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Description of key information

In the key skin irritation/corrosion study, conducted according to a protocol similar to OECD Test Guideline 404 and in compliance with GLP (Bushy Run Research Center, 1995d) 3-(trimethoxysilyl)propyl isocyanate was corrosive after a 4-hour, 1-hour and 3-minute occlusive exposure to rabbits. The occlusive dressing might have exaggerated the effects, but the severe effects were observed after a 3-minute exposure, and are therefore likely to occur after a four hour semi-occlusive exposure. 

In the key eye irritation/corrosion study conducted according to OECD Test Guideline 405 and in compliance with GLP (Bushy Run Research Center, 1995e) 3-(trimethoxysilyl)propyl isocyanate caused irreversible effects on the eyes of rabbits.

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:
28.06.1994 to 16.08.1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HRP, Inc (Denver, PA)
- Age at study initiation: 13-18 weeks
- Weight at study initiation: 2-2.3 kg
- Fasting period before study: No
- Housing: Individually in cages with wire floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 40-60
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28.06.1994 To: 16.08.1994
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml
- Concentration: neat
Duration of treatment / exposure:
4-h contact in main study. Also 1-h and 3-minute exposure
Observation period:
14 days
Number of animals:
Because of the potential for the test substance to produce severe skin irritation, Y-5187 was first applied to 2 rabbits (1 male and 1 female)
4-hour contact period. Severe irritation (including full-thickness necrosis) was produced on both rabbits; therefore, an additional 6 rabbits (3 males, 3
females) were included in a 1-hour test. Because full-thickness necrosis was again observed on most rabbits, another 6 rabbits (3 males, 3 females) were
included in a 3-minute skin irritation test.
Details on study design:
TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: No data
- Type of wrap if used: Occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: derivation of PII suggests the use of scoring according Draize for erythema and eschar (max 4) and oedema (max 4). The average score at 24 h and 72 h for all animals giving the PII.
Irritation parameter:
erythema score
Remarks:
4-hour contact
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
4-hour contact
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
4-hour contact
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
4-hour contact
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour contact
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour contact
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour contact
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour contact
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour contact
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
1-hour contact
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.66
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour contact
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour contact
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour contact
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour contact
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour contact
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
1-hour contact
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-minute contact
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-minute contact
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-minute contact
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-minute contact
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-minute contact
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3-minute contact
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-minute contact
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-minute contact
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-minute contact
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-minute contact
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-minute contact
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
3-minute contact
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
4-hour contact period: moderate or severe erythema was produced on 2 of 2 rabbits. Severe edema was observed on both rabbits. At 1 hour after the end of the contact period, ecchymosis was apparent on 1 rabbit. Both rabbits exhibited superficial necrosis at 24 or 72 hours which developed into full thickness necrosis on each by their subsequent examination periods (48 hours or 7 days). Fissuring was observed on 1 rabbit at 7 days. Within 14 days, both animals had scabs; 1 also developed desquamation and alopecia. Erythema persisted on both rabbits through 14 days, but edema was only apparent on 1 at this time. Full-thickness necrosis remained on both rabbits through 14 days.

1-hour contact period: produced moderate erythema and severe edema on 6 of 6 rabbits. Superficial necrosis developed on 5 rabbits within 48 hours to 7
days. Full-thickness necrosis was observed on 4 rabbits by 7 to 14 days. By 14 days, 5 rabbits developed fissuring, 5 had alopecia and scabs, and all 6
developed desquamation. There was no edema on any rabbit at this time. Erythema subsided on 2 rabbits by 14 days. Full-thickness (on 4) or superficial (on 2) necrosis persisted at 14 days.

3 minute contact period: moderate erythema on 6 of 6 rabbits dosed. Moderate to severe edema was also observed on all 6 animals. Ecchymosis developed on 3 animals at 24 to 72 hours. Within 72 hours to 7 days, 4 rabbits had superficial necrosis and 2 had full-thickness necrosis. At 14 days, 1 developed fissuring. Desquamation was apparent on all 6 rabbits at this time. Four rabbits also developed scabs and alopecia. Erythema, edema and superficial necrosis persisted at 14 days. There was no full-thickness necrosis evident on any animal at this time.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
In a skin irritation/corrosion study conducted using a protocol comparable with OECD 404 and in compliance with GLP (reliability score 1) 3-(trimethoxysilyl)propyl isocyanate was corrosive after a 4-hour, 1-hour and 3-minute occlusive exposure to rabbits. The occlusive dressing might have exaggerated the effects, but the severe effects were observed after a 3 minute exposure, and are therefore likely to occur after a four hour semi-occlusive exposure. However, the classification category 1B is most appropriate.
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:
28.06.1994 to 13.09.1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: HRP, Inc (Denver, PA)
- Age at study initiation: 13-18 weeks
- Weight at study initiation: 2-2.3 kg
- Fasting period before study: No
- Housing: Individually in cages with wire floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 40-60
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28.06.1994 To: 13.09.1994
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 or 0.01 ml
Duration of treatment / exposure:
N/A
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
The dose was first instilled into the lower conjunctival sac of a total of only 2 rabbits (both males) because of the potential of the test substance to produce severe ocular injury. The undosed eye of each animal served as the control. Severe ocular injury was produced; therefore, a total of 6 rabbits (3 males, 3 females) were administered 0.01 ml of Y-5187 (applied directly to the cornea).
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Remarks:
Grade 2 on Day 21.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Remarks:
Grade 2 on day 21
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Remarks:
Grade 1 on Day 21.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Remarks:
Grade 1 on Day 21
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Remarks:
Grade 1 on Day 21.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 Days
Remarks on result:
positive indication of irritation
Remarks:
Grade 1 on Day 21.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
positive indication of irritation
Remarks:
Grade 3 on Day 21.
Irritant / corrosive response data:
Severe corneal injury was produced in 2 of 2 rabbits following the instillation of 0.1 ml of Y-5187 into rabbit eyes. Iritis and severe conjunctival irritation were also observed in both eyes. Within 48 hours, both rabbits developed haemorrhages of the nictitating membrane. Necrosis of the conjunctivae, necrosis of the nictitating membrane and a pus-like ocular discharge developed in both dosed rabbit eyes at 48 to 72 hours. At 72 hours, corneal vascularization was evident in each dosed eye. Both rabbits had alopecia or desquamation of the periocular area by 10 or 14 days, respectively. Two rabbits had an abnormal corneal shape (characterized by surface bulging) at 14 and/or 21 days. Haemorrhages of the conjunctivae and periocular encrustation were also observed on 1 at 17 days. Within 21 days, scabs were present on the periocular area of 1 animal. Both rabbits had severe ocular irritation through 21 days.

