Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
14 - 21 Dec 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS GmBH, Med. Versuchstierzuchten KG, D-7964 Kisslegg
- Weight at study initiation: 2 to 3 kg
- Housing: individually in metal cages
- Diet: standard rabbit food NAFAG, No. 814 Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: minimum 4 days
Only rabbits with normal ophthalmic findings were used for these tests

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 12 hours light cycle day

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye was not treated and served as an untreated control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
single exposure; in 3 of the 6 rabbits approximately 30 seconds after the treatment the treated eye was washed out
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 females and 3 males
Details on study design:
APPLICATION
The test material was inserted in the conjunctival sac of the left eye of the rabbits and the lids were gently closed for 15 seconds. The right eye was not treated and served as an untreated control.

REMOVAL OF TEST SUBSTANCE
- Washing: with 10 mL of sterile physiological saline.
- Time after start of exposure: in 3 of the 6 rabbits approximately 30 seconds after the treatment the treated eye was flushed.

TOOL USED TO ASSESS SCORE: hand-slit lamp

SCORING SYSTEM
The eye irritation was assessed at 24, 48, 72 hours and 4 and 7 days after treatment.
CORNEA:
A Opacity and degree of density (most dense area scored).
No opacity: 0
Scattered or diffuse area, details of iris clearly visible: 1
Easily discernible translucent areas, details of iris slightly obscured: 2
Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
Opaque, iris invisible: 4
B Area of cornea involved
One quarter (or less) but not zero: 1
Greater than one quarter, but less than half: 2
Greater than half, but less than three quarters: 3
Greater than three quarters, up to whole area: 4
A x B x 5; Maximum possible score = 80

IRIS:
A Values
Normal: 0
Folds above normal, congestion, swelling, circumcornea injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive: 1
No reaction to light, hemorrhage, gross destruction (any or all of these): 2
A x 5; Maximum possible score = 10

CONJUNCTIVAE:
A Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal: 0
Vessels definitely injected above normal: 1
More diffuse, deeper crimson red, individual vessels not easily discernible: 2
Diffuse beefy red: 3
B Chemosis
No swelling: 0
Any swelling above normal (includes nictitating membrane): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids about half closed to completely closed: 4
C Discharge
No discharge: 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs, and considerable area around the eye: 3
(A + B + C) x 2; Maximum possible score = 20

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Other effects:
One animal died 7 days after instillation of the test material and it was stated that no symptoms had been observed prior to death.

Any other information on results incl. tables

Eye reactions

Animal Eye 24 hrs 48 hrs 72 hrs 4 days 7 days Mean 24, 48, 72 hrs

Cornea

144 not rinsed 0 0 0 0 0 0.00
145 not rinsed 0 0 0 0 0 0.00
146 not rinsed 0 0 0 0 0 0.00
147 rinsed 0 0 0 0 / 0.00
148 rinsed 0 0 0 0 0 0.00
149 rinsed 0 0 0 0 0 0.00

Iris

144 not rinsed 0 0 0 0 0 0.00
145 not rinsed 0 0 0 0 0 0.00
146 not rinsed 0 0 0 0 0 0.00
147 rinsed 0 0 0 0 / 0.00
148 rinsed 0 0 0 0 0 0.00
149 rinsed 0 0 0 0 0 0.00

Conjunctivae Redness

144 not rinsed 2 0 0 0 0 0.67
145 not rinsed 0 0 0 0 0 0.00
146 not rinsed 0 0 0 0 0 0.00
147 rinsed 1 0 0 0 / 0.33
148 rinsed 0 0 0 0 0 0.00
149 rinsed 0 0 0 0 0 0.00

Conjunctivae Chemosis

144 not rinsed 0 0 0 0 0 0.00
145 not rinsed 0 0 0 0 0 0.00
146 not rinsed 0 0 0 0 0 0.00
147 rinsed 0 0 0 0 / 0.00
148 rinsed 0 0 0 0 0 0.00
149 rinsed 0 0 0 0 0 0.00

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Method

The test was performed on 3 male and 3 female New Zealand White rabbits. The test material in an amount of 0.1 g was inserted into

the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed.

The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit.

Results

Results

Under the conditions of this experiment the test material was found to cause a minimal irritation when applied to the rabbit eye mucosa.

One animal died at Day 7. No symptoms had been observed previously.

Conclusion

The criteria for the evaluation of the eye irritation potential followed in the test are different from those reported into the OECD guideline. The scoring system used for the corea opacity and degree of density, for the iris and conjunctivae redness and chemosis is the same of that reported into the OECD, but the timing for the removal of the substance are very different (30 seconds in the current study and 1 hours in the OECD). Nevertheless, because the raw tables are included into the study report, it is possible to re-evaluate the results according to the CLP Regulation (1272/2008).

The mean values from gradings at 24, 48 and 72 hours for both rinsed and unrinsed eyes were lower than 1 for corneal opacity, lower than 1 for irtitis, lower than 2 for both conjunctival redness and oedema, in all animals.

Therefore the substance does not meet the criteria to be classified as eye irritating.