Trimethoxyvinylsilane

Endpoint summary

Description of key information

In the key acute oral toxicity study, conducted according to OECD Test Guideline 401 but not in compliance with GLP, the concluded LD50 values for male and female rats were 7.34 ml/kg and 7.46 ml/kg (equivalent to 6899 and 7012 mg/kg bw based on relative density of 0.94 g/cm³), respectively (Bushy Run Research Centre, 1984a).

In the key acute inhalation toxicity study, conducted according to OECD Test Guideline 403 but not in compliance with GLP, an acute inhalation LC50 value of 2773 ppm (16.8 mg/L) was determined for rats (Bushy Run Research Centre, 1986).

In the key acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 but not in compliance with GLP, LD50 (rabbit) values of 3.36 ml/kg bw for females and 4 ml/kg bw for males (equivalent to 3158 and 3760 mg/kg bw, respectively, based on relative density of 0.94 g/cm³) were determined (Bushy Run Research Centre, 1984b).

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:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The GLP status of the study is uncertain.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Remarks:

Although a statement regarding GLP was not available with the study report, it is known that this laboratory conducted studies in compliance with GLP at this time.

Test type:

other: LD50

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Hilltop Wistar albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 200- 300g

Route of administration:

other: intubation

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: not reported

Doses:

16.0, 8.0, 4.0, 2.0 and 1.0 ml/kg bw in males; 16.0, 8.0, 4.0 and 2.0 ml/kg bw in females

No. of animals per sex per dose:

45

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Body weights were recorded on days 0, (before dosing), 7 and 14 (prior to termination).

- Necropsy of survivors performed: yes.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At necropsy, each animal was subjected to gross pathologic evaluation.

Statistics:

LD50 with 95% confidence limits; males 7.34 (4.61 to 11.7) ml/kg; females 7.46 (5.16 to 10.8) ml/kg. LD50 slopes; males 3.67, females 4.22.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 7.34 - ca. 7.46 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Equivalent to 6899 and 7012 mg/kg bw based on relative density of 0.94 g/cm3

Mortality:

Deaths occurred at 2.5 hours to 4 days.

Clinical signs:

other: Sluggishness, red to brown discharge (around nose, eyes and anus), lacrimation, piloerection, unkempt appearance, prostation, emaciation and unsteady gait were amongst the signs of toxicity observed. Survivors recovered at one to 5 days. With the exceptio

Gross pathology:

At necropsy, there were several instances of dark red kidney section among victims.

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

 

Dose (ml/kg)	Mortality (# dead/total)			Time range of deaths (days)
	Male	Female	Combined
16	5/5	5/5	10/10	0 and 1
8	3/5	3/5	6/10	1,2,3,4
4	0/5	0/5	0/10
2	1/5	0/5	1/10	3
1	0/5	0/5	0/10

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity study, conducted according to OECD Test Guideline 401 with uncertain GLP status, the concluded LD50 values for male and female rats were 7.34 ml/kg and 7.46 ml/kg (equivalent to 6899 and 7012 mg/kg bw based on relative density of 0.94 g/cm3), respectively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 899 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The restrictions being that there was no report of whether the study was in compliance with GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River Breeding Laboratories, Inc., Kingston, NY

- Age at study initiation: 53 -56 days

- Housing: Two or three animals per cage were housed in in 23.5x20x18cm high stainless steel wire mesh cages on carriers .

- Diet: Pelleted feed (Certified Rodent Chow 5002, Relaton Purina Co., St. Louis, MO) was available ad libitum except during the exposure.

- Water: ad libitum, except during the exposure.




ENVIRONMENTAL CONDITIONS

- Temperature (°F): 66-76

- Humidity (%): 31-52

- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: none

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: A piston pump (Fluid Metering Inc., Oyster Bay, NY)

- Exposure chamber volume: ca. 1330 litres

- Method of holding animals in test chamber: The animals were in wire mesh cages inside the test chamber.

- Source and rate of air: No information available

- Temperature, humidity, pressure in air chamber: The temperature and relative humidity in the animal housing rooms were recorded continuously with a seven day recording hygrothermograph (Cole Parmer Instruments, Chicago, IL). During the exposure the temperature was monitored with an airguide Humidity Indicator (Airguide Instrument Co., Chicago, IL).


TEST ATMOSPHERE

- Brief description of analytical method used: A Perkin-Elmer Model 3920B gas chromatograph equipped with a flame ionization detector was used to monitor the A-171 vapor concentrations in the chambres. A Spectra-Physics Series 4000 central processor, a data interface, and a Perkin-Elmer automatic gas sampling system (station and valve programmer units and a gas sampling valve) were used for the analyses.

