Performance Standards for Applying Human Skin Models to in Vitro Skin Irritation Testing Content

3 INTRODUCTION......................................................................................................................................... 2 3.1 REGULATORY RATIONALE FOR USING IN VITRO TEST METHODS TO ASSESS SKIN IRRITATION ................... 3 3.2 PRINCIPLE OF IN VITRO HUMAN SKIN MODEL SYSTEMS FOR SKIN IRRITATION TESTING............................. 3 4 GENERAL SKIN MODEL PERFORMANCE.............................................................................................. 4 4.1 IN VITRO HUMAN SKIN MODEL CHARACTERISTICS................................................................................... 4 5 TEST ACCEPTANCE CRITERIA............................................................................................................... 5 5.1 TEST SUBSTANCES................................................................................................................................ 5 5.2 CONTROL SUBSTANCES......................................................................................................................... 5 5.2.1 Negative Control (NC)..................................................................................................................... 5 5.2.2 Positive Control (PC)....................................................................................................................... 5 6 TEST PROCEDURE AND DATA INTERPRETATION .............................................................................. 6 6.1 TEST SUBSTANCES................................................................................................................................ 6 6.2 VIABILITY MEASUREMENTS..................................................................................................................... 6 6.3 VIABILITY DATA INTERPRETATION PROCEDURE / PREDICTION MODEL....................................................... 6 6.4 COMPLEMENTARY ENDPOINTS................................................................................................................ 6 6.4.1 Example of Interleukin 1 alpha (IL-1α) measurements in EPISKIN model..................................... 7 6.5 TEST REPORTING .................................................................................................................................. 7 7 REFERENCE CHEMICALS........................................................................................................................ 8 7.1 SELECTION CRITERIA............................................................................................................................. 8 7.2 PROPOSED REFERENCE CHEMICALS ...................................................................................................... 8 8 SPECIFIC TEST PERFORMANCE: RELIABILITY AND PREDICTIVITY............................................... 10 8.1 RELIABILITY......................................................................................................................................... 10 8.1.1 Reproducibility within one laboratory (and over time) ................................................................... 10 8.1.2 Reproducibility between laboratories (and over time)................................................................... 10 8.2 PREDICTIVITY ...................................................................................................................................... 10 9 COMPLEMENTARY ENDPOINT (IL-1α RELEASE) ............................................................................... 11