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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:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
However, the substance concentration was low in the lot tested.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report date:
1974

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO)
GLP compliance:
no
Remarks:
pre GLP

Test material

Constituent 1
Reference substance name:
Direct Blue 199 Na
IUPAC Name:
Direct Blue 199 Na

Test animals / tissue source

Species:
rabbit
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Russian breed
- Housing: the rabbits were kept separately in V2A wire cages.
- Diet: ad libitum, NAFAG, Gossau SG, rabbit food.
- Water: ad libitum.
Only rabbits showing normal ophthalmic findings were included in the test.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 animals: 3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the treated eyes of three rabbits were each rinsed with 10 ml lukewarm water.
- Time after start of exposure: about 30 seconds after treatment.

TOOL USED TO ASSESS SCORE: hand-slit lamp, after 24 hours and after 2, 3, 4 and 7 days.

SCORING SYSTEM: the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.
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

IRITIS:
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 lids 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 cantus 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
Remarks:
both rinsed and unrinsed eyes
Time point:
24/48/72 h
Score:
< 1
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: 6/6
Remarks:
both rinsed and unrinsed eyes
Time point:
24/48/72 h
Score:
< 1
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: 6/6
Remarks:
both rinsed and unrinsed eyes
Time point:
24/48/72 h
Score:
< 2
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: 6/6
Remarks:
both rinsed and unrinsed eyes
Time point:
24/48/72 h
Score:
< 2
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The irritation index was found to be 0 for the cornea, 0 the iris and 0.2 for the conjunctivae.

Any other information on results incl. tables

Eyes rinsed

Days after
Appl.
Rabbit 1, female Rabbit 2, female Rabbit 3, female
Cornea Iritis Conjunct. Cornea Iritis Conjunct. Cornea Iritis Conjunct.
1 0 0 0 0 0 0 0 0 0
2 0 0 0 0 0 0 0 0 0
3 0 0 0 0 0 0 0 0 0
4 0 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0 0

Eyes not rinsed

Days after
Appl.
Rabbit 4, male Rabbit 5, male Rabbit 6, male
Cornea Iritis Conjunct. Cornea Iritis Conjunct. Cornea Iritis Conjunct.
1 0 0 6 0 0 0 0 0 0
2 0 0 0 0 0 0 0 0 0
3 0 0 0 0 0 0 0 0 0
4 0 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0 0

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
Not irritating.
Executive summary:

The substance was tested on 6 rabbits (3 males/3 females); amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment. The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

The irritation index was found to be 0 for the cornea, 0 the iris and 0.2 for the conjunctivae.

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 cornea 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).

In spite of the raw tables are not included into the study report, 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 iritis, 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 not classified as irritating, according to the CLP Regulation (EC) No 1272/2008.

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