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 of toxicology concerned with the identification of skin sensitizers. Specific protocols, for example the guinea pig maximization test (GPMT), have been pre-eminent in the identification of skin sensitization hazard for regulatory purposes. However, there are increasingly several forces driving change, not least animal use/welfare considerations. In response to this and to address the need for a rapid screen for chemical allergens, an alternative strategy has been developed. In the first instance, a chemical is assessed by a computer-based expert system. This system is constructed from some 50 rules describing the key chemically 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 characteristics of a skin sensitizer: (1) its direct or indirect ability to react with skin protein (i.e. does it contain a structural alert?); and (2) the ability of the chemical to partition into the appropriate epidermal compartment. When the chemical does possess a structural alert and has the capacity to penetrate skin sufficiently, then it may be regarded as a potential skin sensitizer. Subsequent to this screening phase, if necessary the chemical may be assessed in the murine local lymph node assay. This assay is quicker and cheaper than traditional guinea pig assays and importantly is less stressful to the fewer animals that it requires. The assay is well validated and produces objective results which are equivalent to the GPMT in terms of identifying significant skin sensitization hazard. In this paper, the above strategy is described in more detail, focusing on its relevance to hazard identification and its value in animal welfare terms. It is concluded that the strategy provides an important opportunity for both substantial reduction and refinement of animal use in a manner which will not compromise the existing standard of classification and labelling of skin sensitization hazard in the European Union.
Basketter
D A
DA
Unilever Environmental Safety Laboratory, Sharnbrook, Bedford, UK.
Scholes
E W
EW
Chamberlain
M
M
Barratt
M D
MD
D000826:Animal Testing Alternatives; D000827:Animal Welfare; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D005103:Expert Systems; D006168:Guinea Pigs; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D012867:Skin / Q000187:drug effects*; D012869:Skin Absorption; D012882:Skin Tests / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*