title: Immunophenotyping does not improve predictivity of the local lymph node assay in mice.
abstract: The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry-based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I-A(κ) and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non-irritating sensitizers and non-sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA.
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, Z470, 67056, Ludwigshafen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Strauss
authors.forename: Susanne N
authors.initials: SN
authors.lastname: Kolle
authors.forename: Naveed
authors.initials: N
authors.lastname: Honarvar
authors.forename: Martina
authors.initials: M
authors.lastname: Dammann
authors.forename: Sibylle
authors.initials: S
authors.lastname: Groeters
authors.forename: Frank
authors.initials: F
authors.lastname: Faulhammer
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.forename: Bennard
authors.initials: B
authors.lastname: van Ravenzwaay
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism; D005260:Female; D006241:Haptens / Q000633:toxicity*; D016130:Immunophenotyping; D007509:Irritants / Q000633:toxicity*; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008808:Mice, Inbred CBA; D008954:Models, Biological; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000954:Antigens, Surface; D006241:Haptens; D007509:Irritants; D013501:Surface-Active Agents
keywords: LLNA; immunophenotyping; mice; predicitivity; skin sensitization