PMID- 21803111 OWN - NLM STAT- MEDLINE DCOM- 20120406 LR - 20110907 IS - 1096-0295 (Electronic) IS - 0273-2300 (Linking) VI - 61 IP - 1 DP - 2011 Oct TI - Skin irritation, false positives and the local lymph node assay: a guideline issue? PG - 137-40 LID - 10.1016/j.yrtph.2011.07.004 [doi] AB - Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Basketter, David A AU - Basketter DA AD - Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M139PT, UK. dabmebconsultancyltd@me.com FAU - Kimber, Ian AU - Kimber I LA - eng PT - Journal Article PT - Review DEP - 20110722 PL - Netherlands TA - Regul Toxicol Pharmacol JT - Regulatory toxicology and pharmacology : RTP JID - 8214983 RN - 0 (Irritants) SB - IM MH - *Dermatitis, Allergic Contact/immunology/pathology MH - *Dermatitis, Contact/immunology/pathology MH - False Positive Reactions MH - Guidelines as Topic MH - Humans MH - *Irritants MH - *Local Lymph Node Assay MH - Skin Diseases/*chemically induced/immunology/pathology EDAT- 2011/08/02 06:00 MHDA- 2012/04/07 06:00 CRDT- 2011/08/02 06:00 PHST- 2011/06/03 00:00 [received] PHST- 2011/07/06 00:00 [revised] PHST- 2011/07/06 00:00 [accepted] PHST- 2011/08/02 06:00 [entrez] PHST- 2011/08/02 06:00 [pubmed] PHST- 2012/04/07 06:00 [medline] AID - S0273-2300(11)00149-8 [pii] AID - 10.1016/j.yrtph.2011.07.004 [doi] PST - ppublish SO - Regul Toxicol Pharmacol. 2011 Oct;61(1):137-40. doi: 10.1016/j.yrtph.2011.07.004. Epub 2011 Jul 22.