Trimethoxysilane

Endpoint summary

Description of key information

In the key skin irritation study (BRRC, 1988), conducted using a protocol similar to OECD Test Guideline 404 but with no mention of GLP, undiluted trimethoxysilane was corrosive to the skin of rabbits (strain not given) after a four-hour exposure under occlusive conditions.

The key eye irritation study (BRRC, 1988), which was similar to OECD Test Guideline 405 but with no mention of GLP, showed undiluted trimethoxysilane to be irritating to the eyes of rabbits (strain not given).

Acute inhalation and repeated dose inhalation studies indicate that this test substance is irritating/corrosive to the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. No mention of GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

Four hours

Observation period:

14 days

Number of animals:

Six

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 48 and 72 hrs

Score:

6.53

Remarks on result:

other: PII (24-, 48- and 72-hour scores for erythema/eschar and edema formation) = 6.53

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

87-29367

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

87-29373

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

The dose site of this rabbit could not be scored until 2 days because the gauze patch (used in dose application) had completely adhered to the skin.

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

87-28182

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

87-29397

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

87-29400

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

87-29402

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

87-29367

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

87-29373

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

The dose site of this rabbit could not be scored until 2 days because the gauze patch (used in dose application) had completely adhered to the skin.

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

87-28182

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

87-29397

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

87-29400

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

87-29402

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

A 4-hour application of 0.5 ml of trimethoxysilane to occluded rabbit skin resulted in moderate to severe erythema, severe edema and necrosis on 6 of 6 rabbits.  Ecchymoses were present on the dose site of 3 animals.  
The dose site of one rabbit could not be scored until 2 days because the gauze patch (used in dose application) had completely adhered to the skin.  Four rabbits exhibited fissuring within 3 days.  Erythema was no longer present on any of 6 animals at 7 days and edema was no longer observed after 14 days.  However, desquamation, ulceration, scabs and alopecia developed on all rabbits within 7 to 14 days.  Thus, severe irritation was present through 14 days.  Two animals were found dead at 12 days.  There was no indication that these deaths were related to the dose, although they could have resulted from a secondary infection.

Other effects:

Two animals were found dead at 12 days. There was no indication that these deaths were related to the dose, although they could have resulted from a secondary infection.

	Mean Erythema Score	Mean Edema Score
5 hrs	3.0	3.2
1 day	3.0	3.6
2 days	2.7	4.0
3 days	2.3	4.0
7 days	0	0.8
10 days	0	0.3
14 day	0	0

A 4-hour application of 0.5 ml of trimethoxysilane to occluded rabbit skin resulted in moderate to severe erythema, severe edema and necrosis on 6 of 6 rabbits. Ecchymoses were present on the dose site of 3 animals. The dose site of one rabbit could not be scored until 2 days because the gauze patch (used in dose application) had completely adhered to the skin. Four rabbits exhibited fissuring within 3 days. Erythema was no longer present on any of 6 animals at 7 days and edema was no longer observed after 14 days. However, desquamation, ulceration, scabs and alopecia developed on all rabbits within 7 to 14 days. Thus, severe irritation was present through 14 days.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In a skin irritaton study (reliability score 2), conducted using a protocol similar to OECD Test Guideline 404 but with no mention of GLP, trimethoxysilane was corrosive to the skin of rabbits after a four hour exposure.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. No mention of GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1, 0.01 or 0.005 ml

Duration of treatment / exposure:

Eyes were not washed

Observation period (in vivo):

Seven days

Number of animals or in vitro replicates:

Six per dose volume

Details on study design:

Six rabbits were dosed with 0.1 ml.  Six rabbits were dosed with 0.01 ml.  Six rabbits were dosed with 0.005 ml. Eyes were not rinsed

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

87-29376

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

0.1 mL

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

87-29377

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

87-23978

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

0.1 mL

Irritation parameter:

cornea opacity score

Basis:

animal #4

Remarks:

87-29415

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

cornea opacity score

Basis:

animal #5

Remarks:

