title: Two novel prediction models improve predictions of skin corrosive sub-categories by test methods of OECD Test Guideline No. 431.
abstract: Alternative test methods often use prediction models (PMs) for converting endpoint measurements into predictions. Two PMs are used for the skin corrosion tests (SCTs) of the OECD Test Guideline No. 431 (TG 431). One is specific to EpiSkin™ test method, whereas EpiDerm™, SkinEthic™ RHE and epiCS® share a common PM. These methods are based on reconstructed human epidermis models wherein cell viability values are measured. Their PMs allow translating those values into sub-categories of corrosive chemicals, Category 1A (Cat1A) and a combination of Categories 1B/1C (Cat1BC), and identifying non-corrosive (NC) chemicals. EpiSkin™'s PM already results in sufficiently accurate predictions. The common PM of the three others accurately identifies all corrosive chemicals but, for sub-categorization, an important fraction of Cat1BC chemicals (40-50%) is over-predicted as Cat1A. This paper presents a post-hoc analysis of validation data on a set of n=80 chemicals. It investigates: why this common PM causes these over-predictions and how two novel PMs that we developed (PMvar1 and PMvar2) improve the predictive capacity of these methods. PMvar1 is based on a two-step approach; PMvar2 is based on a single composite indicator of cell viability. Both showed a greater capacity to predict Cat1BC, while Cat1A correct predictions remaining at least at the same level of EpiSkin™. We suggest revising TG 431, to include the novel PMs in view of improving the predictive capacity of its SCTs.
authors: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Systems Toxicology Unit, European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Via E. Fermi 2749, Ispra, Italy. Electronic address: bertrand.desprez@ec.europa.eu.
authors: Bertrand
authors: B
authors: Desprez
authors: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Systems Toxicology Unit, European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Via E. Fermi 2749, Ispra, Italy.
authors: João
authors: J
authors: Barroso
authors: European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection (IHCP), Systems Toxicology Unit, European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), Via E. Fermi 2749, Ispra, Italy.
authors: Claudius
authors: C
authors: Griesinger
authors: MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia.
authors: Helena
authors: H
authors: Kandárová
authors: L'Oréal Research & Innovation, Aulnay Sous-Bois, France.
authors: Nathalie
authors: N
authors: Alépée
authors: CellSystems® Biotechnologie Vertrieb GmbH, Troisdorf, Germany.
authors: Horst W
authors: HW
authors: Fuchs
mesh_terms: D000826:Animal Testing Alternatives; D002424:Caustics / Q000633:toxicity*; D004817:Epidermis / Q000473:pathology; D017408:Guidelines as Topic; D006801:Humans; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology; D023422:Skin Irritancy Tests / Q000379:methods* / Q000592:standards; D018675:Toxicity Tests / Q000592:standards*
chemical_list: D002424:Caustics
keywords: OECD; Prediction model; Skin corrosion; Sub-categorization; UN GHS