PMID- 37116738
OWN - NLM
STAT- MEDLINE
DCOM- 20230605
LR  - 20230605
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 141
DP  - 2023 Jun
TI  - Specificity of the local lymph node assay (LLNA) for skin sensitisation.
PG  - 105402
LID - S0273-2300(23)00070-3 [pii]
LID - 10.1016/j.yrtph.2023.105402 [doi]
AB  - 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.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Roberts, David W
AU  - Roberts DW
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Liverpool, L3 3AF, UK. Electronic address: d.w.roberts@ljmu.ac.uk.
FAU - Kimber, Ian
AU  - Kimber I
AD  - Faculty of Biology, Medicine and Health, University of Manchester, Manchester, 
      M13 9PT, UK.
FAU - Basketter, David A
AU  - Basketter DA
AD  - DABMEB Consultancy Ltd, Abbey View, Abbey St, Kingswood, Wotton-under-Edge, GL12 
      8RN, UK.
LA  - eng
PT  - Journal Article
DEP - 20230426
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Irritants)
RN  - 0 (Allergens)
SB  - IM
MH  - Humans
MH  - *Local Lymph Node Assay
MH  - Skin
MH  - Irritants/chemistry
MH  - *Dermatitis, Allergic Contact/etiology/pathology
MH  - Allergens/toxicity
MH  - Lymph Nodes
OTO - NOTNLM
OT  - False positives
OT  - Hydrophobicity
OT  - Potency categories
OT  - Skin sensitisation assays
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/04/29 06:04
MHDA- 2023/06/05 06:43
CRDT- 2023/04/28 19:28
PHST- 2023/02/08 00:00 [received]
PHST- 2023/04/13 00:00 [revised]
PHST- 2023/04/25 00:00 [accepted]
PHST- 2023/06/05 06:43 [medline]
PHST- 2023/04/29 06:04 [pubmed]
PHST- 2023/04/28 19:28 [entrez]
AID - S0273-2300(23)00070-3 [pii]
AID - 10.1016/j.yrtph.2023.105402 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2023 Jun;141:105402. doi: 10.1016/j.yrtph.2023.105402. 
      Epub 2023 Apr 26.