87-29416

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

0.1 mL

Irritation parameter:

cornea opacity score

Basis:

animal #6

Remarks:

87-29417

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

0.1 mL

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

87-29376

Time point:

24/48/72 h

Score:

0.66

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

87-29377

Time point:

24/48/72 h

Score:

0.66

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

87-23978

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

iris score

Basis:

animal #4

Remarks:

87-29415

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

0.1 mL

Irritation parameter:

iris score

Basis:

animal #5

Remarks:

97-29416

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

0.1 mL

Irritation parameter:

iris score

Basis:

animal #6

Remarks:

87-29417

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

87-29376

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

87-29377

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

87-23678

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Remarks:

0.1mL

Irritation parameter:

conjunctivae score

Basis:

animal #4

Remarks:

87-29415

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

0.1 mL

Irritation parameter:

conjunctivae score

Basis:

animal #5

Remarks:

87-29416

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

0.1 mL

Irritation parameter:

conjunctivae score

Basis:

animal #6

Remarks:

87-29417

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

87-29376

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

87-29377

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

87-23978

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

87-29415

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

chemosis score

Basis:

animal #5

Remarks:

87-29416

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritation parameter:

chemosis score

Basis:

animal #6

Remarks:

87-29417

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Remarks:

0.1 mL

Irritant / corrosive response data:

See Table 1 for summary of results. Instillation of 0.1 ml of sample into rabbit eyes resulted in minor corneal injury (opacity) in 3/6 animals.  Iritis and moderate to severe conjunctival irritation (including necrosis in 5) were observed in all 6 animals.  All rabbits had a purulent ocular discharge. Except for alopecia in the periocular area of each dosed eye and a substantial discharge in one eye, all eyes appeared to be essentially healed by 7 days. Alopecia was still evident on each rabbit at 14 days,  but no other effects were observed.

Table 1 Summary of results for 0.1ml instillation (volume specified in OECD 405), mean scores

	1 h	4 h	24h	48 h	72 h	7 days	14 days
Cornea
Opacity	0.5	0.5	0.5	0.2	0.2	0	0
Area	0.5	0.5	0.5	0.2	0.2	0	0
Iris
Inflam.	0.8	0.8	1.0	0.7	0.3	0	0
Conjunct.
Redness	2.0	2.0	2.2	1.5	1.2	0	0
Chemosis	2.0	2.3	1.5	0.5	0.3	0	0
Discharge	3.0	3.0	3.0	1.3	1.5	0.5	0

After doses of 0.01 ml were applied directly on the cornea, 5/6 eyes developed minor to moderate corneal opacity.  Iritis and moderate to severe conjunctival irritation (with necrosis in 3) was apparent in all 6 rabbits. A purulent discharge was evident in 5/6 eyes. By 24 hours, one rabbit exhibited hemorrhaging of the nictitating membrane.  Two eyes appeared normal at 48 hours. Two others had only slight conjunctival irritation. Four eyes were healed at 72 hours and the other 2 developed a normal appearance by 7 days.

Table 2 Summary of results for 0.01ml instillation, mean scores

	1 h	4 h	24h	48 h	72 h	7 days
Cornea
Opacity	0.7	1.0	0.3	0.2	0	0
Area	0.7	1.0	0.5	0.2	0	0
Iris
Inflam.	0.7	1.0	0.8	0.3	0	0
Conjunct.
Redness	1.5	2.0	1.5	0.8	0.3	0
Chemosis	1.0	2.0	1.0	0.3	0	0
Discharge	2.0	2.5	1.7	0.7	0.2	0

No corneal injury was apparent after the administration of 0.005 mL of sample into rabbit eyes. Iritis developed in 4/6 rabbits. Minor to severe conjunctival irritation (with necrosis in 4) was observed in 6/6 animals. One eye appeared normal at 48 hours and 5 exhibited only slight conjunctival irritation. By 72 hours, all eyes were healed. One rabbit was found dead at 6 days with no indication that the death was dose-related.

