Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 September to 5 November 1999
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Solid
Details on test material:
- Name of test material (as cited in study report): Pymordiol
- Physical state: Cream white solid
- Purity of test material: 96% wt%
- Expiration date of the lot/batch: 1 January 2001
- Stability under test conditions: Stable under test conditions
- Storage condition of test material: At room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: At least 6 weeks of age
- Weight at study initiation: 3.5 kg
- Housing: Individually cages with perforated floors
- Diet: 100 g per day of Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany). Hay was provided once per week (BMI, Helmond, the Netherlands).
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21˚C
- Humidity (%): 50%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/ 12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 54.6 mg +/- 0.4 mg (volume of approx. 0.1 mL)

Duration of treatment / exposure:
24 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 Animals of one sex
Details on study design:
SCORING SYSTEM: See Tables No. 1 - 5 below

TOOL USED TO ASSESS SCORE: Fluorescein, and the use of ophthalmic examination lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 hours
Score:
ca. 0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 hours
Score:
ca. 0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: 24-72 hours
Score:
ca. 0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 hours
Score:
ca. 0
Max. score:
4
Irritant / corrosive response data:
Iridial irritation was reported in all animals on day 1 and was resolved within 24 hours.

Irritation of the conjunctivae was seen as redness, chemosis and discharge, which was completely resolved within 48 hours in one animal and 72 hours in the other test animals.

No corneal opacity was reported.

See tables No. 6 - 7 below for details on individual test animals and mean scores.
Other effects:
No symptoms of systemic toxicity was observed in the animals during the test period and no mortality was observed.

Any other information on results incl. tables

Table 6: Individual Eye Irritation Scores

Animal No. 469 470 471
Time After Dosing Tissue/Finding Score Fluor. Area (%) Comments Score Fluor. Area (%) Comments Score Fluor. Area (%) Comments
1 hour Corneal Opacity 0 Remnants of test substance in the eye 0 Remnants of test substance in the eye 0 Remnants of test substance in the eye
Area 0 0 0
Iris 1 1 1
Conj Redness 1 (ABC) 2 (C) 2(C)
Chemosis 1 (B) 1 (ABC) 2(C)
Discharge 1 1 1
24 hours Corneal Opacity 0 0 0 0
Area 0 0 0
Iris 0 0 0
Conj Redness 1 (ABC) 2 (C) 1 (ABC)
Chemosis 0 0 0
Discharge 0 1 0
48 hours Corneal Opacity 0 0 0
Area 0 0 0
Iris 0 0 0
Conj Redness 0 1(C) 1(C)
Chemosis 0 0 0
Discharge 0 0 0
72 hours Corneal Opacity 0 0 0
Area 0 0 0
Iris 0 0 0
Conj Redness 0 0 0
Chemosis 0 0 0
Discharge 0 0 0

Score given for:

A = Eyelids,

B = Nictitating membrane, and

C = Sclera

Table 7: Mean Values of Eye Irritation Scores (24 -72 h after instillation)

Animal No. Mean 24 - 72 hours
Corneal Opacity Iris Conjunctivae
Redness Chemosis
469 0 0 0.3 0
470 0 0 1 0
471 0 0 0.7 0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under current test conditions test substance is not considered irritating to the eye.