Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 13 and February 3, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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: Davidson's Mill Farm, South Brunswick, NJ
- Housing: individually in suspended stainless steel caging mesh floors
- Diet: Pelleted Purina Rabbit Chow #5326
- Water: ad libitum (tap water)
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 21.7
- Photoperiod (hrs dark / hrs light): 12/12


Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: left eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
3 animals: washed after 20-30 seconds
(6 animals: unwashed)
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 washed (+6 unwashed)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Yes, at 3 of 9 animals
- Time after start of exposure: 20-30 seconds

SCORING SYSTEM: According to Draize scheme

TOOL USED TO ASSESS SCORE: hand-slit lamp / 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
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 17 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Within 24 hours of test substance instillation, all unwashed eyes exhibited corneal opacity, iritis and conjunctivitis. Overall, the incidence and severity of irritation decreased with time. Although iritis cleared from all eyes by day 17, conjunctivitis, pannus and/or corneal opacity persisted in 2 animals through day 21.
Other effects:
- Lesions and clinical observations: There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.
- Other observations: Twenty four hours after test substance instillation, all washed eyes exhibited conjunctivitis and iritis and corneal opacity were noted in one and two animals, respectively. The incidence and severity of irritation decreased with time. Iritis and corneal opacity cleared from all affected rabbits by 72 hours and day 4, respectively and all animals were free from ocular irritation by day 7.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the results of a primary eye irritation test, the test item is considered to be irritating to rabbits' eye.
Executive summary:

A Primary Eye Irritation test was conducted with rabbits to determine the potential for the test item to produce irritation and/or corrosion via the ocular route. One-tenth of a milliliter of the test substance was instilled into one eye of nine healthy rabbits.The other eye remained untreated with the test substance and served as a control. The treated eyes of three rabbits were washed after instillation of the test substance. The eyes ol the remaining six rabbits were not washed.Ocular irritation was evaluated by the method of Draize et al. The eye scores were further classified by the system of Kay and Calandra (modified).

 

Within 24 hours of test substance instillation, all unwashed eyes exhibited corneal opacity, iritis and conjunctivitis. Overall, the incidence and severity of irritation decreased with time. Although iritis cleared from all eyes by day 17, conjunctivitis, pannus and/or corneal opacity persisted in 2 animals through day 21.

Twenty four hours after test substance instillation, all washed eyes exhibited conjunctivitis and iritis and corneal opacity were noted in one and two animals, respectively, The incidence and severity of irritation decreased with time. By day 7, all animals were free from ocular irritation.

 

Only data for the unwashed eyes were taken into account for the evaluation and classification as irritanting or non-irritanting to eye. The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for cornea opacity were 1.0, 1.0, 1.0, 1.0, 1.0 and 1.0, respectively. For iris, the individual mean scores were 0.3, 0.0, 1.0, 0.0, 1.0, and 1.0, respectively. The individual mean scores for conjunctivae were 3.0, 3.0, 2.6, 2.6, 3.0 and 2.3, respectively. The individual mean chemosis scores were 3.0, 3.0, 3.0, 2.6, 3.0 and 2.3, respectively.

Based on the results, the test item is considered to be irritating to rabbits' eye.