IN VITRO SKIN CORROSION TEST: LONG TERM REPRODUCIBILITY AND RELIABILITY FOR A REGULATORY ACCEPTED METHOD.

This study by scientists at the Institute for In Vitro Sciences (IIVS) and MatTek Corp. demonstrated the long term reproducibility and reliability of MatTek’s EpiDerm tissue model and the EpiDerm Dermal Corrosion assay protocol, as required by regulators. The EpiDerm skin corrosion test was repeated with the commercially available test substances previously used in both ECVAM validation studies, and the data obtained show very good correlation over a period of SEVEN (7) YEARS. The potential for chemicals to cause skin effects such as corrosion is a concern of industrial toxicologists in their assessments of possible worker and consumer safety issues. Moreover, the U.S. Department of Transportation (DOT), the new regulation on the Registration, Evaluation and Authorization of Chemicals (REACH), and other international and national regulatory agencies require that substances should be labeled with regard to skin corrosivity potential for tissue destruction. In the past, skin corrosion assessments were based on tests involving topical application of test substances to the skin of rabbits. However, based on two ECVAM Validation studies performed during 1996-2000 with two reconstructed human skin models (EpiDerm™ and EPISKIN), the OECD approved use of these skin models as regulatory accepted methods (OECD TG 431) replacing the in vivo test. In the present study by scientists at the Institute for In Vitro Science (IIVS) and MatTek Corp., the EpiDerm skin corrosion test was repeated with the commercially available test substances previously used in both ECVAM validation studies. The aim was to demonstrate the long term reproducibility and reliability of the EpiDerm model and the method, as required by regulators. The data obtained show very good correlation over a period of 7 years. A secondary aim of this study was to evaluate the assay prediction model for materials that interfere with the MTT endpoint used in the method. This presentation summarizes data obtained with the EpiDerm skin corrosion assay and demonstrates recent improvements which allow the testing materials interfering with the MTT endpoint. Study Conclusions: • The EpiDerm Skin Corrosivity assay protocol is applicable to a diverse group of chemicals (both liquids and solids), including organic acids and bases, neutral organics, inorganic acids and bases, electrophiles and phenols. • The sensitivity and specificity of the EpiDerm skin corrosivity exceeded 83% in both the current study and during the ECVAM sponsored validation study in 1998-2000. • For the 18 corrosive chemicals tested, the modified protocol increased the specificity of the EpiDerm Skin Corrosivity assay from 83% to 100%. Interlaboratory reproducibility of the procedure using freeze-killed tissues will be evaluated in an interlaboratory trial between IIVS and MatTek.

Corrosion, Corrosivity assay, EpiDerm, Freeze-killed tissues, Frozen tissue, Long term reproducibility , MTT, MTT assay, REACH, Regulatory accepted method, Skin corrosion

1,2-diaminopropane , 1,9-decadiene, 1-(2-Aminoethyl) piperazine, 2-tert. Butylphenol , 4-amino-1,2,4-triazole, 4-methylthio-benzaldehyde, Acrylic acid , Allyl bromide, Boron trifluoride dihydrale , Carvacrol, Dimethylisopropylamine , Eugenol, Ferric chloride (Iron III chloride), Guajacol (o-Methoxyphenol), Isostearic acid, Lauric acid (Dodecanoic acid), Melhaerolein, N.N-Dimethyldiprolylenetriamine , Octanoic acid (Caprylic acid) , Octanoic/decanoic acids (55:45), Octanoic/decanoic acids (65:35) , Phenethyl bromide, Phosphorous tribromide , Potassium hydroxide (10% aq.) , Sodium carbonate (50% aq.) , Sodium lauryl sulfate (20% aq.), Sulfamic acid, Sulfuric acid (10%) , Tetrachloroethylene, n-Heptylamine