Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 405)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Details on test material:

- Physical apprearance: Light yellow viscous liquid
- Batch: 99/484
- Storage: RT in the dark
- Stability undert storage conditions: not indicated
- Specific gravity: 1.23
- Purity: 99% (HPLC)
- Stability under storage conditions: 10th June 2005 (allocated by NOTOX, 1 year after receipt of the test substance)

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: 7- 9 weeks
- Sex: male
- Weight at study initiation: > 1.3 kg
- Housing: individually
- Diet : Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Al tromin, Lage, Germany) approx. 100 g per day. In addition, hay (BMI, Helmond, the Netherlands) was provided at least three times a week .
- Water: Free access to tap-water
- Acclimation period: =>5 days. A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special a ttention was paid to the eyes, which were free from any abnormalit.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2-22.3
- Humidity (%): 33-59
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: other eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
24
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after Instillation of the test substance.
Number of animals or in vitro replicates:
3
Details on study design:
The study was designed as such that, first a single rabbit (sentinel) was treated. The two other animals were treated in a similar manner 5 days later, after considering the degree of skin irritation observed in the first animal.

Each animal was treated by instillation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water containing 2% fluorescein adjusted to pH7
- Time after start of exposure: 24

SCORING SYSTEM: Draize scoring

OBSERVATION
- Mortality: twice daily
- Toxicity: at least once daily
- Body weight measurements: day of treatment (prior to appliation) and the termination

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
for all 3 animals
Time point:
other: 24 + 48 +72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
for all 3 animals
Time point:
other: 24 + 48+ 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: 24 + 48 + 72 h
Score:
0.5
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: 24 + 48 + 72 h
Score:
0.1
Max. score:
4
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual and Mean Value Irritation scores

Readings

Animal

Cornea

Opacity

Iris

 

Conjunctiva

Redness

 

Swelling

1h

1

0

1

1

2

 

2

0

1

2

1

 

3

0

0

2

2

24h

1

0

0

1

0

 

2

0

0

2

0

 

3

0

0

1

1

48h

1

0

0

0

0

 

2

0

0

1

0

 

3

0

0

0

0

72h

1

0

0

0

0

 

2

0

0

0

0

 

3

0

0

0

0

Mean (24h-72h)

1

0,0

0,0

0,3

0,0

 

 2

0,0

0,0

1,0

0,0

 

3

0,0

0,0

0,3

0,3

Mean (24h-72h)

all animals

0,0

0,0

0,6

0,1

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU