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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 24 November 2011 and 08 December 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted 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.

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
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: Diurea thickener 8
Description : light brown solid
Batch number : not supplied
Purity : not supplied
Date received : 12 September 2011
Expiry date : not supplied
Storage conditions: room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.45 to 2.75 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930 Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
0.1 ml of the test item, which was found to weigh approximately 75 mg
Duration of treatment / exposure:
Up to 1 hour
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. )
Details on study design:
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, which was found to weigh approximately 75 mg (as measured by gently compacting the required volume into an adapted syringe) 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.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
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:
animal: 71360 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal: 71413 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks:
No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal: 71414 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 71360 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal: 7413 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal: 7414 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
other: redness
Basis:
animal: 71360 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
other: redness
Basis:
animal: 7413 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
other: redness
Basis:
animal: 7414 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 71360 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal: 71413 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 71414 Male
Time point:
other: Highest score at 1, 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 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.
Minimal conjunctival irritation was noted in all treated eyes one and 24 hours after treatment. Minimal conjunctival discharge persisted in one treated eye at the 48 Hour observation.
Two treated eyes appeared normal at the 48 Hour observation and one treated eye appeared normal at the 72 Hour observation
Other effects:
Bodyweight
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

 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 cornea involved). For each tissue the score was calculated as follows:

Score for conjunctivae        =         (A + B + C) x 2
Score for iris                         =         D x 5
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 (1962), J. Soc. Cosmet. Chem.13, 281‑289 (see Appendix 3) was used to classify the ocular irritancy potential of the test item. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test item.

If evidence of irreversible ocular damage is noted, the test item will be classified as corrosive to the eye.

Table 1              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex

71360Male

71413Male

71414Male

IPR= 2

IPR = 2

IPR = 2

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

1

1

0

0

1

1

0

0

1

1

0

0

B = Chemosis

1

1

0

0

1

0

0

0

1

0

0

0

C = Discharge

0

1

1

0

1

0

0

0

1

0

0

0

Score (A + B + C) x 2

4

6

2

0

6

2

0

0

6

2

0

0

Total Score

4

6

2

0

6

2

0

0

6

2

0

0

 

IPR=  Initial pain reaction

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

71360Male

4

6

2

0

71413Male

6

2

0

0

71414Male

6

2

0

0

Group Total

16

10

2

0

Group Mean Score

5.3

3.3

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

71360Male

2.45

2.53

0.08

71413Male

2.75

2.82

0.07

71414Male

2.53

2.59

0.06

Applicant's summary and conclusion

Interpretation of results:
other: mild irritant
Remarks:
Criteria used for interpretation of results: other: modified Kay and Calandra classification system
Conclusions:
The test item produced a maximum group mean score of 5.3 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 did 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 tobe compatible with thefollowing:

OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted24 April 2002)

Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

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

Conclusion. The test item produced a maximum group mean score of 5.3 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 did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.