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

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• 作者：Susan Gibbs ; Emanuela Corsini ; S ; er W. Spiekstra ; Valentina Galbiati ; Horst W. Fuchs ; George DeGeorge ; Matthew Troese ; Patrick Hayden ; Wei Deng ; Erwin Roggen
• 关键词：CA ; cinnamaldehyde ; C-OH ; cinnamic alcohol ; DiSFeB ; Dipartimento di Scienze Farmacologiche e Biomolecolari ; DNCB ; dinitrochlorobenzene ; DMF ; dimethylformamide ; DMSO ; dimethylsulfoxide ; DSA05 (¦Ìg/cm2) ; induction dose per skin area (DSA) that produces a po
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2013
• 出版时间：15 October, 2013
• 年：2013
• 卷：272
• 期：2
• 页码：529-541
• 全文大小：1396 K

文摘

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 24 h 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 (¦Ìg/cm²) 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.