title: The local lymph node assay and skin sensitization: a cut-down screen to reduce animal requirements?
abstract: The local lymph node assay (LLNA), an alternative approach to skin-sensitizing testing, has made a significant contribution to animal welfare by permitting a reduction and refinement of animal use. Although there is clearly an aspiration to eliminate the use of animals in such tests, it is appropriate also to consider other opportunities for refinement and reduction of animal use. We have therefore explored the use of a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitizing activity of a large number of chemicals, as will be the case under the auspices of registration, evaluation and authorization of chemicals (REACH). Using an existing LLNA database of 211 chemicals, we have examined whether a cut-down assay comprising a single high-dose group and a concurrent vehicle control would provide a realistic approach for screening chemicals for sensitizing potential. The analyses reported here suggest this is the case. We speculate that the animal welfare benefits may be enhanced further by reducing the number of animals per experimental group. However, a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitization potencies.
authors.affiliation: Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. ian.kimber@syngenta.com
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Betts
authors.forename: G Frank
authors.initials: GF
authors.lastname: Gerberick
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Ryan
authors.forename: Petra S
authors.initials: PS
authors.lastname: Kern
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Patlewicz
authors.forename: David A
authors.initials: DA
authors.lastname: Basketter
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D016208:Databases, Factual; D017449:Dermatitis, Allergic Contact / Q000209:etiology; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D023441:Local Lymph Node Assay; D051379:Mice; D008808:Mice, Inbred CBA; D018675:Toxicity Tests / Q000379:methods*