AN ALTERNATIVE STRATEGY TO THE USE OF GUINEA-PIGS FOR THE IDENTIFICATION OF SKIN SENSITIZATION HAZARD

For over half a century, guinea pig methods have dominated the field o f toxicology concerned with the identification of skin sensitizers. Sp ecific protocols, for example the guinea pig maximization test (GPMT), have been pre-eminent in the identification of skin sensitization haz ard for regulatory purposes. However, there are increasingly several f orces driving change, not least animal use/welfare considerations. In response to this and to address the need for a rapid screen for chemic al allergens, an alternative strategy has been developed. In the first instance, a chemical is assessed by a computer-based expert system. T his system is constructed from some 50 rules describing the key chemic ally reactive substructures of known skin sensitizers. The output from the expert system is also evaluated in the light of the understanding of the skin penetration characteristics of the chemical. In this way, and without use of animals, the likelihood that a chemical represents a skin sensitization hazard is assessed based on the two key characte ristics of a skin sensitizer: (1) its direct or indirect ability to re act with skin protein (i.e. does it contain a structural alert?); and (2) the ability of the chemical to partition into the appropriate epid ermal compartment. When the chemical does possess a structural alert a nd has the capacity tb penetrate skin sufficiently, then it may be reg arded as a potential skin sensitizer. Subsequent to this screening pha se, if necessary the chemical may be assessed in the murine local lymp h node assay. This assay is quicker and cheaper than traditional guine a pig assays and importantly is less stressful to the fewer animals th at it requires. The assay is well validated and produces objective res ults which are equivalent to the GPMT in terms of identifying signific ant skin sensitization hazard. In this paper, the above strategy is de scribed in more detail, focusing on its relevance to hazard identifica tion and its value in animal welfare terms. It is concluded that the s trategy provides an important opportunity for both substantial reducti on and refinement of animal use in a manner which will not compromise the existing standard of classification and labelling of skin sensitiz ation hazard in the European Union.