WFRF:(Luthman Kristina)
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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.
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- Delaine, Tamara, 1981 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry
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- Niklasson, Ida B, 1982 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi,Department of Chemistry
- Emter, Roger (författare)
- visa fler...
- Natsch, Andreas (författare)
- visa färre...
- (creator_code:org_t)
- 2011-07-22
- 2011
- Engelska.
- Ingår i: Chemical research in toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 24:8, s. 1312-8
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
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