The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC50) with human and animal data showed a superior correlation with human DSA05 (μg/cm(2)) data (Spearman r=0.8500; P value (two-tailed)=0.0061) compared to LLNA data (Spearman r=0.5968; P value (two-tailed)=0.0542). DSA05=induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA05 data (Spearman r=0.8333; P value (two-tailed)=0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model.

An epidermal equivalent assay for identification and ranking potency of contact sensitizers / S. Gibbs, E. Corsini, S.W. Spiekstra, V. Galbiati, H.W. Fuchs, G. Degeorge, M. Troese, P. Hayden, W. Deng, E. Roggen. - In: TOXICOLOGY AND APPLIED PHARMACOLOGY. - ISSN 0041-008X. - 272:2(2013 Oct 15), pp. 529-541.

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

E. Corsini;V. Galbiati;
2013-10-15

Abstract

The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC50) with human and animal data showed a superior correlation with human DSA05 (μg/cm(2)) data (Spearman r=0.8500; P value (two-tailed)=0.0061) compared to LLNA data (Spearman r=0.5968; P value (two-tailed)=0.0542). DSA05=induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA05 data (Spearman r=0.8333; P value (two-tailed)=0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model.
Epidermal equivalent; IL-18; In vitro; Irritant; Potency; Sensitizer
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/231877
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