3-(triethoxysilyl)propiononitrile

Endpoint summary

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	0

 

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	1
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.