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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:
6 - 21 Nov 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Feb 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Jan 1997
Deviations:
no
GLP compliance:
yes
Remarks:
Ministry of Agriculture, Environmental Protection and Regional Planning, Potsdam, Germany

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
other: Chbb:HM(SPF) - Littlerussian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 - 2.1 kg
- Housing: individually in PPO cages (floor area: 2576 cm²) with perforated floor
- Diet: Altromin 2123 (Altromin, Lage, Germany), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Reading time points: 1, 24, 48 and 72 hours and 7 days after treatment
Number of animals or in vitro replicates:
4 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: 20 mL 0.9% sodium chloride solution was used
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize scoring system

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:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
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:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal: #1, #3 and #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal: #2 and #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
One hour after application of the test substance animal No. 1 showed easily discernible translucent areas with slightly obscured details of iris on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse beefy red conjunctiva, a swelling with lids more than half closed and a discharge with moistening of the lids and hairs, and considerable area around the eye. In animal No. 2 a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible, an obvious swelling with partial eversion of lids and a discharge with moistening of the lids and hairs, and considerable area around the eye were observed. Animal No.3 showed easily discernible translucent areas with slightly obscured details of iris on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse beefy red conjunctiva, a swelling with lids about half closed and a discharge with moistening of the lids and hairs, and considerable area around the eye. In animal No. 4 a scattered or diffuse area of opacity on more than one quarter, but less than half, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction lights, a diffuse beefy red conjunctiva, a swelling with lids about half closed and a discharge with moistening of the lids and hairs, and considerable area around the eye were observed.

24 hours after application of the test substance animal No. 1 showed a scattered or diffuse area of opacity on more than three quarters of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse beefy red conjunctiva, a swelling with lids about half closed and a discharge different from normal. In animal No. 2 a scattered or diffuse area of opacity on one quarter or less of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as a swelling above normal were observed. Animal No. 3 showed easily discernible translucent areas with slightly obscured details of iris on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse beefy red conjunctiva, a swelling with lids about half closed and a discharge with moistening of the lids and hairs just adjacent to lids. In animal No. 4 a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse beefy red conjunctiva, an obvious swelling with partial eversion of lids and a discharge different from normal were observed. After instillation of fluorescein animal No. 1 showed a scattered or diffuse area of opacity on more than three quarters of the cornea. A scattered or diffuse area of opacity was observed on one quarter or less of the cornea in animal No. 2 and on more than half, but less than three quarters of the cornea in animal No. 3. Animal No. 4 showed a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea.

48 hours alter application of the test substance in animal No. 1 showed a scattered or diffuse area of opacity on more than three quarters of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as an obvious swelling with partial eversion of lids. In animal No. 2 an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as a swelling above normal were observed. In animal No. 3 a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse beefy red conjunctiva, an obvious swelling with partial eversion of lids and a discharge with moistening of the lids and hairs just adjacent to lids were observed. Animal No. 4 showed a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible, an obvious swelling with partial eversion of lids and a discharge different from normal. After instillation of fluorescein in animal No. 1 a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, was observed. Animals No. 3 and No. 4 showed a scattered or diffuse area of opacity on one quarter or less of the cornea.

At 72 hours an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as an obvious swelling with partial eversion of lids were observed in animal No. 1. Animal No. 2 showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible as well as a swelling above normal. In animal No. 3 a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible, a swelling above normal and a discharge different from normal were observed. Animal No. 4 showed a scattered or diffuse area of opacity on more than one quarter, but less than half of the cornea, an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, some conjunctival vessels definitely injected and a swelling above normal. After instillation of fluorescein in animal No. 1 a scattered or diffuse area of opacity on one quarter or less of the cornea was observed.

7 days after application of the test substance all four animals were free of any signs of eye Irritation.

Any other information on results incl. tables

Table 1. Results of the eye irritation study

Animal

Time (h)

Conjunctivae

Cornea

Iris

Redness

Chemosis

1

1

3

4

2

1

24

3

3

1

1

48

2

2

1

1

72

2

2

0

1

Average 24+48+72

2.3

2.3

0.7

1.0

2

1

2

2

1

1

24

2

1

1

1

48

2

1

0

1

72

2

1

0

0

Average 24+48+72

2.0

1.0

0.3

0.7

3

1

3

3

2

1

24

3

3

2

1

48

3

2

1

1

72

2

1

1

1

Average 24+48+72

2.7

2.0

1.3

1.0

4

1

3

3

1

1

24

3

2

1

1

48

2

2

1

1

72

1

1

1

1

Average 24+48+72

2.0

1.7

1.0

1.0

Applicant's summary and conclusion

Interpretation of results:
other: Eye Irrit. Cat. 2 according to Regulation (EC) 1272/2008
Conclusions:
Under the conditions of this eye irritation study in rabbits the test substance was irritating to the eye.
Executive summary:

The individual mean scores after 24, 48 and 72 h are for corneal opacity 0.7, 0.3, 1.3, 1.0, for iris lesion 1.0, 0.7, 1.0, 1.0, for conjunctival redness 2.3, 2.0, 2.7, 2.00 and for chemosis 2.3, 1.0, 2.0, 1.7. All ocular lesions were fully reversible within 7 days. Therefore, the test substance is considered to be irritating to the eye.