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Toxicological information

Eye irritation

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Administrative data

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

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 405 (Acute Eye 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 / tissue source

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

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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.

Applicant's summary and conclusion

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.