03100nas a2200493   4500000000100000008004100001260001500042653002400057653002300081653002800104653002300132653002200155653002500177653003200202653003100234653002300265100002700288700002300315700002200338700001600360700001900376700001700395700001800412700001900430700002100449700002100470700001900491700001800510700001900528700001800547700003100565700001800596700002100614700002000635700002000655700001600675700001900691245009500710856005000805300001200855490000700867520171800874022001402592       2018                            d  c2018-05-2810aLLNA reference data10aSkin sensitization10aadverse outcome pathway10adefined approaches10ahazard assessment10ahuman reference data10aintegrated testing strategy10anew approach methodologies10apotency assessment1 aNicole C. Kleinstreuer1 aSebastian Hoffmann1 aNathalie Alépée1 aDavid Allen1 aTakao Ashikaga1 aWarren Casey1 aElodie Clouet1 aMagalie Cluzel1 aBertrand Desprez1 aNichola Gellatly1 aCarsten Göbel1 aPetra S. Kern1 aMartina Klaric1 aJochen Kühnl1 aSilvia Martinozzi-Teissier1 aKarsten Mewes1 aMasaaki Miyazawa1 aJudy Strickland1 aErwin van Vliet1 aQingda Zang1 aDirk Petersohn00aNon-animal methods to predict skin sensitization (II): an assessment of defined approaches  uhttps://doi.org/10.1080/10408444.2018.1429386  a359-3740 v483 aSkin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.  a1040-8444