Roberts, DW, Kimber, I and Basketter, DA (2023) Specificity of the local lymph node assay (LLNA) for skin sensitisation. Regulatory Toxicology and Pharmacology, 141. ISSN 0273-2300

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Abstract

The local lymph node assay (LLNA) has provided a large dataset against which performance of non-animal approaches for prediction of skin sensitisation potential and potency can be assessed. However, a recent comparison of LLNA results with human data has argued that LLNA specificity is low, with many human non-sensitisers, particularly hydrophobic chemicals, being false positives. It has been suggested that such putative false positives result from hydrophobic chemicals causing cytotoxicity, which induces irritancy, in turn driving non-specific lymphocyte proliferation. This paper finds that the apparent reduced specificity of the LLNA largely reflects differences in definitions of the boundaries between weak skin sensitisers and non-sensitisers. A small number of LLNA false positives may be due to lymphocyte proliferation without skin sensitisation, but most alleged ‘false’ positives are in fact very weak sensitisers predictable from structure-activity considerations. The evidence does not support the hypothesis for hydrophobicity-induced false positives. Moreover, the mechanistic basis is untenable. Sound LLNA data, appropriately interpreted, remain a good measure of sensitisation potency, applicable across a wide hydrophilicity-hydrophobicity range. The standard data interpretation protocol enables detection of very low levels of sensitisation, irrespective of regulatory significance, but there is scope to interpret the data to give focus on regulatory significance.

Item Type:	Article
Uncontrolled Keywords:	Lymph Nodes; Skin; Humans; Dermatitis, Allergic Contact; Allergens; Irritants; Local Lymph Node Assay; False positives; Hydrophobicity; Potency categories; Skin sensitisation assays; Humans; Local Lymph Node Assay; Skin; Irritants; Dermatitis, Allergic Contact; Allergens; Lymph Nodes; 1115 Pharmacology and Pharmaceutical Sciences; Toxicology
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RL Dermatology R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	Elsevier
SWORD Depositor:	A Symplectic
Date Deposited:	24 Jul 2023 08:06
Last Modified:	24 Jul 2023 08:15
DOI or ID number:	10.1016/j.yrtph.2023.105402
URI:	https://researchonline.ljmu.ac.uk/id/eprint/20467

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