A REPRODUCIBLE SKIN MODEL FOR DERMAL SAFETY AND EFFICACY TESTING.

The utility of any toxicological test system or method critically depends on the short and long term reproducibility of the method. Over the past 6 years, histological observations and quantitative quality control test methods utilizing the MTT assay have established a high level of intra-lot and inter-lot reproducibility for MatTek’s organotypic skin model, EpiDerm™. Interestingly, the MTT assay can distinguish between standard EpiDerm (EPI-200) and hydrocortisone free EpiDerm (EPI-200-HCF) whereas histologically, the tissues are remarkably similar. Quality control testing on each lot of tissue consists of exposing the tissue to 1% Triton X-100 (TX) and a negative control (NC), ultrapure water. Using the MTT assay, an exposure time which reduced the tissue viability to 50% (ET-50) was determined. For EPI-200 produced in 1995 (112 lots), the ET-50 for TX averaged 6.64+0.79 hrs; the optical density (OD) for NC was 1.495+0.126; during the first 9 months of calendar year 2000 (89 lots), the averages were 6.76+1.11 hrs and 1.627+0.164, respectively. For EPI-200-HCF, used for cytokine release studies, the ET-50 averaged 9.02+1.16 hrs and the NC was 1.490+0.165. Assays for dermal irritancy, corrosivity, and phototoxicity have been developed using EpiDerm. Correlation of in vivo irritation data to in vitro assay results for 4 sets of materials gave correlation coefficients of 0.85 and 0.96. For corrosivity, sensitivity of 87.5%, and specificity of 86.1% were obtained in a multi-lab, international blinded study of 24 unknowns. In a similar multi-lab phototoxicity study on 10 blinded materials, the sensitivity and specificity were 86.7% and 93.3%, respectively. Thus, the EpiDerm tissue model provides a reproducible, non-animal means to test materials and/or products for a variety of skin related issues.

Corrosion, Corrosivity, Corrosivity testing, Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Dermal corrosion, Dermal irritancy, Dermal irritancy testing, Dermal irritation, Dermal safety, ECVAM, Efficacy testing, EpiDerm, EpiDerm hydrocortisone free, MTT, MTT ET-50 tissue viability assay, MTT assay, Phototoxicity, Reproducibility, Reproducible, Skin corrosion, Skin corrosivity, Skin irritancy, Skin irritation, Skin model, Sun screens, UVA, UVB