PMID- 22728231
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20141120
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 27
IP  - 3
DP  - 2013 Apr
TI  - Transfer of a two-tiered keratinocyte assay: IL-18 production by NCTC2544 to 
      determine the skin sensitizing capacity and epidermal equivalent assay to 
      determine sensitizer potency.
PG  - 1135-50
LID - S0887-2333(12)00154-3 [pii]
LID - 10.1016/j.tiv.2012.06.004 [doi]
AB  - At present, the identification of potentially sensitizing chemicals is carried 
      out using animal models. However, it is very important from ethical, safety and 
      economic point of view to have biological markers to discriminate allergy and 
      irritation events, and to be able to classify sensitizers according to their 
      potency, without the use of animals. Within the Sens-it-iv EU Frame Programme 6 
      funded Integrated Project (LSHB-CT-2005-018681), a number of in vitro, human cell 
      based assays were developed which, when optimized and used in an integrated 
      testing strategy, may be able to distinguish sensitizers from non-sensitizers. 
      This study describes two of these assays, which when used in a tiered strategy, 
      may be able to identify contact sensitizers and also to quantify sensitizer 
      potency. Tier 1 is the human keratinocyte NCTC2544 IL-18 assay and tier 2 is the 
      Epidermal Equivalent potency assay. The aim of this study is to show the 
      transferability of the two-tiered approach with training chemicals: 3 sensitizers 
      (DNCB, resorcinol, pPD) and 1 non sensitizer (lactic acid) in tier 1 and 2 
      sensitizers with different potency in tier 2 (DNCB; extreme and resorcinol; 
      moderate). The chemicals were tested in a non-coded fashion. Here we describe the 
      transferability to naive laboratories, the establishment of the standard 
      operating procedure, critical points, acceptance criteria and project management. 
      Both assays were successfully transferred to laboratories that had not performed 
      the assays previously. The two tiered approach may offer an unique opportunity to 
      provide an alternative method to the Local Lymph Node Assay (LLNA). These assays 
      are both based on the use of human keratinocytes, which have been shown over the 
      last two decades, to play a key role in all phases of skin sensitization.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Teunis, Marc
AU  - Teunis M
AD  - University of Applied Sciences, Utrecht, The Netherlands. marc.teunis@hu.nl
FAU - Corsini, Emanuela
AU  - Corsini E
FAU - Smits, Mieke
AU  - Smits M
FAU - Madsen, Charlotte Bernhard
AU  - Madsen CB
FAU - Eltze, Tobias
AU  - Eltze T
FAU - Ezendam, Janine
AU  - Ezendam J
FAU - Galbiati, Valentina
AU  - Galbiati V
FAU - Gremmer, Eric
AU  - Gremmer E
FAU - Krul, Cyrille
AU  - Krul C
FAU - Landin, Annette
AU  - Landin A
FAU - Landsiedel, Robert
AU  - Landsiedel R
FAU - Pieters, Raymond
AU  - Pieters R
FAU - Rasmussen, Tina Frid
AU  - Rasmussen TF
FAU - Reinders, Judith
AU  - Reinders J
FAU - Roggen, Erwin
AU  - Roggen E
FAU - Spiekstra, Sander
AU  - Spiekstra S
FAU - Gibbs, Susan
AU  - Gibbs S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120619
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Allergens)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Allergens/*toxicity
MH  - *Biological Assay
MH  - Cell Line
MH  - Cell Survival
MH  - Dermatitis, Allergic Contact/etiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-18/*metabolism
MH  - Keratinocytes/*drug effects/metabolism
MH  - Reproducibility of Results
EDAT- 2012/06/26 06:00
MHDA- 2013/09/21 06:00
CRDT- 2012/06/26 06:00
PHST- 2012/01/18 00:00 [received]
PHST- 2012/05/31 00:00 [revised]
PHST- 2012/06/13 00:00 [accepted]
PHST- 2012/06/26 06:00 [entrez]
PHST- 2012/06/26 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - S0887-2333(12)00154-3 [pii]
AID - 10.1016/j.tiv.2012.06.004 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2013 Apr;27(3):1135-50. doi: 10.1016/j.tiv.2012.06.004. Epub 
      2012 Jun 19.