The SKINTEX Method is based on a two-compartment physico-chemical model which includes a Biomembrane Barrier in compartment one and an organized macromolecular matrix in compartment two. Test samples absorb onto or permeate through the keratin/collagen Biomembrane Barrier and then can interact with the organized macromolecular matrix. Changes in the integrity of the barrier release a dye indicator: Changes in the matrix can alter its transparency. The sum of these two responses is read spectrophotometrically at 470nm. An early investigation of 950 chemicals and formulations in the SKINTEX System produced results which were 89% concordance to in vivo Draize dermal irritation results obtained with 24-hour occluded application of test samples with-out abrasion and standard scoring. Alkaline materials were analyzed in a specialized SKINTEX AMA Protocol. In this early study, the model did not distinguish nonirritant test materials and formulation with PDII(Primary Dermal Irritation Index)in the range from 0 to 1.2, A High Sensitivity Assay Protocol(HSA)was developed to amplify the changes in both compartments of this model and provide more accurate calibration of these changes. A study of 60 low irritation test samples including cosmetics, household products, chemicals and petro-chemicals distinguished nonirritants with PDII $leq$ 0.7 for 26 of 30 nonirritants. A second protocol was developed to evaluate the SKINTEX model predictability with respect to human irritation. The Human Response Assay (HRA )has been optimized based on differences in penetration and irritation responses in humans and rabbits. An additional 32 test materials with different mechanisms and degrees of dermal toxicity were evaluated by the HRA. These in vitro results were 86% concordant to human patch test results. In order to further evaluate this model, a Standard Chemical Labelling (SCL) Protocol was developed to optimize this system to predict Draize dermal irritation results after a 4-hour application of the test material. In a study of 52 chemicals including acids, bases, solvents, salts, surfactants and preservatives, the SCL results demonstrated 85% concordance to Draize results for a 4-hour application of test samples on non-abraded rabbit skin. The SKINTEX System, including three specialized protocols, provided results which demonstrated good correlation to the endpoint of dermal irritation in man and rabbits at different application times.