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Skin irritation / corrosion

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Administrative data

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

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995
Reference Type:
other: Summary of toxicological data
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(trimethoxysilyl)propyl isocyanate
EC Number:
239-415-9
EC Name:
3-(trimethoxysilyl)propyl isocyanate
Cas Number:
15396-00-6
Molecular formula:
C7H15NO4Si
IUPAC Name:
(3-isocyanatopropyl)(trimethoxy)silane
Test material form:
liquid

Test animals

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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Applicant's summary and conclusion

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.