title: Performance standards and alternative assays: practical insights from skin sensitization.
abstract: To encourage the development and validation of alternative toxicity test methods, the effort required for validation of test methods proposed for regulatory purposes should be minimized. Performance standards (PS) facilitate efficient validation by requiring limited testing. Based on the validated method, PS define accuracy and reliability values that must be met by the new similar test method. The OECD adopted internationally harmonized PS for evaluating new endpoint versions of the local lymph node assay (LLNA). However, in the process of evaluating a lymph node cell count alternative (LNCC), simultaneous conduct of the regulatory LLNA showed that this standard test may not always perform in perfect accord with its own PS. The LNCC results were similar to the concurrent LLNA. Discrepancies between PS, LLNA and LNCC were largely associated with "borderline" substances and the variability of both endpoints. Two key lessons were learned: firstly, the understandable focus on substances close to the hazard classification borderline are more likely to emphasise issues of biological variability, which should be taken into account during the evaluation of results; secondly, variability in the results for the standard assay should be considered when selecting reference chemicals for PS.
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany. susanne.kolle@basf.com
authors.forename: Susanne N
authors.initials: SN
authors.lastname: Kolle
authors.forename: David A
authors.initials: DA
authors.lastname: Basketter
authors.forename: Silvia
authors.initials: S
authors.lastname: Casati
authors.forename: William S
authors.initials: WS
authors.lastname: Stokes
authors.forename: Judy
authors.initials: J
authors.lastname: Strickland
authors.forename: Bennard
authors.initials: B
authors.lastname: van Ravenzwaay
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Vohr
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
mesh_terms: D000485:Allergens / Q000145:classification / Q000633:toxicity*; D000826:Animal Testing Alternatives / Q000379:methods* / Q000592:standards; D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology; D023441:Local Lymph Node Assay; D015203:Reproducibility of Results; D023422:Skin Irritancy Tests; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D000485:Allergens