- Samples taken from breathing zone: Yes

- The test material originated from a heated evaporator similar in design to that described by Carpenter et al., 1975

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1981, 2335, 2798, 3547, and 5372 ppm (analytical). (Target concentrations of 2000, 2400, 2750, 3500 and 5000 ppm)

No. of animals per sex per dose:

5/sex (50 total)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were weighed prior to exposure and on post-exposure days seven and fourteen.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The animals were sacrificed following methoxyflurane anesthesis. The rats were exsanguinated by severing the brachial blood vessels and a complete necropsy was performed. Any abnormal tissues were placed in a fixative and saved for possible future histologic examination.

Statistics:

The mean and standard deviations of the body weights, body weight changes and exposure concentrations were calculated. No statistical comparisons were made. The LC50 was determined by the moving averages method of Thompson's (1947) using the 3547, 2798 and 2335 ppm exposure groups.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2 773 ppm

Exp. duration:

4 h

Remarks on result:

other: equivalent to 16.8 mg/L

Mortality:

Mortalities occurred at the 5372, 3547 and 2798 ppm concentrations in both male and female animals (see table 1).

Clinical signs:

other: Clinical signs included perinasal, encrustation, unkempt fur, hypoactivity, blepharospasm, lacrimation, respiratory difficulties (mouth breathing, audible respiration, decreased respiration rate), ataxia, prostration, tremors, distended stomachs, a negati

Body weight:

Depressed mean body weight gains were observed for both sexes of the 1981 and 2335 ppm groups and males of the 2798 ppm group during the first week of the post exposure period, when compared to mean body weight gains observed during the second postexposure week.

Gross pathology:

Two males and four females of the 5372 exposure group had eye opacities with three males and five females also having gas-filled stomachs. There were no other gross lesions in any of the other exposure groups.

Other findings:

No other findings reported.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute inhalation toxicity study, conducted according to OECD Test Guideline 403 with uncertain GLP status, an acute inhalation LC50 value of 2773 ppm (equivalent to 16.8 mg/l) was determined for rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

16 800 mg/m³ air

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:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

It was not compliant with GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

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

- Weight at study initiation: 2-3kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE

- Area of exposure: clipped, intact skin of the trunk

REMOVAL OF TEST SUBSTANCE

- Washing (if done): After the contact period, excess fluid was removed.

Duration of exposure:

24 hours

Doses:

8.0, 4.0 and 2.0 ml/kg bw

No. of animals per sex per dose:

5/sex/dose, except only 3 females dosed at 8.0 ml/kg bw (due to insufficient amount of test article)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:  Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period. Body weights were recorded on day 0 (before application), 7 and 14 (prior to termination). 

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:  At necropsy, each animal was subjected to gross pathologic evaluation.

Statistics:

LD50's were calculated by the moving average method (Thompson, 1947) and are based on a 14-day observation period.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3.36 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 3158 based on relative density of 0.94 g/cm3

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 3760 mg/kg bw based on relative density of 0.94 g/cm3

Mortality:

Most deaths occurred at one to 5 days (one rabbit died at 8 days).   

Clinical signs:

other: FEMALES: 8 ml/kg bw : sluggishness, unsteady gait at 3 minutes; marked sluggishness at 15 minutes; prostration at 2 hours. 4 ml/kg bw: Sluggishness, unsteady gait, lacrimation at 17 minutes; unkempt appearance, brown perianal discharge at 1 day. Survivors

Gross pathology:

At necropsy, lungs appeared red and mottled in animals that died.  A few livers were mottled or had red or white foci in animals that died.  No remarkable findings were noted in survivors.  

Other findings:

- Other observations: Skin reaction included erythema, ecchymosis and desquamation. Discomfort, sluggishness, unsteady gait, and prostration were observed.  Survivors recovered at 2 to 3 days.

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

 

Dose (mg/kg bw)	Mortality (# dead/total)			Time range of deaths (days)
	Male	Female	Combined
8	4/5	3/3	7/8	1,2,3
4	2/5	3/5	5/10	3,4,5
2	2/5	1/5	3/10	3,8

 

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 without information about GLP compliance, an LD50 (rabbit) values of 3.36 ml/kg bw for females and 4 ml/kg bw for males (equivalent to 3158 and 3760 mg/kg bw, respectively, based on relative density of 0.94 g/cm3) were determined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 158 mg/kg bw

Additional information

In the acute oral toxicity study, conducted according to OECD Test Guideline 401 but not in compliance with GLP, the concluded LD50 values for male and female rats were 7.34 ml/kg and 7.46 ml/kg (equivalent to 6899 and 7012 mg/kg bw based on relative density of 0.94 g/cm³), respectively (Bushy Run Research Centre, 1984a). 5 male and 5 female rats were administered single oral gavage dose of undiluted trimethoxy(vinyl)silane at doses of 16.0, 8.0, 4.0, 2.0 and 1.0 ml/kg bw for males and 16.0, 8.0, 4.0 and 2.0  ml/kg bw for females. Following administration, the animals were observed for 14 days. Body weights and clinical signs were recorded on a regular basis. At the end of the study period, the animals were sacrificed and subject to macroscopic examination. All rats treated with 16 ml/kg bw and 3 male and 3 female rats treated with 8 ml/kg bw died. One male rat treated with 2 ml/kg bw also died. Deaths occurred at 2.5 hours to 4 days post-dosing. Clinical signs included sluggishness, red to brown discharge, lacrimation, piloerection, unkempt appearance, prostration, emaciation and unsteady gait. At necropsy, dark red kidney sections were observed in animals that died at 16 and 8 ml/kg bw. There were no gross necropsy findings in animals that survived to the end of the study.

