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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
Study period:
13 March 1989 - 17 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across to similar substance. Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Justification for type of information:
See read-across justification in Section 13.
Cross-reference
Reason / purpose:
other: Target substance
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read across material
Justification for type of information:
See read-across justification in Section 13.
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0.34
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: Not applicable

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Description: White powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K
- Age at study initiation: 12 – 16 weeks
- Weight at study initiation: 2.59 – 2.94kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet (e.g. ad libitum): ad libitum. Free access to food (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 14 - 18°C
- Humidity (%):60 - 65% relative
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): give 12 hours continuous light and 12 hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
The test material (100 mg) was placed into the right eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test material was dropped. The upper and lower eyelids were held
together for about one second immediately after application, to prevent loss of the test material, and then released.
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
For the purpose of this study the test material was used as supplied.
The identification and stability of the test material were not determined.

Procedure
Immediately before commencement of the test, both eyes of the three provisionally selected test rabbits were examined for evidence of ocular irritation or defect using the light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.

On the day of the test each animal was held firmly but gently until quiet. The test material (100 mg) was placed into the right eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test material was dropped. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes.

The initial pain reaction was assessed for each animal, immediately after dosing, according to a six point scale.
Assessment of damage/irritation was made 1, 24, 48 and 72 hours following treatment, according to the numerical evaluation developed by Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"). Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

No evidence of ocular irritation was noted at the 72-hour observation and the study was terminated.

Interpretation of Results
The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of opacity). For each tissue the total score was calculated as follows:

Total score for conjunctivae = (A + B + C) x 2
Total score for iris = D x 5
Total score for cornea = (E x F) x 5

Using the numerical data obtained a modified version of the system described by Kay J.H. and Calandra J.C., J. Soc. Cosmet. Chem., 1962 13 281 - 289 was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the total scores for the cornea, iris and conjunctivae for each of the 1, 24, 48 and 72-hour observations for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0.34
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean overall score for 24, 48 and 72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
mean
Time point:
other: Mean overall score for 24, 48 ad 72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritant / corrosive response data:
Slight to moderate initial pain was noted following treatment. No adverse corneal or iridial effects were noted.

Moderate conjunctival irritation was noted in two treated eyes one hour after treatment. Minimal conjunctival irritation was noted in one treated eye at this time and in all treated eyes at the 24-hour observation.

All treated eyes appeared normal at the 48-hour observation.

Any other information on results incl. tables

 Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

25 Male

(IPR = 2)

102 Female

(IPR = 3)

89 Female

(IPR = 2)

Time After Treatment

1

h

24 h

48 h

72 h

1

h

24 h

48 h

72 h

1

h

24 h

48 h

72 h

CORNEA

E = Degree of opacity

F = area of opacity

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

 

0

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

0

0

0

IRIS

D

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

0

Score (D x 5)

0

0

0

0

0

0

0

0

0

0

0

0

CONJUNCTIVAE

A = Redness

B = Chemosis

C = Discharge

 

2

1

0

 

1

0

0

 

0

0

0

 

0

0

0

 

2

1

1

 

1

1

0

 

0

0

0

 

0

0

0

 

2

1

1

 

1

0

0

 

0

0

0

 

0

0

0

Score (A + B + C) x 2

6

2

0

0

8

4

0

0

8

2

0

0

Total Scores

6

2

0

0

8

4

0

0

8

2

0

0

Key: h = hour(s)

IPR = initial pain reaction        

                                                                                      

Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex

Individual Total Scores at:

1 hour

24 hours

48 hours

72 hours

25 Male

102 Female

89 Female

6

8

8

2

4

2

0

0

0

0

0

0

Group Total

22

8

0

0

Group Mean Scores

 

7.3

 

2.7

 

0.0

 

0.0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a maximum group mean score of 7.3 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra scoring system. However the reactions seen were not sufficient to warrant classification.
Executive summary:

The test material produced a maximum group mean score of 7.3 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra scoring system. However the reactions seen were not sufficient to warrant classification. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as method B5 in Annex V of EEC Commission Directive 84/449/EEC.