C-M5

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 April 2007 and 19 April 2007

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 no effect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: New Zealand White rabbits were supplied by an accredited supplier.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: Weight range of 2.0 to 3.5 kg.
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Certified Rabbit Diet.
- Water (e.g. ad libitum): Free access to mains drinking water and food (Certified Rabbit Diet) was allowed throughout the study.
- Acclimation period: Five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): The 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:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A volume of 0.1 ml of the test material, which was found to weigh approximately 66 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.
- Concentration (if solution): Not available


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution):Not applicable
- Lot/batch no. (if required): Not applicable
- Purity:Not applicable

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable



SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.
Any other ocular effects were also noted
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



TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Remarks:

animal 66163

Time point:

other: mean of 24, 48 and 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Remarks:

animal 66172

Time point:

other: mean of 24, 48 and 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Remarks:

animal 66173

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal 66163

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal 66172

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal 66173

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal 66163

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: No effect noted

Results 8

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal 66172

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: No effect noted

Results 9

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal 66173

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: No effect noted

Results 10

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal 66163

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: no effect noted

Results 11

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal 66172

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: no effect noted

Results 12

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal 66173

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

other: no effect noted

Irritant / corrosive response data:

No corneal or iridial effects were noted.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24-hour observation.
All treated eyes appeared normal at the 48-hour observation.

Other effects:

Purple/pink-coloured staining of the fur was noted around all treated eyes throughout the study.

Any other information on results incl. tables

Individual scores for ocular irritation are given in Table1.

Table1               IndividualScores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex	66163 Male				66172 Male				66173 Male
	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
CONJUNCTIVAE
A = Redness	2	1	0	0	2	1	0	0	2	1	0	0
B = Chemosis	1	1	0	0	1	1	0	0	1	1	0	0
C = Discharge	2Sf	1Sf	0Sf	0Sf	1Sf	1Sf	0Sf	0Sf	1Sf	0Sf	0Sf	0Sf
Score (A + B + C) x 2	10	6	0	0	8	6	0	0	8	4	0	0
Total Score	10	6	0	0	8	6	0	0	8	4	0	0

IPR= Initial pain reaction

Sf= Purple/pink-coloured staining of the fur around the treated eye

The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC (based on the mean scores for each animal).

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

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

§        Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004/73/EC

A single application of the test material was applied to the non-irrigated eye of three rabbits. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

No corneal or iridial effects were noted.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted in all treated eyes at the 24-hour observation.

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

The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC.