## FINAL REPORT

Study Title 

## SCREENING FOR THE EY E IRRITANCY POTENTIA L OF EXP1313100 USING THE BOVINE COR NEAL OPACITY AND

PERMEABILITY TEST (B COP TEST)
Author

Test Facility WIL Research Europe B.V. Hambakenwetering 7 5231 DD ‘s
- Hertogenbosch The Netherlands Laboratory Project Identification Project 505701 Substance 205622 /A

- Page 1 of 17
-EXP1313100 Project 505701

- Page 2 - 1. CONTENTS 1. CONTENTS

...................................................................................................................................... 2 2. STATEMENT OF GLP COMPLIANCE

............................................................................................. 3 3. QUALITY ASSURANCE STATEMENT

............................................................................................ 4 4. SUMMARY

........................................................................................................................................ 5 5. INTRODUCTION

.............................................................................................................................. 6 5.1. Preface

...................................................................................................................................... 6 5.2. Aim of the study

................................................................ ........................................................ 6 5.3. Guidelines

................................................................................................................................ . 6 5.4. Storage and retention of records and materials

................................................................ ........ 7 6. MATERIALS AND METHODS

.......................................................................................................... 7 6.1. Test Substance

......................................................................................................................... 7 6.1.1. Test substance information

............................................................................................. 7 6.1.2. Study specific test substance information

................................................................ ...... 7 6.1.3. Test substance preparation

............................................................................................ 7 6.2. Reference substances

................................................................ .............................................. 7 6.3. Test system

............................................................................................................................... 8 6.4. Study design

............................................................................................................................. 8 6. 4.1. Preparation of corneas

................................................................................................... 8 6.5. Cornea selection and Opacity reading

...................................................................................... 8 6.6. Treatment of corneas and opacity measurements

................................................................ .... 8 6.7. Opacity measurement

................................................................ ............................................... 9 6.8. Application of sodium fluorescein

............................................................................................. 9 6.9. Permeability determinations

...................................................................................................... 9 6.10. Electronic data capture

................................................................ ........................................... 9 6.11. Interpretation

.......................................................................................................................... 9 6.11.1. In vitro irritancy score

................................................................................................... 9 6.11.2. Acceptability of the assay

........................................................................................... 10 6.12. List of deviations

................................................................ ................................................... 10 6.12.1. List of protocol deviations

........................................................................................... 10 6.12.2. List of standard operating procedures deviations

...................................................... 10 7. RESULTS

....................................................................................................................................... 10 8. DISCUSSION AND CONCLUSION

................................................................................................ 11 9. REFERENCES

............................................................................................................................... 12
TABLES Table 1 Summary of opacity, permeability and in vitro scores .................................................. 13 Table 2 Opacity score

................................................................ ................................................ 14 Table 3 Permeability score individual values (uncorrected)

...................................................... 14 Table 4 Permeability score individual values (corrected)

.......................................................... 15 Table 5 In Vitro irritancy score

................................................................................................... 15 Table 6 Historical control data for the BCOP studies

................................................................ 16
APPENDICES APPENDIX 1 SUMMARY TABLE

....................................................................................................... 13 APPENDIX 2 INDIVIDUAL OPACITY, PERMEABILITY AND IN VITRO SCORES

........................... 14 APPENDIX 3 HISTORICAL CONTROL DATA

................................................................................... 16 APPE NDIX 4 CERTIFICATE OF ANALYSIS

...................................................................................... 17EXP1313100 Project 505701

- Page 5 - 4. SUMMARY Screening for the eye irritancy potential of EXP1313100 using the Bovine Corneal Opacity and Permeability test (BCOP test). This report describes the ocular irritation properties of EXP1313100 on an isolated bovine cornea. The possible ocular irritancy of EXP1313100 was tested through topical application for 10 ± 1 minutes. The study procedures described in this report were based on the most recent OECD and EC guidelines. Batch E00873- 025
- 001 of EXP1313100 was a brown solid. The test substance was added as it is via a gauze patch of approximately 2 cm 2 directly on top of the cornea (approximately 400 mg). The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro

irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 126 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. EXP1313100 induced ocular irritation through both endpoints in the category mild to moderate, resulting in a mean in vitro irritancy score of 4.3 after 10 minutes of treatment. Since EXP1313100 induced an IVIS > 3 ≤ 55.1, no prediction on the classification can be made

.