title: Assessment of the skin irritation potential of chemicals by using the SkinEthic reconstructed human epidermal model and the common skin irritation protocol evaluated in the ECVAM skin irritation validation study.
abstract: Currently, two reconstructed human skin models, EpiDerm and EPISKIN are being evaluated in an ECVAM skin irritation validation study. A common skin irritation protocol has been developed, differing only in minor technical details for the two models. A small-scale study, applying this common skin irritation protocol to the SkinEthic reconstructed human epidermis (RHE), was performed at ZEBET at the BfR, Berlin, Germany, to consider whether this protocol could be successfully transferred to another epidermal model. Twenty substances from Phase III of the ECVAM prevalidation study on skin irritation were tested with the SkinEthic RHE. After minor, model-specific adaptations for the SkinEthic RHE, almost identical results to those obtained with the EpiDerm and EPISKIN models were achieved. The overall accuracy of the method was more than 80%, indicating a reliable prediction of the skin irritation potential of the tested chemicals when compared to in vivo rabbit data. As a next step, inter laboratory reproducibility was assessed in a study conducted between ZEBET and the Department of Experimental Toxicology, Schering AG, Berlin, Germany. Six coded substances were tested in both laboratories, with three different batches of the SkinEthic model. The assay results showed good reproducibility and correct predictions of the skin irritation potential for all six test chemicals. The results obtained with the SkinEthic RHE and the common protocol were reproducible in both phases, and the overall outcome is very similar to that of earlier studies with the EPISKIN and EpiDerm models. Therefore, the SkinEthic skin irritation assay test protocol can now be evaluated in a formal "catch-up" validation study.
authors.affiliation: ZEBET, National Centre for the Documentation and Evaluation of Alternative Methods to Animal Experiments, Federal Institute for Risk assessment (BfR), Diedersdorfer Weg 1, D-12277 Berlin, Germany. kandarova@centrum.sk
authors.forename: Helena
authors.initials: H
authors.lastname: Kandárová
authors.forename: Manfred
authors.initials: M
authors.lastname: Liebsch
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schmidt
authors.forename: Elke
authors.initials: E
authors.lastname: Genschow
authors.forename: Dieter
authors.initials: D
authors.lastname: Traue
authors.forename: Horst
authors.initials: H
authors.lastname: Spielmann
authors.forename: Kirstin
authors.initials: K
authors.lastname: Meyer
authors.forename: Claudia
authors.initials: C
authors.lastname: Steinhoff
authors.forename: Carine
authors.initials: C
authors.lastname: Tornier
authors.forename: Bart
authors.initials: B
authors.lastname: De Wever
authors.forename: Martin
authors.initials: M
authors.lastname: Rosdy
mesh_terms: D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects*; D005069:Evaluation Studies as Topic; D015386:Hazardous Substances / Q000145:classification / Q000633:toxicity*; D006801:Humans; D007509:Irritants / Q000145:classification / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D015386:Hazardous Substances; D007509:Irritants