[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:

05 February 2013 to 26 February 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with GLP and agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Justification for type of information:

See Read-Across Justification in Section 13.

Cross-reference

Reason / purpose for cross-reference:

other: Target record

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 for cross-reference:

read-across source

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: Mean of 24, 48 and 72 hour observations

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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

Test material information

Constituent 1

Reference substance name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl) -L-glutamate and sodium hydrogen n-(1-oxohexadecyl) -L-glutamate

IUPAC Name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl) -L-glutamate and sodium hydrogen n-(1-oxohexadecyl) -L-glutamate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Appearance: White to pale yellow powder
- Storage conditions of test material: Room temperature (15-25 °C)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 3491 and 3551 g
- Housing: Individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbits in adjoining cages
- Diet: ad libitum
- Water: municipal tap water ad libitum
- Acclimation period: 27 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16.8 to 20.2 °C
- Humidity: 24 to 68 % (relative)
- Air changes: 15 to 20 changes per hour
- Photoperiod: 12 hour light/dark cycle (light from 06:00 to 18:00)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated contralateral eye served as the control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- pH: The pH of the test material was determined prior to dosing. The test material was found to be acceptable for use in the test (pH 5)

- TOPICAL ANAESTHETIC AND SYSTEMIC ANALGESIC
- Schedule: Sixty minutes (60 ± 10 minutes) prior to administration, a systemic opiate analgesic (Buprenorphine 0.01 mg/kg) was administered by subcutaneous injection. Five minutes (5 ± 1.5 minutes) prior to administration, a topical ocular anaesthetic (Humacain (oxybuprocaine) one-two drops per eye) was applied to each eye (including the control eye to ensure direct comparison of any ocular observations). Eight hours (8 to 9 hours) after test material application, Buprenorphine 0.01 mg/kg and a nonsteroidal anti-inflammatory drug (NSAID) (Meloxicam 0.5 mg/kg) were administered by subcutaneous injection. The systemic opiate analgesic was injected approximately every 12 hours and the NSAID every approximately every 24 hours until the ocular lesions were resolved and no clinical signs of pain or distress were present.

Duration of treatment / exposure:

A single dose was administered

Observation period (in vivo):

3 weeks (21 days)

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline
- Time after start of exposure: At the 1 and 24 hour observation point in one animal and at the 1 hour observation point only in the second animal.

SCORING SYSTEM: Draize (1977) and OECD 405.
The eyes were examined at in the first animal 1, 24, 48 and 72 hours, then 1, 2 and 3 weeks after treatment. The eyes were examined in the second animal 1, 24, 48 and 72 hours, then 1 and 2 weeks after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 9

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 10

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritant / corrosive response data:

For the irritant response of each animal, the mean score of the 24, 48 and 72 hour observations were calculated for each effect observed.

Other effects:

There was no mortality during the test. One animal showed slight bodyweight loss during the treatment period. The second rabbit was found to be within the normal range. There were no clinical signs observed that could be related to treatment.
No initial pain reaction was observed in either animal.

Any other information on results incl. tables

Table 1: Results for Animal No. 01973

Time	Irritation Score							IPR/ PR
	Conjunctivae			Cornea		Iris	Control eye
	R	CH	D	OD	OE
0 hours*	0	0	0	0	0	0	0	0
1 hour	2	2	3	0	0	0	0	0
24 hours	2	2	3	1	3	0	0	0
48 hours	1	1	3	1	3	0	0	0
72 hours	1	1	2	1	3	0	0	0
7 days	1	1	1	1	3	0	0	0
14 days	1	1	1	1	3	0	0	0
21 days	0	0	0	0	0	0	0	0

* Pre-treatment

IPR/PR - Initial Pain Reaction/Pain Response

R – Redness

CH- Chemosis

D – Discharge

OD –Opacity (degree of density)

OE – Area of opacity

Table 2: Results for Animal No. 01950

Time	Irritation Score							IPR/PR
	Conjunctivae			Cornea		Iris	Control eye
	R	CH	D	OD	OE
0 hours*	0	0	0	0	0	0	0	0
1 hour	2	2	3	1	4	0	0	0
24 hours	2	1	2	1	4	0	0	0
48 hours	2	1	1	1	3	0	0	0
72 hours	2	1	1	1	3	0	0	0
7 days	1	0	1	0	0	0	0	0
14 days	0	0	0	0	0	0	0	0

* Pre-treatment

IPR/PR - Initial Pain Reaction/Pain Response

R – Redness

CH- Chemosis

D – Discharge

OD –Opacity (degree of density)

OE – Area of opacity

Table 3: Results of Bodyweight Observations

Time point	Bodyweight (g)	Bodyweight gain (g)
Animal no. 01973
Prior to treatment	3491	325
21 February 2013 (16 days)	3752
Termination of the study	3816
Animal no. 01950
Before treatment	3551	-1
Before euthanasia	3550

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the test material caused eye irritation in two New Zealand White rabbits. The effects were found to be reversible within 21 days.

Executive summary:

The eye irritation potential of the test material was investigated in New Zealand White rabbits in a study conducted in accordance with the standardised guideline OECD 405 under GLP conditions.

Two animals were exposed to the test material. 0.1 g of the test material was instilled into the conjunctival sac of the eye of each rabbit. The eyes were rinsed at the 1 and 24 hour examination points with physiological saline in one animal, and at the 1 hour observation point only in the second animal. Prior to dosing and during the observation period, a pain management regimen was administered (topical anaesthetic and systemic analgesic) which was continued until all eye effects had resolved. The animals were observed for up to 21 days, and any effects noted were evaluated in accordance with the Draize Scale (1977).

The animal individual mean scores (considering readings taken at 24, 48 and 72 hours after the treatment) were as follows:

Chemosis: 1.33 and 1.00

Discharge: 2.67 and 1.33

Redness: 1.33 and 2.00

Corneal opacity: 1.00 and 1.00

Iris: 0.00 and 0.00

There were no observed pain reactions related to the test material. One animal was reported to have a reduced bodyweight during the study.

Under the conditions of the study, the test material caused eye irritation in two New Zealand White rabbits. The effects were found to be reversible within 21 days.