PMID- 26251951
OWN - NLM
STAT- MEDLINE
DCOM- 20161223
LR  - 20161230
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 36
IP  - 5
DP  - 2016 May
TI  - An in vitro human skin test for assessing sensitization potential.
PG  - 669-84
LID - 10.1002/jat.3197 [doi]
AB  - Sensitization to chemicals resulting in an allergy is an important health issue. 
      The current gold-standard method for identification and characterization of 
      skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, 
      for a number of reasons there has been an increasing imperative to develop 
      alternative approaches to hazard identification that do not require the use of 
      animals. Here we describe a human in-vitro skin explant test for identification 
      of sensitization hazards and the assessment of relative skin sensitizing potency. 
      This method measures histological damage in human skin as a readout of the immune 
      response induced by the test material. Using this approach we have measured 
      responses to 44 chemicals including skin sensitizers, pre/pro-haptens, 
      respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and 
      previously misclassified compounds. Based on comparisons with the LLNA, the skin 
      explant test gave 95% specificity, 95% sensitivity, 95% concordance with a 
      correlation coefficient of 0.9. The same specificity and sensitivity were 
      achieved for comparison of results with published human sensitization data with a 
      correlation coefficient of 0.91. The test also successfully identified nickel 
      sulphate as a human skin sensitizer, which was misclassified as negative in the 
      LLNA. In addition, sensitizers and non-sensitizers identified as positive or 
      negative by the skin explant test have induced high/low T cell proliferation and 
      IFNgamma production, respectively. Collectively, the data suggests the human in-vitro 
      skin explant test could provide the basis for a novel approach for 
      characterization of the sensitizing activity as a first step in the risk 
      assessment process.
CI  - Copyright (c) 2015 John Wiley & Sons, Ltd.
FAU - Ahmed, S S
AU  - Ahmed SS
AUID- ORCID: 0000-0002-9213-0712
AD  - Alcyomics Ltd, Bulman House, Regent Centre, Gosforth, Newcastle-upon-Tyne, NE3 
      3LS, UK.
FAU - Wang, X N
AU  - Wang XN
AD  - Haematological Sciences, Institute of Cellular Medicine, Newcastle University, 
      Newcastle-upon-Tyne, NE2 4HH, UK.
FAU - Fielding, M
AU  - Fielding M
AD  - Haematological Sciences, Institute of Cellular Medicine, Newcastle University, 
      Newcastle-upon-Tyne, NE2 4HH, UK.
FAU - Kerry, A
AU  - Kerry A
AD  - Haematological Sciences, Institute of Cellular Medicine, Newcastle University, 
      Newcastle-upon-Tyne, NE2 4HH, UK.
FAU - Dickinson, I
AU  - Dickinson I
AD  - Haematological Sciences, Institute of Cellular Medicine, Newcastle University, 
      Newcastle-upon-Tyne, NE2 4HH, UK.
FAU - Munuswamy, R
AU  - Munuswamy R
AD  - Haematological Sciences, Institute of Cellular Medicine, Newcastle University, 
      Newcastle-upon-Tyne, NE2 4HH, UK.
FAU - Kimber, I
AU  - Kimber I
AD  - Faculty of Life Sciences, University of Manchester, Manchester, UK.
FAU - Dickinson, A M
AU  - Dickinson AM
AD  - Alcyomics Ltd, Bulman House, Regent Centre, Gosforth, Newcastle-upon-Tyne, NE3 
      3LS, UK.
AD  - Haematological Sciences, Institute of Cellular Medicine, Newcastle University, 
      Newcastle-upon-Tyne, NE2 4HH, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150807
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Allergens)
RN  - 0 (Haptens)
RN  - 0 (Irritants)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Allergens/*toxicity
MH  - *Animal Testing Alternatives
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Haptens/*toxicity
MH  - Humans
MH  - In Vitro Techniques
MH  - Interferon-gamma/metabolism
MH  - Irritants/*toxicity
MH  - Leukocytes, Mononuclear/cytology/drug effects/metabolism
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Risk Assessment
MH  - Sensitivity and Specificity
MH  - Skin/drug effects
MH  - *Skin Tests
MH  - T-Lymphocytes/drug effects/metabolism
OTO - NOTNLM
OT  - T-cell proliferation
OT  - antigen-specific priming
OT  - in vitro alternative to animal testing
OT  - interferon-gamma
OT  - local lymph node assay
OT  - potency
OT  - skin sensitization
EDAT- 2015/08/08 06:00
MHDA- 2016/12/24 06:00
CRDT- 2015/08/08 06:00
PHST- 2015/04/07 00:00 [received]
PHST- 2015/05/07 00:00 [revised]
PHST- 2015/05/22 00:00 [accepted]
PHST- 2015/08/08 06:00 [entrez]
PHST- 2015/08/08 06:00 [pubmed]
PHST- 2016/12/24 06:00 [medline]
AID - 10.1002/jat.3197 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2016 May;36(5):669-84. doi: 10.1002/jat.3197. Epub 2015 Aug 7.