PMID- 27470439
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 2. The biological variability of the murine Local 
      Lymph Node Assay (LLNA) for skin sensitisation.
PG  - 255-9
LID - S0273-2300(16)30196-9 [pii]
LID - 10.1016/j.yrtph.2016.07.013 [doi]
AB  - The Local Lymph Node Assay (LLNA) is the most common in vivo regulatory 
      toxicology test for skin sensitisation, quantifying potency as the EC3, the 
      concentration of chemical giving a threefold increase in thymidine uptake in the 
      local lymph node. Existing LLNA data can, along with clinical data, provide 
      useful comparator information on the potency of sensitisers. Understanding of the 
      biological variability of data from LLNA studies is important for those 
      developing non-animal based risk assessment approaches for skin allergy. Here an 
      existing set of 94 EC3 values for 12 chemicals, all tested at least three times 
      in the same vehicle have been analysed by calculating standard deviations (SD) 
      for logEC3 values. The SDs range from 0.08 to 0.22. The overall SD for the 94 
      logEC3 values is 0.147. Thus the 95% confidence limits (2xSD) for LLNA EC3 values 
      are within a factor of 2, comparable to those for physico-chemical measurements 
      such as partition coefficients and solubility. The residual SDs of Quantitative 
      Mechanistic Models (QMMs) based on physical organic chemistry parameters are 
      similar to the overall SD of the LLNA, indicating that QMMs of this type are 
      unlikely to be bettered for predictive accuracy.
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 - Api, Anne Marie
AU  - Api AM
AD  - Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff 
      Lake, NJ 07677, United States.
FAU - Aptula, Aynur O
AU  - Aptula AO
AD  - Unilever Safety and Environmental Assurance Centre, Colworth Science Park, 
      Sharnbrook, Bedford, MK44 1LQ, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160726
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  - 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  - Biological variability
OT  - LLNA
OT  - Non-animal prediction
OT  - QMM
EDAT- 2016/07/30 06:00
MHDA- 2017/03/10 06:00
CRDT- 2016/07/30 06:00
PHST- 2016/05/26 00:00 [received]
PHST- 2016/07/19 00:00 [revised]
PHST- 2016/07/21 00:00 [accepted]
PHST- 2016/07/30 06:00 [entrez]
PHST- 2016/07/30 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
AID - S0273-2300(16)30196-9 [pii]
AID - 10.1016/j.yrtph.2016.07.013 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2016 Oct;80:255-9. doi: 10.1016/j.yrtph.2016.07.013. 
      Epub 2016 Jul 26.