PMID- 27477089
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20170309
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 80
DP  - 2016 Oct
TI  - Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin 
      sensitisation potency. Part 3. Apparent discrepancies between LLNA and GPMT 
      sensitisation potential: False positives or differences in sensitivity?
PG  - 260-7
LID - S0273-2300(16)30208-2 [pii]
LID - 10.1016/j.yrtph.2016.07.018 [doi]
AB  - The Local Lymph Node Assay (LLNA) is the gold standard regulatory toxicology test 
      for skin sensitisation along with the guinea pig maximisation test (GPMT). 
      Compared with the GPMT, LLNA uses fewer animals, it is quantitative, and it gives 
      a numerical prediction of potency. However several concerns have been raised with 
      this assay, mainly related to false positives and false negatives. Over the 
      years, many authors, including the developers of the assay, have presented cases 
      where there have been discrepancies between the GMPT and LLNA results. Several 
      theories have been put forward for these discrepancies, the main one being the 
      "over-sensitivity" of the GPMT. This paper analyses the data from a systematic 
      study, published in three papers from 2008 to 2011, covering several classes of 
      chemicals, in particular unsaturated fatty acids, sugar surfactants and 
      ethoxylated alcohols, with many cases of chemicals testing positive in the LLNA 
      being negative in the GPMT. Based on consideration of reaction chemistry and 
      structural alerts, it is concluded that these discrepancies are not LLNA false 
      positives, but can be rationalised in terms of the different protocols of the 
      assays.
CI  - Copyright (c) 2016 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, United Kingdom. Electronic address: D.W.Roberts@ljmu.ac.uk.
FAU - Schultz, Terry W
AU  - Schultz TW
AD  - The University of Tennessee, College of Veterinary, 2407 River Drive, Knoxville, 
      TN, 37996, USA.
FAU - Api, Anne Marie
AU  - Api AM
AD  - Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff 
      Lake, NJ, 07677, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160729
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Irritants)
SB  - IM
MH  - Administration, Cutaneous
MH  - Animals
MH  - Data Mining
MH  - Databases, Factual
MH  - Dermatitis, Allergic Contact/*etiology/immunology
MH  - Dose-Response Relationship, Drug
MH  - False Positive Reactions
MH  - Guinea Pigs
MH  - Humans
MH  - Irritants/chemistry/metabolism/*toxicity
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/*drug effects/pathology
MH  - Mice
MH  - *Models, Molecular
MH  - Molecular Structure
MH  - Reproducibility of Results
MH  - Skin/*drug effects/immunology/metabolism
MH  - Skin Absorption
MH  - Species Specificity
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Autoxidation
OT  - Surfactants
OT  - Unsaturated fatty acids
EDAT- 2016/08/02 06:00
MHDA- 2017/03/10 06:00
CRDT- 2016/08/02 06:00
PHST- 2016/06/18 00:00 [received]
PHST- 2016/07/25 00:00 [revised]
PHST- 2016/07/26 00:00 [accepted]
PHST- 2016/08/02 06:00 [entrez]
PHST- 2016/08/02 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
AID - S0273-2300(16)30208-2 [pii]
AID - 10.1016/j.yrtph.2016.07.018 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2016 Oct;80:260-7. doi: 10.1016/j.yrtph.2016.07.018. 
      Epub 2016 Jul 29.