from an IUCLID summary and claimed to be conducted using a protocol comparable to the OECD Test Guidelines 402 , but predating GLP (Mellon Institute, 1956), the LD50 for 3(triethoxysilyl)propiononitrile was 5753 mg/kg bw in male New Zealand White rabbits. At the high dose of 9669 mg/kg bw, slightly congested lungs, pale and pitted kidneys and mottled livers were seen at necropsy. No clinical signs were reported, although there were signs of local irritation and necrosis.

The LD50 values in both key studies were well in excess of the upper limit for acute toxicity testing according to current EU guidelines of 2000 mg/kg bw.

The acute inhalation test did not meet current guideline requirements but adds weight of evidence to the low acute toxicity of the substance. It has therefore been assigned reliability 4 and used as supporting information only.

Justification for classification or non-classification

Based on the available measured LD50 values, 3-(triethoxysilyl)propiononitrile does not meet the criteria for classification for acute toxicity according to Regulation (EC) No 1272/2008.