LLNALocal Lymph Node Assay
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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.
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Because of the complexity of the skin sensitization process, it is generally agreed that a single alternative test method is not sufficient to substitute animal models (e.g., LLNA) and that a combination of methods in integrated approaches to testing and assessment (IATA) will be required (Jowsey et al., 2006; Reisinger et al., 2015; Corsini et al., 2014; Ezendam et al., 2016; Jaworska, 2016).
It is likely that subsequent validation and acceptance of alternatives will have a shorter timeline because assays such as LLNA have paved the way, but probably not by much.
For example, the mouse LLNA exposes mice to a chemical and measures response in lymph nodes (Gerberick et al., 2001).
Three common sensitization tests require the use of animals: the guinea pig maximization test (the most widely recognized, which uses 15 guinea pigs per extract), the Buehler closed patch test (also with guinea pigs), and the murine local lymph node assay (LLNA).
Mainly, the murine Local Lymph Node Assay (LLNA) continues to be used today.
The assessment of a substance's skin sensitization potential has been traditionally based on data derived from animal tests, such as the guinea pig based tests described in OECD TG 406 (OECD, 1992) or the murine local lymph node assay (LLNA) described in OECD TG 429 (OECD, 2002, 2010).
The murine Local Lymph Node Assay (LLNA) (Gerberick et al., 2007), followed by the Guinea Pig Maximization Test (Magnusson and Kligman, 1969), has for many years been the preferred assay for skin sensitization testing as the LLNA is able to provide data for both hazard identification and characterization, including skin sensitizer potency information.
The reference chemicals are comprised of a panel of different sensitizer categories (minimal to severe and non-sensitizers), as defined by the animal-based Local Lymph Node Assay (LLNA).
The defined approaches for skin sensitization have comparable performance to the standard animal test, the Local Lymph Node Assay (LLNA), for identifying potential skin allergens.
Quantitative data on sensitization potency of chemicals has long been derived from in vivo data obtained with the local lymph node assay (LLNA) in mice.