The local lymph node assay: a viable alternative to currently accepted skin sensitization tests.

The prospective identification of skin sensitizing chemicals is a vital prerequisite for their proper risk management. Traditionally this has been achieved largely by the conduct of guinea pig assays such as the maximization and Buehler tests. These methods are recommended by the Organisation for Economic Cooperation and Development (OECD) and are required by the European Union (EU) for the evaluation of new substances. However, a novel mechanistically based method, the local lymph node assay (LLNA), has been the focus of substantial validation activity in recent years. This material is reviewed in this paper. It is shown that the LLNA has been validated successfully by five interlaboratory assessments as well as by comparisons with guinea pig tests and human data. The method also offers clear advantages to the user in terms of objectivity, time and cost, and delivers important animal welfare benefits. In consequence, it is recommended that the LLNA be formally adopted by the OECD in Guideline 406 and accepted by the EU and US EPA as a method suitable for the classification of the skin sensitizing potential of chemicals.