Tris(2-methoxyethoxy)vinylsilane

Endpoint summary

Description of key information

In the key acute oral toxicity study (WIL Research Laboratories, 1999a), conducted according to OECD Test Guideline 401 and in compliance with GLP, the LD₅₀ for rats was determined to be =2000 mg/kg bw. 

In the key acute dermal toxicity study (WIL Research Laboratories, 1999b), conducted according to OECD Test Guideline 402 and in compliance with GLP, the LD50 for rats was determined to be =2000 mg/kg bw. There were no clinical signs or abnormalities at necropsy although, local desquamation was observed.

In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and dermal routes are available.

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:

3 March 1999 - 21 June 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles river Laboratories, Raleigh, NC
- Age at study initiation: 10-11 weeks (males), 11-12 weeks (females)
- Weight at study initiation: 274-353 grams (males), 212-262 grams (females) at initiation of dosing
- Housing: individually suspended wire-mesh cages.
- Diet: PMI Nutrition International, Inc. Certified Rodent LabDiet 5002, ad libitum
- Water: reverse osmosis treated municipal water, ad libitum
- Acclimation period: minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.1-22.3
- Humidity (%): 45-56
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No data available.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The test animals were observed for overt signs of toxicity at 1, 3, and 4 hours, and once daily thereafter for 14 days. Animals were observed twice daily for mortality. Body weights were recorded on Days 0, 7, and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Examination of the cranial, thoracic and abdominal cavities was carried out after sacrificing the animals.

Statistics:

No data available.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One male and one female died during the first week of dosing.

Clinical signs:

other: A majority of the rats were noted with various discoloured areas due to discharges/excretions. Other findings in approximately one-third of the animals included abnormal excretion, hypoactivity and tremors.

Gross pathology:

Gastrointestinal abnormalities were noted for one animal that died.

Other findings:

No other findings reported.

Based on these results, the acute oral LD50 of A-172 was determined to be greater than 2000 mg/kg, indicating a very low order of toxicity in the rat by this route.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Not classified according to Regulation (EC) No. 1272/2008.

Conclusions:

In an acute oral toxicity study, conducted according to an appropriate test protocol and in compliance with GLP, an LD50 value of >2000 mg/kg bw for rats was determined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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:

3 March 1999 - 20 May 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Raleigh, NC
- Age at study initiation: 9-10 weeks (males), 10-11 weeks (females) old at initiation of dosing
- Weight at study initiation: 295-327 grams (males), 218 - 262 grams (females)
- Housing: individual suspended wire mesh cages
- Diet: PMI Nutrition International, Inc. Certified Rodent LabDiet 5002, ad libitum
- Water: reverse osmosis-treated municipal water, ad libitum
- Acclimation period: minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.05-22.3 °C
- Humidity (%): 45-56.2 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped dorsal skin
- % coverage: 18-23 %
- Type of wrap if used: the application area was overwrapped with gauze binders that were secured with nonirritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing: the application sites were wiped with disposable paper towels moistened with tepid water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test article was dosed undiluted based on its specific gravity. The dose volume was determined by dividing the dose level (2000 mg/kg) by the specific gravity (1.05 g/mL). Individual doses were calculated based on body weights taken just prior to dosing and the dose volume of 1.90 mL/kg.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for overt signs of toxicity at 1, 3, and 4 hours, and once daily thereafter, for a total of 14 days. Animals were observed twice daily for mortality. Body weights were recorded on days 0, 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Examination of the cranial, thoracic and abdominal cavities was carried out following termination.
  

Statistics:

No statistical analysis presented.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: Desquamation was noted sporadically during the study for five rats.

Gross pathology:

There were no remarkable gross necropsy findings.

Other findings:

There were no other test article related dermal findings.

The acute percutaneous LD₅₀ of tris(2-methoxyethoxy) vinylsilane was determined to be  >2000 mg/kg, indicating a very low order of toxicity in the rat by this route.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study, conducted according to OECD 402 and in compliance with GLP, an LD50 value of >2000 mg/kg bw was determined for rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

In the key acute oral toxicity study, conducted according to OECD Test Guideline 401 and in compliance with GLP, the LD50 for rats was determined to be =2000 mg/kg bw. The majority of the rats were noted to have various discoloured areas due to discharge/excretions. Other findings in approximately one-third of the animals included abnormal excretion, hypoactivity and tremors. One male and one female died at the 2000 mg/kg bw dose level. Gastrointestinal abnormalities were detected at necropsy in one of the animals that died (WIL Research Laboratories, 1999a).

In a supporting acute oral toxicity study, conducted according to OECD Test Guideline 401 but pre-GLP, an LD₅₀ of 2.3 ml/kg bw/day, equivalent to 2346 mg/kg bw/day was determined (Consultox Laboratories, 1976).

In a supporting acute oral toxicity study, conducted in a similar manner to OECD Test Guideline 401 but pre-GLP, determined an LD₅₀ for male rats to be 2.96 g/kg which is equivalent to 2960 mg/kg bw/day (Mellon Institute, 1954).

In a supporting acute oral toxicity study, conducted according to OECD Test Guideline 401 but pre-GLP, an LD₅₀ of 2750 mg/kg bw/day was concluded (Laboratoires Recherches de la Societe, 1972).

In the key acute dermal toxicity study, conducted according to OECD Test Guideline 402 and in compliance with GLP, 5 male and 5 female rats were exposed to 2000 mg/kg bw/day of tris(2-methoxyethoxy)vinylsilane under semi-occlusive conditions. After 24 hours exposure, the application sites were wiped with disposable paper towels moistened with tepid water. The observation period ranged over 14 days and observations including clinical signs, body weight, organ weights, histopathology and examination of the cranial, thoracic and abdominal cavities following termination were noted. The degree of erythema, eschar formation and oedema at the application site was assessed 30-60 minutes after exposure and at daily intervals thereafter. An LD50 of =2000 mg/kg bw/day was determined (WIL Research Laboratories, 1999b).

In a supporting acute dermal toxicity study in rabbits, conducted in a similar manner to OECD Test Guideline 402 but pre-GLP, an LD₅₀ of 1.5 mL/kg bw/day (equivalent to approximately 1545 mg/kg based on a density of 1.02 g/cm³) was concluded (Mellon Institute, 1954).

Justification for classification or non-classification

Based on the available data, tris(2-methoxyethoxy)vinylsilane does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.