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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:
18 April - 03 May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 405 with minor deviation: temperature in the animal room was outside the range
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temperature in the animal room was outside the range
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): PI2080
- Physical state: Limpid amber highly viscous liquid
- Analytical purity: 97 ± 3 %
- Lot/batch No.: 11GP0077
- Date of receipt: 10 February 2012
- Expiration date of the lot/batch: January 2014
- Storage condition of test material: Stored at room temperature and protected from light
- pH of the test item: 6-7 (measured at 25 °C diluted at 1.15 % in isopropanol)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Argenvilliers, France.
- Age at study initiation: 2-4 months
- Weight at study initiation: Mean body weight - 3090 g (2985-3195 g)
- Housing: Animals were individually housed in noryl cages (Tecniplast, 65.3 cm x 65.3 cm x 45 cm).
- Diet: Pelleted breeding diet "type 110C" (SAFE, Augy, France), ad libitum
- Water: Tap water (filtered using a 0.22 μm filter), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 50 ± 20 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- To reduce the viscosity of the dosage formulation and permit its administration with syringes, the formulations were kept in a water bath at 37 °C.
Duration of treatment / exposure:
After one hour, both eyes were rinsed with a sterile isotonic saline solution (0.9% NaCl), under a volume and velocity of flow which did not cause injury to the eyes.
Observation period (in vivo):
Eyes were examined approximately 1, 24, 48 and 72 h after administration of the test item. Since all animals showed persistent ocular reactions at the 72 h reading, the evaluation of ocular reactions was extended up to the complete reversibility (at the latest Day 16).
Number of animals or in vitro replicates:
2 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Both eyes were rinsed with a sterile isotonic saline solution (0.9% NaCl), under a volume and velocity of flow which did not cause injury to the eyes.

SCORING SYSTEM: According to OECD Guideline 405

TOOL USED TO ASSESS SCORE:
- At 24 h after treatment, 0.5 % sodium fluorescein solution was instilled into the eyes and they were examined under UV-lamp to detect the presence of corneal opacification.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 16 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 12 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 9 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
First animal (Y30156):
- Severe chemosis (grade 3) was observed at the 1 h and 24 h observations. Then severity decreased to grade 2 from Days 3 to 9. It decreased to grade 1 from Days 10 to 11 and disappeared on Day 12. A severe redness of the conjunctiva (grade 3) was observed 1 h after treatment, then redness became moderate (grade 2) from Days 2 to 3, slight (grade 1) from Days 4 to 15, and disappeared on Day 16.
Second animal (Y30157):
- Moderate chemosis (grade 2) was observed at the 1 h observation and on Days 2, 3 and 4. Then, severity decreased to grade 1 (slight) on Days 5 and 6 and disappeared on Day 7. A moderate redness of the conjunctiva (grade 2) was observed 1 h after treatment and on Day 2, then severity decreased to grade 1 from Days 3 to 8 and disappeared on Day 9.
Other effects:
- No mortality was observed.
- Moderate or marked alopecia was observed in the first and the second animal from Day 2 to the end of the observation period. Lacrimation was observed on Days 4 and 5 in the first animal and on Days 1 and 2 in the second animal.
- Body weight of the animals was unaffected by the test item treatment.

Any other information on results incl. tables

Table 7.3.2/1: Scores for ocular lesions

Rabbit

No.

Eye lesions

 

Scores

D1

(1 h)

D2

(24 h)

D3

(48 h)

D4 (72 h)

Mean (24, 48 and 72 h)

D5

D6

D7

D8

D9

D10

D11

D12

D13

D14

D15

D 16

Y30156

Conjunctiva: chemosis

3

3

2

2

2.3

2

2

2

2

2

1

1

0

0

0

0

0

Conjunctiva: redness

3

2

2

1

1.7

1

1

1

1

1

1

1

1

1

1

1

0

Iris lesions

0

0

0

0

0.0

0

0

0

0

0

0

0

0

0

0

0

0

Cornea: Opacity intensity

0

0

0

0

0.0

0

0

0

0

0

0

0

0

0

0

0

0

Cornea: Opacity area

0

0

0

0

0.0

0

0

0

0

0

0

0

0

0

0

0

0

Y30157

Conjunctiva: chemosis

2

2

2

2

2.0

1

1

0

0

0

-

-

-

-

-

-

-

Conjunctiva: redness

2

2

1

1

1.3

1

1

1

1

0

-

-

-

-

-

-

-

Iris lesions

0

0

0

0

0.0

0

0

0

0

0

-

-

-

-

-

-

-

Cornea: Opacity intensity

0

0

0

0

0.0

0

0

0

0

0

-

-

-

-

-

-

-

Cornea: Opacity area

0

0

0

0

0.0

0

0

0

0

0

-

-

-

-

-

-

-

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, test item, PI2080 is classified as “R36 irritating to eyes” according to the criteria of Annex VI to the Directive 67/548/EEC and Category 2 with the hazard statement "H319: Causes serious eye irritation" according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 2 healthy male rabbits of the New Zealand White strain were exposed to 0.1 g of test item, PI2080 in their left eye while the right eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test item. At 24 h after treatment, 0.5 % sodium fluorescein solution was instilled into the eyes and they were examined under UV-lamp to detect possible corneal damage. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and Days 5 to 16 after treatment and graded according to the method of OECD Guideline 405.

No mortality was observed. Body weight of the animals was unaffected by the test item treatment. In the first animal, severe chemosis (grade 3) was observed at the 1 h and 24 h observations, then severity decreased to grade 2 from Days 3 to 9 and further decreased to grade 1 from Days 10 to 11 and disappeared on Day 12. A severe redness of the conjunctiva (grade 3) was observed 1 h after treatment, then redness became moderate (grade 2) from Days 2 to 3, slight (grade 1) from Days 4 to 15, and disappeared on Day 16. In second animal, moderate chemosis (grade 2) was observed at the 1 h observation and on Days 2, 3 and 4. Then, severity decreased to grade 1 (slight) on Days 5 and 6 and disappeared on Day 7. A moderate redness of the conjunctiva (grade 2) was observed 1 h after treatment and on Day 2, then severity decreased to grade 1 from Days 3 to 8 and disappeared on Day 9. Both males showed lacrimation on Days 4 and 5 and on Days 1 and 2, respectively. A moderate to marked alopecia was noted around the left eye from Day 2 in both animals. Mean individual scores at 24, 48 and 72 h after exposure for the 2 animals were 0.0, 0.0 for cornea score; 0.0, 0.0 for iris score; 1.7, 1.3 for conjunctivae score and 2.3, 2.0 for chemosis score. In this study, test item, PI2080 is an eye irritant on male rabbits.

 

Under the test conditions, test item, PI2080 is classified as “R36 irritating to eyes” according to the criteria of Annex VI to the Directive 67/548/EEC and Category 2 with the hazard statement "H319: Causes serious eye irritation" according to the CLP Regulation (EC) N° (1272-2008).