title: Analysis of the Local Lymph Node Assay (LLNA) variability for assessing the prediction of skin sensitisation potential and potency of chemicals with non-animal approaches.
abstract: The knowledge of the biological mechanisms leading to the induction of skin sensitisation has favoured in recent years the development of alternative non-animal methods. During the formal validation process, results from the Local Lymph Node Assay (LLNA) are generally used as reference data to assess the predictive capacity of the non-animal tests. This study reports an analysis of the variability of the LLNA for a set of chemicals for which multiple studies are available and considers three hazard classification schemes: POS/NEG, GHS/CLP and ECETOC. As the type of vehicle used in a LLNA study is known to influence to some extent the results, two analyses were performed: considering the solvent used to test the chemicals and without considering the solvent. The results show that the number of discordant classifications increases when a chemical is tested in more than one solvent. Moreover, it can be concluded that study results leading to classification in the strongest classes (1A and EXT) seem to be more reliable than those in the weakest classes. This study highlights the importance of considering the variability of the reference data when evaluating non-animal tests.
authors.affiliation: Joint Research Centre, European Commission, Ispra, Italy.
authors.forename: Coralie
authors.initials: C
authors.lastname: Dumont
authors.affiliation: Joint Research Centre, European Commission, Ispra, Italy.
authors.forename: João
authors.initials: J
authors.lastname: Barroso
authors.affiliation: Joint Research Centre, European Commission, Ispra, Italy.
authors.forename: Izabela
authors.initials: I
authors.lastname: Matys
authors.affiliation: Joint Research Centre, European Commission, Ispra, Italy.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worth
authors.affiliation: Joint Research Centre, European Commission, Ispra, Italy. Electronic address: silvia.casati@ec.europa.eu.
authors.forename: Silvia
authors.initials: S
authors.lastname: Casati
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D017449:Dermatitis, Allergic Contact; D006241:Haptens / Q000145:classification / Q000633:toxicity*; D023441:Local Lymph Node Assay; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D006241:Haptens
keywords: Alternative methods; ECETOC; GHS/CLP; LLNA variability; Validation