Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 August 2009 - 21 January 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges
GLP compliance:
yes (incl. QA statement)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: brown black liquid
- Lot/batch No.: prélévement SR320 du 1 juillet 2009
- Expiration date of the lot/batch: 01/07/2011
- Storage condition of test material: at room temperature
- Purity/Impurities: not applicable (complex composition)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Grimaud Frères Sélection S.A.S.
- Age at study initiation: 2 to 4 months
- Weight at study initiation: 3.094 ± 0.054 kg
- Housing: Pajon cages (50 cm x 57 cm x 75 cm)
- Diet (e.g. ad libitum): 112C pelleted diet
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 27 August 2009 To: 06 September 2009

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye, which remained untreated, served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL.
Duration of treatment / exposure:
Single application to the eye
Observation period (in vivo):
6 days.
Number of animals or in vitro replicates:
Three males.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: UV lamp and 0.5% of sodium fluorescein solution.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: mean irritation score
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: mean irritation score
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: mean irritation score
Irritation parameter:
cornea opacity score
Remarks:
corneal opacity (intensity)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable - no reaction
Remarks on result:
other: mean irritation score
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: mean irritation score
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: mean irritation score
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: mean irritation score
Irritation parameter:
cornea opacity score
Remarks:
corneal opacity (intensity)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable - no reaction
Remarks on result:
other: mean irritation score
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: mean irritation score
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: mean irritation score
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable - no reaction
Remarks on result:
other: mean irritation score
Irritation parameter:
cornea opacity score
Remarks:
corneal opacity (intensity)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable - no reaction
Remarks on result:
other: mean irritation score
Irritant / corrosive response data:
A slight or moderate chemosis (grade 1 or 2) was noted in all animals from day 1 until day 3 (animal Nos. 935 and 938/973) or 5 (animal No. 937). A slight or moderate redness of the conjunctiva (grade 1 or 2) was observed in all animals from day 1 until day 4 (animal Nos. 935 and 938/973) or 5 (animal No. 937).
Iris lesions (grade 1) were noted in 2/3 animals (Nos. 935 and 937) on day 2.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 2.0 and 1.0 for chemosis, 1.7, 2.0 and 1.3 for redness of the conjunctiva, 0.3, 0.3 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.
Other effects:
A clear to whitish purulent discharge was observed in all animals on days 2 and 3.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information
Conclusions:
Under the experimental conditions of the study, the test item was slightly irritant when administered by ocular route to rabbits.
Executive summary:

The potential of the test item to induce ocular irritation was evaluated following a single topical applications to rabbits according to OECD (No. 405, 24th April 2002) and Council Regulation (EC) (No. 440/2008, B.5, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. The test item was first administered to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then evaluated simultaneously in two other animals. A single dose of 0.1 mL of the undiluted test item was instilled into the left conjunctival sac. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. A slight or moderate chemosis was noted in all animals from day 1 until day 3 (2/3 animals) or 5 (1/3 animals). A slight or moderate redness of the conjunctiva was observed in all animals from day 1 until day 4 (2/3 animals) or 5 (1/3 animals). A clear to whitish purulent discharge was observed in all animals on days 2 and 3. Iris lesions were noted in 2/3 animals on day 2. Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 2.0 and 1.0 for chemosis, 1.7, 2.0 and 1.3 for redness of the conjunctiva, 0.3, 0.3 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. Under these experimental conditions, the test item was slightly irritant when administered by ocular route to rabbits.