Registration Dossier

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: FHSA
Principles of method if other than guideline:
Test substance administered to the eye of 6 rabbits. Treated eyes of 3 rabbits washed after 30 seconds. Reaction assessed after 1, 24, 48 and 72 hours, 6, 10 and 14 days
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
- Name of test material (as cited in study report):TK 10 946

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: In-house breeding
- Age at study initiation: 12 - 15 weeks
- Weight at study initiation: 2.5 - 2.7 kg
- Housing: Individually caged
- Diet (e.g. ad libitum): Styles-Oxoid commercial rabbit diet, ad libitum
- Water (e.g. ad libitum): Sterile filtered water, ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 deg C
- Humidity (%): 50 - 70%
- Photoperiod (hrs dark / hrs light): 10 hours light / 14 hours dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
Single administration. The eyes of 3 animals washed 30 seconds after administration
Observation period (in vivo):
1, 24, 48 and 72 hours, 6, 10 and 14 days
Number of animals or in vitro replicates:
6, 3 unwashed and 3 washed
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, 3 rabbits, 200 mL warm water
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: fluorescein staining to aid visualisation of corneal lesions

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 6 days

Any other information on results incl. tables

 

 

Unwashed

 

 

Animal Number: 11

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

2

 

3

 

3

 

2

 

 

 

Conjunctivae:

Chemosis:

2

2

2

2

4

 

 

 

Redness:

2

3

3

3

2

 

 

 

Iris:

 

Inflammation:

 

0

 

1

 

1

 

1

 

1

 

 

 

 

 

Cornea:

 

Opacity:

 

2

 

1

 

1

 

1

 

2

 

 

 

 

Area:

4

4

4

4

4

 

 

 

 


 

 

Unwashed

 

 

Animal Number: 13

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

3

 

3

 

3

 

3

 

2

 

 

 

Conjunctivae:

Chemosis:

2

3

3

3

3

 

 

 

Redness:

2

3

3

3

3

 

 

 

Iris:

 

Inflammation:

 

0

 

1

 

1

 

1

 

1

 

 

 

 

 

Cornea:

 

Opacity:

 

2

 

1

 

1

 

1

 

2

 

 

 

 

Area:

4

4

4

4

3

 

 

 

 


 

 

Unwashed

 

 

Animal Number: 12

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

3

 

3

 

3

 

3

 

 

 

Conjunctivae:

Chemosis:

3

3

2

2

3

 

 

 

Redness:

2

3

3

3

3

 

 

 

Iris:

 

Inflammation:

 

0

 

1

 

1

 

1

 

1

 

 

 

 

 

Cornea:

 

Opacity:

 

2

 

1

 

1

 

2

 

2

 

 

 

 

Area:

4

4

4

3

3

 

 

 

 


 

 

Washed

 

 

Animal Number: 15

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

2

 

2

 

1

 

0

 

0

 

0

Conjunctivae:

Chemosis:

2

3

2

2

1

0

0

 

Redness:

2

3

3

3

3

3

1

 

Iris:

 

Inflammation:

 

1

 

1

 

1

 

0

 

0

 

0

 

0

 

 

Cornea:

 

Opacity:

 

1

 

1

 

1

 

1

 

1

 

1

 

1

 

Area:

4

4

4

4

4

2

1

 

 


 

 

Washed

 

 

Animal Number: 14

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

3

 

3

 

2

 

1

 

0

 

1

 

0

Conjunctivae:

Chemosis:

3

3

2

2

1

1

1

 

Redness:

2

3

3

3

3

3

3

 

Iris:

 

Inflammation:

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

Cornea:

 

Opacity:

 

1

 

1

 

1

 

1

 

1

 

1

 

1

 

Area:

4

4

4

3

3

1

1

 


 

 

Washed

 

 

Animal Number: 16

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

3

 

2

 

1

 

0

 

0

 

0

Conjunctivae:

Chemosis:

2

2

2

1

0

0

0

 

Redness:

2

3

3

3

3

3

3

 

Iris:

 

Inflammation:

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

Cornea:

 

Opacity:

 

1

 

1

 

1

 

1

 

1

 

1

 

1

 

Area:

3

4

2

2

2

1

1

 

 

Unwashed

 

 

Animal

Number

Conjunctival

Redness

 

 

Conjunctival

Chemosis

 

Iris

Inflammation

 

Corneal

Opacity

 

11

13

12

3.0

3.0

3.0

2.0

3.0

2.3

1.0

1.0

1.0

1.0

1.0

1.3

 

The mean score recorded for each animal is the average of the individual scores observed at the 24, 48 and 72 hour examinations.

 

 

 

Washed

 

 

Animal

Number

Conjunctival

Redness

 

 

Conjunctival

Chemosis

 

Iris

Inflammation

 

Corneal

Opacity

 

15

14

16

3.0

3.0

3.0

2.3

2.3

1.7

0.7

0.0

0.0

1.0

1.0

1.0

 

The mean score recorded for each animal is the average of the individual scores observed at the 24, 48 and 72 hour examinations.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Primary eye irritation has been investigated in the rabbit. Hexahydrophthalic anhydride causes serious eye damage.
Executive summary:

Acute eye irritation has been investigated in the rabbit following administration of a single dose and following FHSA test methods, which are similar to current OECD test methods. Hexahydrophthalic anhydride causes serious eye damage.