DEVELOPMENT OF A SHORT TERM IN-VITRO DERMAL TOXICITY SCREENING TEST USING HUMAN CELLS

THERE IS A LARGE EFFORT UNDERWAY IN THE WORLD TODAY TO IDENTIFY AND DEVELOP IN-VITRO ALTERNATIVE TESTS TO SUPPLEMENT OR REPLACE CURRENT IN-VIVO TOXICITY TEST METHODS. THE AGAROSE DIFFUSION METHOD IS AN EXCELLENT CANDIDATE FOR DEVELOPMENT AS A SHORT TERM IN-VITRO DERMAL TOXICITY SCREENING TEST USING HUMAN CELLS. THE PHASE I EFFORT WILL ATTEMPT TO ADAPT THE CURRENT AGAROSE DIFFUSION METHOD FOR USE IN SCREENING FOR PRIMARY SKIN IRRITATION. THIS MAY REQUIRE MANIPULATION OF THE AGAROSE THICKNESS, VARYING THE SERUM CONTENT IN THE CULTURE MEDIUM, AND USING ALTERNATIVE CELL TYPES. APPROPRIATE HUMAN CELL LINES WILL BE ADAPTED TO THE TEST METHOD. OF PRIMARY INTEREST IS THE USE OF A PRIMARY HUMAN FORESKIN CELL LINE. OTHER CELL LINES MAY BE CONSIDERED. OF PARTICULAR INTEREST IS A COMPARISON OF HUMAN CELL LINES WITH THE L-929 MOUSE FIBROBLAST CELL LINE THAT HAS BEEN USED IN THIS TEST METHOD BY THE MEDICAL DEVICE INDUSTRY FOR OVER 20 YEARS. FOLLOWING ADAPTATION OF THE TEST METHOD, PRELIMINARY SCREENING OF KNOWN SAMPLES AND COMPARISON WITH RABBIT DERMAL TOXICITY DATA WILL BE CONDUCTED. NAMSA HAS AVAILABLE A CONSIDERABLE COLLECTION OF DATA GENERATED ON VARIOUS TEST MATERIALS. THIS WILL ALLOW A RAPID EVALUATION OF THE CORRELATION BETWEEN THE AGAROSE DIFFUSION METHOD AND RABBIT DERMAL TOXICITY TESTING.