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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Testing procedures do not follow an official European testing guideline, nevertheless they are well documented and scientifically acceptable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Principles of method if other than guideline:
The procedure used is based, but not in every part identical with the Proposed Guidelines of the United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study".
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: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf.
- Weight at study initiation: 2-3 kg.
- Housing: individually in metal cages.
- Diet: rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), ad libitum.
- Water: water ad libitum.
- Acclimation period: 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C.
- Humidity: 55 ± 15 %.
- Air changes: 15 air changes/h.
- Photoperiod: 12 hours light/day.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
- Concentration: undiluted.

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:
6 (3 male and 3 female).
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:
animal: 6/6
Time point:
other: mean 24, 48, 72 hours
Score:
< 1
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritation parameter:
iris score
Basis:
animal: 6/6
Time point:
other: mean 24, 48, 72 hours
Score:
< 1
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritation parameter:
conjunctivae score
Basis:
animal: 6/6
Time point:
other: mean 24, 48, 72 hours
Score:
< 2
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritation parameter:
chemosis score
Basis:
animal: 6/6
Time point:
other: mean 24, 48, 72 hours
Score:
< 2
Reversibility:
fully reversible
Remarks on result:
other: rinsed and unrinsed eyes
Irritant / corrosive response data:
Test substance was found to cause minimal irritation when applied to the rabbit eye mucosa.

Any other information on results incl. tables

Non-washed eye results

Exposure Cornea Iritis Conjunctival
redness chemosis

Animal no. 1 (eyes not washed out)

24 hrs 0 0 0 1
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0

Mean 24, 48, 72 hrs

0.00 0.00 0.00 0.33

Animal no. 2 (eyes not washed out)

24 hrs 0 0 1 0
48 hrs 0 0 1 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0

Mean 24, 48, 72 hrs

0.00 0.00 0.67 0.00

Animal no. 3 (eyes not washed out)

24 hrs 0 0 1 0
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0

Mean 24, 48, 72 hrs

0.00 0.00 0.33 0.00

Washed eye results

Exposure Cornea Iritis Conjunctival
redness chemosis

Animal no. 1 (eyes washed out)

24 hrs 0 0 1 0
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0
Mean 24, 48, 72 hrs 0.00 0.00 0.33 0.00

Animal no. 2 (eyes washed out)

24 hrs 0 0 0 0
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0
Mean 24, 48, 72 hrs 0.00 0.00 0.00 0.00

Animal no. 3 (eyes washed out)

24 hrs 0 0 0 1
48 hrs 0 0 0 0
72 hrs 0 0 0 0
4 days 0 0 0 0
7 days 0 0 0 0
Mean 24, 48, 72 hrs 0.00 0.00 0.00 0.33

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
Not irritating
Executive summary:

Method

The eye irritation potential was assessed on the basis of the procedures reported in the Proposed Guidelines of the United States Environmental Protection Agency (EPA) Paragraph 163.81-5 "Primary eye irritation study", Federal Register, Vol. 43 No. 163 August 22, 1978.

Results

Under the conditions the test substance was found to cause minimal irritation when applied to the rabbit eye mucosa.

The calculated primary irritation index were: 0.8 in unrinsed eyes and 0.3 in rinsed eyes.

Discussion and 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 (EC 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.

In conclusion, the test item can be classified as NON irritating, according to the CLP (EC 1272/2008) Regulation.