3,4-dihydroxy-1-[(Z)-octadec-9-enyl]pyrrolidine-2,5-dione

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 November 2009 - 04 December 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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

Details on test material:

- Physical state: tan colored solid
- Storage condition of test material: room temperature in the dark

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: Recieved 23 June 2008 from sponsor

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark
- Stability under storage conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final preparation of a solid: Ground to powder prior to testing

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: 12-20 weeks
- Weight at study initiation: 2-3.5kg
- Housing: Individually in suspended cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

~72mg

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hrs

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 13

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24/48/72 h

Score:

12

Reversibility:

fully reversible within: 72 hrs

Irritant / corrosive response data:

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

All treated eyes appeared normal at the 72-hour observation,
The Group Mean Scores according to the Draize scale were 12.0, 10.7, 5.3 and 0.0 out of 110 at I, 24 48 and 72 hours respectively.

Applicant's summary and conclusion

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Conclusions:

The test material produced a maximum group mean score of 12.0 and was classified as a MILD IRRITANT (Class 4 on a I to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. This mateiral is not classifiable as an eye irritant uner the EU DSD or CLP criteria.

Executive summary:

Summary

Introduction

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 24 April 2002)g of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 April 2002)
• Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004/73/EC

Result.

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72-hour observation.

 

The Group Mean Scores according to the Draize scale were 12.0, 10.7, 5.3 and 0.0 out of 110 at 1, 24, 48 and 72 hours respectively.

 

Conclusion.

The test material 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.