Two Novel Prediction Models Improve Predictions of Skin Corrosive Sub-categories by Test Methods of OECD Test Guideline No. 431

Alternative test methods often use prediction models (PMs) for converting endpoint measurements into predictions. Two PMs are used in the OECD Test Guideline No. 431 (TG431) on skin corrosion. One is specific to EpiSkin™ test method, whereas EpiDerm™, SkinEthic™RHE and epiCS® share a common PM. These four methods are Reconstructed human Epidermis models wherein several 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 chemicals. EpiSkin™'s PM already results in sufficiently accurate predictions. The common PM of the three others accurately identifies all corrosive chemicals but, regarding their 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 consistent set of n=80 chemicals. It investigates (i) why this common PM causes these over-predictions and (ii) 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 marked greater capacity to predict Cat1BC, and Cat1A correct predictions remain at least at the same level of EpiSkin™. We suggest revising TG431, and its performance standards, to include the novel PMs in view of improving the predictive capacity of its in vitro skin corrosion methods.

DESPREZ Bertrand;  VIEGAS BARROSO Joao Filipe;  GRIESINGER Claudius;  KANDAROVA Helena;  ALEPEE Natalie;  FUCHS Horst; 

2016-01-19

PERGAMON-ELSEVIER SCIENCE LTD

JRC93343

0887-2333,   

http://www.sciencedirect.com/science/article/pii/S0887233315002106,    https://publications.jrc.ec.europa.eu/repository/handle/JRC93343,   

10.1016/j.tiv.2015.08.015,