ATLA::Alternatives to Laboratory Animals

Volume 26, Number 5

An evaluation of the proposed OECD testing strategy for skin corrosion.

ATLA 26, 709-720, September/October 1998

Andrew P. Worth,1 Julia H. Fentem,1 Michael Balls,1 Philip A. Botham,2 Rodger D. Curren,3 Lesley K. Earl,4 David J. Esdaile5 and Manfred Liebsch6

1ECVAM, JRC Environment Institute, 21020 Ispra (VA), Italy; 2Central Toxicology Laboratory, ZENECA, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK; 3Institute for In Vitro Sciences, 21 Firstfield Road, Gaithersburg, MD 20878, USA; 4SEAC Toxicology Unit, Unilever Research, Colworth House, Sharnbrook, Bedfordshire MK44 1LQ UK; 5Rhône Poulenc Agro, 355 rue Dostoievski, 06903 Sophia Antipolis Cedex, France; 6ZEBET, BgVV, Diedersdorfer Weg 1, 12277 Berlin, Germany

SUMMARY

The use of testing strategies which incorporate a range of alternative methods and which use animals only as a last resort is widely considered to provide a reliable way of predicting chemical toxicity while minimising animal testing. The widespread concern over the severity of the Draize rabbit test for assessing skin irritation and corrosion led to the proposal of a stepwise testing strategy at an OECD workshop in January 1996. Subsequently, the proposed testing strategy was adopted, with minor modifications, by the OECD Advisory Group on Harmonization of Classification and Labelling. This article reports an evaluation of the proposed OECD testing strategy as it relates to the classification of skin corrosives. By using a set of 60 chemicals, an assessment was made of the effect of applying three steps in the strategy, taken both indindually and in sequence. The results indicate that chemicals can be classified as corrosive (C) or non-corrosive (NC) with sufficient reliability by the sequential application of three alternative methods, i.e., structure-activity relationships (where available) pH measurements, and a single in vitro method (either the rat skin transcutaneous electrical resistance (TER) assay or the EPISKINTM assay). It is concluded that the proposed OECD strategy for skin corrosion can be simplified without compromising its predictivity. For example, it does not appear necessary to measure acid/alkali reserve (buffering capacity) in addition to pH for the classification of pure chemicals.

Keywords: corrosion, skin, testing strategy, structure-activity relationship, physicochemical, in vitro