[No public or meaningful name is available]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Starting Date: 09 June 2014; Experimental Completion Date: 26 June 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT 65088/A TE
Batch: CUF 176, 3011 SCE 346
Purity: 93.8% w/w
Physical state / Appearance: light yellow powder
Expiry date: 29 September 2017
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:

Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd. At the start of the study the animals weighed 2.53 or 3.29 kg and were twelve to twenty weeks old. After an acclimatization 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 (2930C Teklad Global Rabbit diet) was allowed throughout the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. 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.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A volume of 0.1 mL of the test item, which was found to weigh approximately 93 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.

Duration of treatment / exposure:

Single application with observation to 72 hours.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment

Number of animals or in vitro replicates:

2

Details on study design:

MEASUREMENT OF pH:
The pH of the test material was determined prior to commencement of the study and found to be as follows:
10% w/w aqueous preparation of the test material: pH 8.66 immediately, pH 8.65 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 subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.

A volume of 0.1 mL of the test item, which was found to weigh approximately 93 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 a six point scale.

Eight hours after test item application, a subcutaneous injection of post dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.

After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated.

SCORING:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation: Draize Scale for Scoring Ocular Irritation

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 body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(74366 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects noted

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(74391 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects noted

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(74366 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(74391 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No iridial inflammation noted

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(74366 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(74391 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(74366 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(74391 Male)

Time point:

other: Mean of scores at 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.

No corneal effects were noted during the study.

Iridial inflammation was noted in one treated eye 1 hour after treatment.

Moderate conjunctival irritation was noted in both treated eyes 1 hour after treatment. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 24 Hour observation. Minimal conjunctival irritation was noted in both treated eyes at the 48 Hour observation.

Both treated eyes appeared normal at the 72 Hour observation.

Other effects:

Individual body weights and body weight change are given in Table 3.

Both animals showed expected gain in body weight 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	74366 Male				74391 Male
	IPR= 0				IPR = 0
Time After Treatment	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
F = Area of Cornea Involved	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0
IRIS
D	1	0	0	0	0	0	0	0
Score (D x 5)	5	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	1	0	2	2	1	0
B = Chemosis	2	1	0	0	2	1	0	0
C = Discharge	1	1	0	0	2	1	0	0
Score (A + B + C) x 2	10	6	2	0	12	8	2	0
Total Score	15	6	2	0	12	8	2	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
74366 Male	15	6	2	0
74391 Male	12	8	2	0
Group Total	27	14	4	0
Group Mean Score	13.5	7.0	2.0	0.0

Table 3     Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
	Day 0	Day 3
74366 Male	3.29	3.35	0.06
74391 Male	2.53	2.59	0.06

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 13.5 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 Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

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.

Results

A single application of the test item to the non-irrigated eye of two rabbits produced iridial inflammation and moderate conjunctival irritation. Both treated eyes appeared normal at the 72‑Hour observation.

Conclusion

The test item produced a maximum group mean score of13.5and was classified as amildirritant (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 Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.