PMID- 21751775
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20151119
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 24
IP  - 8
DP  - 2011 Aug 15
TI  - Structure--activity relationship between the in vivo skin sensitizing potency of 
      analogues of phenyl glycidyl ether and the induction of Nrf2-dependent luciferase 
      activity in the KeratinoSens in vitro assay.
PG  - 1312-8
LID - 10.1021/tx200196s [doi]
AB  - Because of regulatory constraints and ethical considerations, research on 
      alternatives to animal testing to predict the skin sensitization potential of 
      novel chemicals has become a high priority. Ideally, these alternatives should 
      not only predict the hazard of novel chemicals but also rate the potency of skin 
      sensitizers. Currently, no alternative method gives reliable potency estimations 
      for a wide range of chemicals in differing structural classes. Performing potency 
      estimations within specific structural classes has thus been proposed. Detailed 
      structure-activity studies for the in vivo sensitization capacity of a series of 
      analogues of phenyl glycidyl ether (PGE) were recently published. These studies 
      are part of an investigation regarding the allergenic activity of epoxy-resin 
      monomers. Here we report data on the same chemicals in the KeratinoSens in vitro 
      assay, which is based on a stable transgenic keratinocyte cell line with a 
      luciferase gene under the control of an antioxidant response element. A strong 
      correlation between the EC3 values in the local lymph node assay (LLNA) and both 
      the luciferase-inducing concentrations and the cytotoxicity in the cell-based 
      assay was established for six analogues of PGE. This correlation allowed the 
      potency in the LLNA of two novel structurally closely related derivatives to be 
      predicted by read-across with errors of 1.4- and 2.6-fold. However, the LLNA EC3 
      values of two structurally different bifunctional monomers were overpredicted on 
      the basis of this data set, indicating that accurate potency estimation by 
      read-across based on in vitro data might be restricted to a relatively narrow 
      applicability domain.
FAU - Delaine, Tamara
AU  - Delaine T
AD  - Department of Chemistry, Dermatochemistry and Skin Allergy, University of 
      Gothenburg , SE-412 96 Gothenburg, Sweden.
FAU - Niklasson, Ida B
AU  - Niklasson IB
FAU - Emter, Roger
AU  - Emter R
FAU - Luthman, Kristina
AU  - Luthman K
FAU - Karlberg, Ann-Therese
AU  - Karlberg AT
FAU - Natsch, Andreas
AU  - Natsch A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110722
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Phenyl Ethers)
RN  - 44KJQ1655I (phenylglycidyl ether)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Keratinocytes/*drug effects
MH  - Local Lymph Node Assay
MH  - Luciferases/genetics/*metabolism
MH  - Mice
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Phenyl Ethers/*chemistry/toxicity
MH  - Structure-Activity Relationship
EDAT- 2011/07/15 06:00
MHDA- 2011/12/14 06:00
CRDT- 2011/07/15 06:00
PHST- 2011/07/15 06:00 [entrez]
PHST- 2011/07/15 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
AID - 10.1021/tx200196s [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2011 Aug 15;24(8):1312-8. doi: 10.1021/tx200196s. Epub 2011 Jul 
      22.