Following the instillation of 0.01 ml of the test substance, minor to moderate corneal injury, iritis and severe conjunctival irritation were apparent in 6 of 6 rabbit eyes. A pus-like ocular discharge was evident in all 6 dosed eyes within 24 to 48 hours. By 48 to 72 hours, necrosis of the nictitating membrane was observed in 5. Three rabbits had necrosis of the conjunctivae at 48 to 72 hours. Haemorrhages of the nictitating membrane were observed in all 6 dosed eyes within 48 hours to 7 days. By 7 days, corneal vascularization was evident in 2 rabbits. Each rabbit had periocular alopecia (around the dosed eye) within 7 to 14 days. Apparent ulceration was observed on the inside of the lower conjunctivae area of 1 rabbit at 14 days and persisted through 21 days. One eye was healed by 14 days; however, periocular alopecia was evident for this rabbit at 17 days. Three additional rabbits had a normal ocular appearance within 21 days. Severe ocular irritation was evident in 2 of 6 rabbits through 21 days.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an eye irritation/corrosion study conducted to OECD 405 and to GLP (reliability score 1) 3-(trimethoxysilyl)propyl isocyanate caused irreversible effects on the eyes of rabbits.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for skin irritation/corrosion (Bushy Run Research Center, 1995d), conducted according to OECD 404 and in compliance with GLP, found 3-(trimethoxysilyl)propyl isocyanate to be corrosive after a 4-hour, 1-hour and 3-minute occlusive exposure to rabbits. The occlusive dressing may have resulted in more pronounced effects, but the severe effects were observed after a 3-minute exposure, and are therefore likely to also be present after a 4-hour semi-occlusive exposure. However, the classification category 1B is the most appropriate.

Moderate to severe edema was observed in all dosed animals. Within 72 hours to 7 days, 4 rabbits had superficial necrosis and 2 had full-thickness necrosis. Desquamation was apparent in all animals at this time. Four rabbits also developed scabs and alopecia. Erythema, edema and superficial necrosis persisted until day 14. There was no full-thickness necrosis evident on any animal at this time.

The key study for eye irritation/corrosion, conducted according to current guideline and in compliance with GLP, reports 3-(trimethoxysilyl)propyl isocyanate to cause irreversible effects on the eyes of rabbits (Bushy Run Research Center, 1995e).

Severe corneal injury was produced in rabbits following the instillation of the test substance into rabbit eyes. Iritis and severe conjunctival irritation were observed in both eyes. Within 48 hours, both rabbits developed haemorrhages of the nictitating membrane. Necrosis of the conjunctivae, necrosis of the nictitating membrane and a pus-like ocular discharge developed in both dosed rabbit eyes at 48 to 72 hours. At 72 hours, corneal vascularization was evident in each dosed eye. Both rabbits had alopecia or desquamation of the periocular area by 10 or 14 days, respectively. The rabbits also presented an abnormal corneal shape (characterized by surface bulging) at 14 and/or 21 days. Haemorrhages of the conjunctivae and periocular encrustation were also observed on 1 at 17 days. Within 21 days, scabs were present on the periocular area of 1 animal. Both rabbits had severe ocular irritation through 21 days.

Data for the hydrolysis product, 3-(trimethoxysilyl)propylamine (CAS 13822-56-5), have been added to the dataset as supporting information for completeness, but are not required for the assessment of the skin and eye irritation potential of the parent as reliable data for it are available.


Justification for classification or non-classification

Based on the available data, 3-(trimethoxysilyl)propyl isocyanate is classified for skin corrosion Cat. 1B, H314: "Causes severe skin burns and eye damage" according to Regulation (EC) No 1272/2008. The skin irritation/corrosion data show that the test substance is clearly corrosive to the skin. It is assumed that substances that are corrosive to the skin are also damaging to the eyes, so there is no separate labelling for the eyes. Available eye irritation data show this classification to be reasonable.