Document Detail

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.
MedLine Citation:
PMID:  21751775     Owner:  NLM     Status:  Publisher    
Due to regulatory constraints and ethical considerations, research on alternatives to animal testing to predict the skin sensitization potential of novel chemicals has gained a high priority. Ideally, these alternatives should predict not only 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. It has thus been proposed to perform potency estimations within specific structural classes. 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 (ARE). A strong correlation between the EC3 values in the 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 an error of 1.4- and 2.6-fold. However, the LLNA EC3 values of two structurally different bifunctional monomers were overpredicted based on this dataset, indicating that accurate potency estimation by read-across based on in vitro data might be restricted to a relatively narrow applicability domain.
Tamara Delaine; Ida B Niklasson; Roger Emter; Kristina Luthman; Ann-Therese Karlberg; Andreas Natsch
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-13
Journal Detail:
Title:  Chemical research in toxicology     Volume:  -     ISSN:  1520-5010     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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