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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:
From January 25 to February 05, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline No. 405 without any deviation.

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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
inspected on September 22, 1999 / signed on January 18, 2000

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Physical state: White solid (but some samples were received as liquid, due to stability in supercooled state)
- Storage condition of test material: At room temperature, protected from light and under nitrogen atmosphere


Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Age at study initiation: No data available
- Weight at study initiation: 2.7 ± 0.2 kg
- Housing: Animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: 112 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30–70%
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: January 25, 2000 To: February 05, 2000

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye was untreated, serving as the control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg (ground to a fine powder)


Duration of treatment / exposure:
Single application to the left eye. The eyes were not rinsed after administration of the test substance.
Observation period (in vivo):
Observations at 1, 24, 48 and 72 hours and then daily until reversibility of the ocular reactions. When there was persistent ocular irritation after 72 hours, the observation period was extended to a maximum of 21 days (until day 22) in order to determine the progress of the lesions and their reversibility.
Number of animals or in vitro replicates:
3 male animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: not done. The eyes were not rinsed after administration of the test substance.
- Time after start of exposure: not applicable

SCORING SYSTEM: Draize scale as described in the OECD guideline No. 405.

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:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
probability of mild irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 6 days
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 5 days
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 10 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 11 days
Remarks on result:
probability of severe irritation
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
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 11 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 12 days
Remarks on result:
probability of moderate irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Very slight to moderate conjunctival reactions were observed in all animals from day 1: a very slight to moderate chemosis (grades 1 to 3), a very slight to moderate redness of the conjunctiva (grades 1 to 3) and a clear discharge were noted. These reactions persisted up to day 6, 10 or 11.
A slight iritis (grade 1) was noted in all animals on day 2; it persisted up to day 4, 5 or 6.
A slight corneal opacity (grade 2) was recorded in all animals on day 2; a very slight or slight corneal opacity (grade I or 2) persisted up to day 4 (one animal) or 7.
Neovascularisation was noted in one animal, from day 6 up to day 9.
Other effects:
None

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

2 / 2 / 2

2 / 2 / 2

2 / 2 / 2

24 h

2 / 2 / 2

1 / 1 / 1

3 / 3 / 3

3 / 3 / 3

2 / 2 / 3

48 h

2 / 2 / 2

1 / 1 / 1

3 / 3 / 3

2 / 3 / 2

0 / 1 / 0

72 h

2 / 2 / 2

1 / 1 / 1

3 / 3 / 2

2 / 2 / 2

0 / 0 / 0

Average 24h, 48h, 72h

2 / 2 / 2

1 / 1 / 1

3 / 3 / 2.7

2.3 / 2.7 / 2.3

0.7 / 1 / 0.7

Reversibility*)

c.

c.

c.

c.

c

Average time for reversion

D8 / D8 / D5

D6 / D7 / D5

D10 / D11 / D7

D11 / D12 / D7

48h / 72h / 48h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

D = Day

Applicant's summary and conclusion

Interpretation of results:
irritating
Conclusions:
Under the test conditions, the test material is classified as "Category 2 irritating to eyes" according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an eye irritation study performed according to the OECD Guideline No. 405/EU Method B.5, and in compliance with GLP, asingle dose of 100 mg of the test substance, first ground to a fine powder, was introduced into the conjunctival sac of the left eye of three male New Zealand White rabbits. The lower and upper eyelids were held together for about one second to avoid any loss of test substance. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test substance. Ocular reactions were observed approximately 1, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions and graded according to the Draize method.

 

Very slight to moderate conjunctival reactions (very slight to moderate chemosis, very slight to moderate redness of the conjunctiva and clear discharge) were observed in all animals from day 1; these reactions persisted up to day 11 at the latest. A slight iritis was noted in all animals on day 2; it persisted up to day 4, 5 or 6. A slight corneal opacity was recorded in all animals on day 2; a very slight or slight corneal opacity persisted up to day 4 or 7. Neovascularisation was noted in one animal, from day 6 up to day 9.Mean scores calculated for each animal over 24, 48 and 72 hours were 2.3, 2.7 and 2.3 for chemosis, 3.0, 3.0 and 2.7 for redness of the conjunctiva, 1.0, 1.0 and 1.0 for iris lesions and 2.0, 2.0 and 2.0 for corneal opacity.

 

Under the test conditions, the test material is classified as "Category 2 irritating to eyes" according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP) to the GHS.