In line with the 7European legislations have heightened the need for accepted test. The reconstructed human epidermis EpiSkin™ and SkinEthic™ RHE “42 bis” test methods were validated by ECVAM as stand alonereplacement tests for the prediction of acute skin irritation according to both former and recent implemented Globally Harmonizationth amendment deadlines, European Union bans the in vivo skin irritation assessment on ingredients for cosmetic purposes.in vitro skin irritation test to replace the regulatory Draize skin irritationSystem (GHS) classifications applied in Europe. Therefore, the test methods were endorsed in the EU test method B.46 and in the in vitro skinirritation OECD Test Guideline 439. Evaluation using the methods directly addresses the initial steps of the inflammatory cascade/mechanismof action i.e. cell and tissue damages resulting in localized trauma. The global predictive capacities (specificity, sensitivity and accuracy)of the EpiSkin™ (designated the Validated Reference Method in the in the OECD guideline), and the SkinEthic™ RHE demonstrate that thesemethodologies are applicable to substances and mixtures with a wide range of physico-chemical.