Several supporting studies were also available for acute oral toxicity.

An acute oral toxicity study conducted in accordance with OECD Test Guideline 423 (acute toxic class method) and in compliance with GLP, determined the LD50 value to be between 300 and 2000 mg/kg bw (Hashima Laboratories, 2005). Based on weight of evidence from several other available acute oral toxicity studies which report LD50s well above the limit dose, the result of this study is considered not to be representative of the acute toxicity of the test material.

An LD50 value of 11.3 ml/kg bw (equivalent to 10961 mg/kg bw) was determined in a reliable study conducted according to OECD Test Guideline 401, but not in compliance (Mellon Institute, 1962).

The LD50 value of 8.2 ml/kg bw (equivalent to 7954 mg/kg bw) was determined in a reliable study conducted according to OECD Test Guideline 401, but not in compliance with GLP (Consultox Laboratories, 1976).

In addition, two reliability 4 sources were also available which are in line with the results of the reliable studies (Smyth et al., 1969, Dow Corning Corporation, 1973).

In the acute inhalation toxicity study, conducted according to OECD Test Guideline 403 but not in compliance with GLP, an acute inhalation LC50 value of 2773 ppm (16.8 mg/L) was determined for rats (Bushy Run Research Centre, 1986). In the study, 5 male and 5 female rats per group were exposed to the vapours of the undiluted test material, trimethoxy(vinyl)silane, at concentrations of 1981, 2335, 2798, 3547, and 5372 ppm via single whole body inhalation for 4 hours. Following exposure, the animals were observed for 14 days. Body weights and clinical signs were recorded on a regular basis. At the end of the study period, the animals were sacrificed and subject to macroscopic examination. Mortalities occurred at the 5372 ppm (all animals died), 3547 ppm (all animals died) and 2798 ppm (2/5 males; 5/5 females) concentrations in both male and female animals Clinical signs included perinasal, encrustation, unkempt fur, hypoactivity, blepharospasm, lacrimation, respiratory difficulties (mouth breathing, audible respiration, decreased respiration rate), ataxia, prostration, tremors, distended stomachs, a negative surface and air righting reflex, and negative toe and tail pinch reflex. Two males and four females of the 5372 ppm exposure group had eye opacities with three males and five females also having gas-filled stomachs. There were no other gross lesions in any of the other exposure groups.

Three reliability 4 studies were also available which support the key findings (Dow Corning Corporation 1973; Bushy Run Research Center, 1984; Smyth, 1969).

In the acute dermal toxicity study, conducted according to a protocol similar to OECD Test Guideline 402 but not in compliance with GLP, an LD50 (rabbit) values of 3.36 ml/kg bw for females and 4 ml/kg bw for males (equivalent to 3158 and 3760 mg/kg bw, respectively, based on relative density of 0.94 g/cm³) were determined (Bushy Run Research Centre, 1984b). In the study, doses of 8.0, 4.0 and 2.0 ml/kg bw undiluted test material, trimethoxy(vinyl)silane, were applied onto the skin of male and female rabbits under occlusive dressing for 24 hours. Following application, the animals were observed for 14 days. Body weights and clinical signs were recorded on a regular basis. At the end of the study period, the animals were sacrificed and subject to macroscopic examination. Deaths occurred in 4/5 males and 3/3 females at 8 ml/kg bw; 2/5 males and 3/5 females at 4 ml/kg bw; 2/5 males and 1/5 females at 2 ml/kg bw. Most deaths occurred at one to 5 days (one rabbit died at 8 days).   

Signs of local dermal irritation were reported, and clinical signs of toxicity included discomfort, sluggishness, unsteady gait and prostration. At necropsy, lungs were red and mottled, and some livers were mottled with hard red of white foci.

An acute dermal LD50 value of 3.54 ml/kg bw (equivalent to 3434 mg/kg bw) was determined for rabbits in a study which did not meet current guideline requirements for OECD and which was not in compliant with GLP) (Mellon Institute, 1962).

A reliability 4 study was also available (Witco, 1996), which supports the key findings.

Justification for classification or non-classification

Based on the available data trimethoxy(vinyl)silane requires classification for acute inhalation toxicity as Acute Toxicity Category 4 (vapour): H332: Harmful if inhaled, according to Regulation (EC) No 1272/2008. Classification for acute oral and dermal toxicity is not required.