Table 3 Summary of results for 0.005 ml instillation, mean scores

	1 h	4 h	24h	48 h	72 h
Cornea
Opacity	0.0	0.0	0.0	0.0	0.0
Area	0.0	0.0	0.0	0.0	0.0
Iris
Inflam.	0.5	0.7	0.3	0.3	0.0
Conjunct.
Redness	1.0	1.2	1.0	0.8	0.0
Chemosis	1.0	1.3	0.3	0.0	0.0
Discharge	1.0	2.8	0.3	0.2	0.2

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an eye irritation study (reliability score 2) conducted using a protocol similar to OECD Test Guideline 405 but with no mention of GLP, 0.1 ml trimethoxysilane was moderately irritating to the eyes of rabbits.

Executive summary:

In an eye irritation study (reliability score 2) conducted using a protocol similar to OECD Test Guideline 405 but with no mention of GLP, trimethoxysilane was instilled into one eye of each of six rabbits per dose (0.1, 0.01 and 0.005 ml). The animals were then observed for seven days. Since it is a volume of 0.1 ml that is recommended by OECD Test Guideline 405, only the results from this dose group are included in this summary: minor corneal opacity in 3/6 animals. 

Iritis and moderate to severe conjunctival irritation (including necrosis in five) were observed in all six animals.

All rabbits had a purulent ocular discharge. Except for alopecia in the periocular area of each dosed eye and a substantial discharge in one eye, all eyes appeared to be essentially healed by seven days. Alopecia was still evident in each rabbit on day 14 but no other effects were observed. It was concluded that trimethoxysilane was moderately irritating to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

For skin irritation the most reliable study was used as the key study. All supporting studies were reliability 4.

In the key study (reliability score 2), conducted using a protocol similar to OECD Test Guideline 404 but with no mention of GLP, a 4-hour application of 0.5 ml  of trimethoxysilane to occluded rabbit skin resulted in moderate to severe erythema, severe edema and necrosis on 6 of 6 rabbits.  Ecchymoses were present on the dose site of 3 animals.

The dose site of one rabbit could not be scored until after 2 days because the gauze patch (used in dose application) had completely adhered  to the skin. Four rabbits exhibited fissuring within 3 days.  Erythema was no longer present on any of 6 animals at 7 days and edema  was no longer observed after 14 days.  However, desquamation, ulceration, scabs and alopecia developed on all rabbits within 7 to 14 days. Thus, severe irritation was present through 14 days. Two animals were found dead at 12 days. There was no indication that these deaths were related to the dose, although they could have resulted from a secondary infection (BRRC, 1998).

It was concluded that trimethoxysilane was corrosive to the skin of rabbits.

For eye irritation there were three reliability score 2 studies. The most recent of these was selected as the key study. Most studies were supportive of the key study findings. Where they were not, there were methodological or reporting deficiencies.

In the key eye irritation study (reliability score 2) conducted using a protocol similar to OECD Test Guideline 405 but with no mention of GLP, trimethoxysilane was instilled into one eye of each of six rabbits per dose (0.1, 0.01 and 0.005 ml). The animals were then observed for seven days. Since it is a volume of 0.1 ml that is recommended by OECD Test Guideline 405, only the results from this dose group are included in this summary: minor corneal opacity in 3/6 animals. Iritis and moderate to severe conjunctival irritation (including necrosis in five) were observed in all six animals.

All rabbits had a purulent ocular discharge. Except for alopecia in the periocular area of each dosed eye and a substantial discharge in one eye, all eyes appeared to be essentially healed by seven days. Alopecia was still evident in each rabbit on day 14 but no other effects were observed (BRRC, 1988).

It was concluded that trimethoxysilane was moderately irritating to the eyes of rabbits.

Justification for classification or non-classification

The proposed hazard class for trimethoxysilane under Regulation (EC) No 1272/2008 is 'Skin Corr. 1C' and hence 'H314: Causes severe skin burns and eye damage'.