Validation of Alternative Endpoints for the LLNA: General Considerations

Before being considered for regulatory use, every in vitro or in vivo method should provide evidence of its reliability and reproducibility in a validation exercise. Validation procedures are becoming more flexible to accommodate the different needs including the evaluation of those tests which are considered similar or equivalent to an already validated one. In the field of skin sensitisation, there is considerable interest in developing modifications to the standard murine Local Lymph Node Assay (LLNA) to encompass non-radioactive endpoints. These methods, once sufficiently advanced and standardised, will need to be validated. For this purpose, Performance Standards for the LLNA are needed to guide such appraisal. In order to decide which type of evaluation a modified method needs to undergo to prove its validity, consideration has to be given as to whether minor or major modifications have been introduced compared to the validated test.JRC.I.2-In-vitro Toxicolog