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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:
The study was performed between 18 July 2011 and 28 July 2011.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)

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:
TEST ANIMALS- Source: Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. - Age at study initiation: twelve to twenty weeks old- Weight at study initiation: At the start of the study the animals weighed 2.56 to 2.90 kg- Housing: The animals were individually housed in suspended cages. - Diet (e.g. ad libitum): Free access to food (2930 Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. - Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study. - Acclimation period: At least five days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 17 to 23°C - Humidity (%): 30 to 70%Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. - Air changes (per hr): At least fifteen changes per hour- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIALA volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye.
Duration of treatment / exposure:
SIngle application for 72 hour exposure.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
MEASUREMENT OF PH:The pH of the test item was determined prior to commencement of the study and found to be as follows:Undiluted as supplied: pH 4.01 (immediately), pH not applicable (after 10 minutes)10% w/w aqueous preparation of test item: pH 4.5 (immediately), pH 4.5 (after 10 minutes) PROCEDURE:Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.Initially, a single rabbit was treated. A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1 (see attached background material).After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. In order to minimise pain on application of the test item, one drop of local anaesthetic (Tetracaine hydrochloride 0.5%, Bausch & Lomb, Surrey, UK) was instilled into both eyes of these animals 1 to 2 minutes before treatment.SCORING SYSTEM:Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical Draize Scale for Scoring Ocular Irritation (see Appendix 2 - attached background material).Any other ocular effects were also noted.TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.Other:Any clinical signs of toxicity, if present, were also recorded.Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 1 - 70698)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 2 - 70741)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 3 - 70742)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 1 - 70698)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 2 - 70741)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 3 - 70742)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1 - 70698)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 2 - 70741)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 3 - 70742)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1 - 70698)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 2 - 70741)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 3 - 70742)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Ocular Reactions:Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.No corneal or iridial effects were noted during the study.Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Minimal conjunctival irritation was noted in all treated eyes at the 24-Hour observation and in one treated eye at the 48-Hour observation.Two treated eyes appeared normal at the 48-Hour observation and the remaining treated eye appeared normal at the 72-Hour observation
Other effects:
Individual bodyweights and bodyweight changes are given in Table 3.All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

70698 Male

70741 Male

70742 Male

IPR= 3

IPR = 0+

IPR = 0+

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

1
Hour

24
Hours

48
Hours

72
Hours

1
Hour

24
Hours

48
Hours

72
Hours

CORNEA

 

 

 

 

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

0

0

0

0

F = Area of Cornea Involved

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

2

1

1

0

2

1

0

0

2

1

0

0

B = Chemosis

2

1

0

0

2

1

0

0

2

1

0

0

C = Discharge

2

1

0

0

2

1

0

0

2

1

0

0

Score (A + B + C) x 2

12

6

2

0

12

6

0

0

12

6

0

0

Total Score

12

6

2

0

12

6

0

0

12

6

0

0


IPR=  Initial pain reaction

+=     One drop of local anaesthetic instilled into both eyes 1 to 2 minutes before treatment

Table 2              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

70698 Male

12

6

2

0

70741 Male

12

6

0

0

70742 Male

12

6

0

0

Group Total

36

18

2

0

Group Mean Score

12.0

6.0

0.7

0.0

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

70698 Male

2.84

2.89

0.05

70741 Male

2.56

2.59

0.03

70742 Male

2.90

2.96

0.06

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Two treated eyes appeared normal at the 48-Hour observation and the remaining treated eye appeared normal at the 72-Hour observation.The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.
Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.2400 Acute Eye Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

Result.

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Two treated eyes appeared normal at the 48-Hour observation and the remaining treated eye appeared normal at the 72-Hour observation.

Conclusion.

The test item produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.