Local lymph node assay: validation assessment for regulatory purposes.

For the prediction of skin sensitization potential of substances, the murine local lymph node assay (LLNA) is an alternative to the widely used guinea pig tests. For more than 10 years, this method has undergone extensive development, evaluation, and validation. In this review, the validation status of the LLNA is considered, specifically with regard to its use for regulatory identification of skin sensitization hazards. The LLNA is a method for the predictive identification of chemicals that have a potential to cause skin sensitization. Activity is measured as a function of lymph node cell proliferative responses stimulated by topical application of test chemicals. The LLNA has successfully passed all reasonable validation stages. It provides a reliable and relevant source of predictive skin sensitization data, which unlike results from guinea pig tests, are reproducible from laboratory to laboratory. In summary, the LLNA is now ready for acceptance as a viable and complete alternative to traditional methods, offering a substantial reduction in animal numbers and refinement opportunities without compromising the standards for the identification of important skin sensitizers.