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 DRAFT GUIDELINE

                                                                May 20, 2004 (1st Version)

OECD GUIDELINE FOR THE TESTING OF CHEMICALS

DRAFT PROPOSAL FOR A NEW GUIDELINE: 435

In Vitro Membrane Barrier Test Method for Skin Corrosion

INTRODUCTION

1.  Skin corrosion refers to the production of irreversible damage to the skin, manifested as visible necrosis through the epidermis and into the dermis, following the application of a test material [as defined by the United Nations (UN) Globally Harmonised System for the Classification and Labelling of Chemical Substances and Mixtures (GHS)] (1). This Test Guideline provides an in vitro procedure by which the assessment of corrosivity is not carried out in live animals.

2.  A number of in vitro test methods have been proposed as alternatives for the standard in vivo rabbit skin procedure (OECD TG 404)(2) used to identify corrosive substances. This Test Guideline is for an in vitro membrane barrier test method that can be used to identify corrosive substances.  The test method utilizes an artificial membrane designed to respond to corrosive substances in a manner similar to animal skin in situ.

3.  Skin corrosivity has traditionally been assessed by applying the test substance to the skin of living animals and assessing the extent of tissue damage after a fixed period of time (2)(3). The UN GHS tiered testing and evaluation strategy for the assessment and classification of skin corrosivity allows for the use of validated and accepted in vitro test methods (1).  In this tiered strategy, positive results from in vitro test methods can be used to classify a substance as corrosive without the need for animal testing, thus reducing and refining the use of animals in testing. Substances that are negative undergo additional testing in accordance with the tiered testing strategy (1)(see supplement to Test Guideline 404(2)). The use of in vitro test methods to identify corrosive substances can therefore avoid the pain and distress that might occur when animals are used for this purpose.

4.  Validation studies have been completed for an in vitro membrane barrier test method commercially available as Corrositex® (4)(5)(6).  Based on its acknowledged validity, this validated reference test method has been recommended for use as part of a tiered testing strategy for assessing the dermal corrosion hazard potential of chemicals (5). Before an in vitro membrane barrier test method for skin corrosion can be used for regulatory purposes, its reliability, accuracy, and limitations for its proposed use should be determined to ensure that it is comparable to that of the validated reference test method (7)(8)(9)(10).

5.  A limitation of the validated reference test method (5) is that many non-corrosive chemicals and chemical mixtures and some corrosive chemicals and chemical mixtures do not qualify for testing. Aqueous substances with a pH in the range of 4.5 to 8.5 often do not qualify for testing; however, 85% of chemicals tested in this pH range were non-corrosive in animal tests (5). The in vitro membrane barrier test methods may be used to test solids (soluble or insoluble in water), liquids (aqueous or non-aqueous), and emulsions; however, test chemicals and chemical mixtures not causing a colour change in the Chemical Detection System (CDS) of the validated reference test method cannot be tested with the membrane barrier test method and should be tested using other test methods. The samples may be pure chemicals, dilutions, formulations, or waste. No prior treatment of the sample is required.

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