Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed GLP and OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
84/449/EEC
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG breeding colony
- Weight at study initiation: 3.1 kg to 3.6 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
24 hours
rinsing with physiolog. saline 24 h post instillation
Observation period (in vivo):
14 days post instillation
Number of animals or in vitro replicates:
3
Details on study design:
Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
1.4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal: # 1, 2, 3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The conjuntciva of all animals were diffuse crimson red coloured and swollen about 1 h until 7 d after application. Hyperemia and clouding of iris and diffuse corneal opacity was observed during the same period. Signs of irritation were not fully reversible after 72 h. Therefore additional assessments were performed after 7 and 14 days.
Other effects:
Clear and white eye discharge was observed at 1 hour until 72 h after application. The conjunctiva of all animals was glassy 1 h after application. One animal showed alopecia in the eye region.

Any other information on results incl. tables

Table 1: individual scores:

Animal no

Evaluation Interval

Cornea

Fluoresceine Test

Conjunctiva

Iris

Alopecia

eye region

 

 

Opacity

 

Redness

Chemosis

Discharge

 

 

1

1 h

1

 

2

2

X

1

 

2

1

 

1

2

X

1

 

3

1

 

1

2

X

1

 

1

24 h

2

4

2

2

X

1

 

2

2

3

2

2

X

1

 

3

1

3

2

2

X

1

 

1

48 h

2

 

2

2

X

1

 

2

2

 

2

2

X

1

 

3

1

 

2

2

X

1

 

1

72 h

1

0

2

1

X

1

 

2

1

1

2

1

 

1

 

3

1

0

2

1

X

1

 

1

7 d

0

 

0

0

 

0

 

2

0

 

0

0

 

0

 

3

1

 

2

1

 

1

X

1

14 d

0

 

0

0

 

0

 

2

0

 

0

0

 

0

 

3

0

 

0

0

 

0

X

Applicant's summary and conclusion

Interpretation of results:
other: Irritating to eyes, category 2
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
Directive 67/548/EEC: irritating to eyes, R 36
(EC) No 1272/2008: Irritating to eyes, category 2

In a OECD guideline and GLP compliant primary eye irritation test in rabbits, the test item caused grade 2 (mean of 24, 48 and 72 h, three animals) conjunctival redness. Thus, the test item has to be classified as "Irritating to eyes, category 2" according to (EC) No 1272/2008 and has not to be classified according to Directive 67/548/EEC (mean score conjunctival redness < 2.5).
The mean scores for corneal opacity (0.7), iris (0.6) and conjunctival chemosis (1.2) did not meet the classification criteria for "Irritating to eyes" according to (EC) No 1272/2008 and Directive 67/548/EEC.
Executive summary:

A study with the test item according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the rabbit eye.

The conjuntciva of all animals were diffuse crimson red coloured and swollen about 1 h until 7 d after application. Hyperemia and clouding of iris and diffuse corneal opacity was observed during the same period. Clear and white eye discharge was observed at 1 hour until 72 h after application. The conjunctiva of all animals was glassy 1 h after application. One animal showed alopecia in the eye region.Signs of irritation were not fully reversible after 72 h. Therefore additional assessments were performed after 7 and 14 days. All signs of irritation were fully reversible after 14 days.

The test item caused grade 1 (mean of 24, 48 and 72 h, three animals) iritis. Thus, the test item has to be classified as "Irritating to eyes, category 2" according to (EC) No 1272/2008 and "irritating to eyes", R 36 according to Directive 67/548/EEC.