The ECVAM international validation study on in vitro tests for acute skin irritation, Report on the validity of the EPISKIN and EpiDerm assays and on the Skin Integrity Function Test

摘要: ECVAM sponsored a formal validation study on three in vitro tests for skin irritation, of which two employ reconstituted human epidermis models (EPISKINtrade mark, EpiDermtrade mark), and one, the integrity function test (SIFT), employs ex vivo mouse skin. The goal was to assess whether would correctly predict classifications according EU classification scheme, "R38" "no label" (i.e. non-irritant). 58 chemicals (25 irritants 33 non-irritants) were tested, having been selected give broad coverage physico-chemical properties, an adequate distribution irritancy scores derived from rabbit irritation tests. In Phase 1, 20 these (9 11 tested with coded identities by single lead laboratory each methods, confirm suitability protocol improvements introduced after prevalidation phase. When cell viability (evaluated MTT reduction test) used as endpoint, predictive ability both EpiDerm EPISKIN considered sufficient justify their progression 2, while SIFT judged be inadequate. Since provided false predictions around border (a Draize score 2), release cytokine, interleukin-1alpha (IL-1alpha), also determined. model laboratories, chemicals. main endpoint measured viability. samples gave assay results above threshold 50% viability, IL-1alpha measured, determine additional improve For EPISKIN, sensitivity 75% specificity 81% (MTT only); combination assays, increased 91%, 79%. EpiDerm, 57% 85% only), capacity not improved measurement release. Following independent peer review, April 2007 Scientific Advisory Committee endorsed scientific validity replacement method, method identifying part tiered testing strategy. This new alternative approach will probably first use toxicity replace Europe internationally, since, very near future, OECD Test Guidelines proposed regulatory acceptance