title: Data integration of non-animal tests for the development of a test battery to predict the skin sensitizing potential and potency of chemicals.
abstract: Recent changes in regulatory restrictions and social views against animal testing have accelerated development of reliable alternative tests for predicting skin sensitizing potential and potency of many chemicals. Lately, a test battery integrated with different in vitro tests has been suggested as a better approach than just one in vitro test for replacing animal tests. In this study, we created a dataset of 101 test chemicals with LLNA, human cell line activation test (h-CLAT), direct peptide reactivity assay (DPRA) and in silico prediction system. The results of these tests were converted into scores of 0-2 and the sum of individual scores provided the accuracy of 85% and 71% for the potential and potency prediction, compared with LLNA. Likewise, the straightforward tiered system of h-CLAT and DPRA provided the accuracy of 86% and 73%. Additionally, the tiered system showed a higher sensitivity (96%) compared with h-CLAT alone, indicating that sensitizers would be detected with higher reliability in the tiered system. Our data not only demonstrates that h-CLAT can be part of a test battery with other methods but also supports the practical utility of a tiered system when h-CLAT and DPRA are the first screening methods for skin sensitization.
authors.affiliation: Safety Science Research Laboratories, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi 321-3497, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nukada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Saitou
authors.initials: S
authors.lastname: Kazutoshi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishiyama
mesh_terms: D000485:Allergens / Q000009:adverse effects*; D000826:Animal Testing Alternatives / Q000379:methods; D051940:B7-2 Antigen / Q000276:immunology; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D064420:Drug-Related Side Effects and Adverse Reactions; D006241:Haptens / Q000009:adverse effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008239:Lysine / Q000737:chemistry; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009842:Oligopeptides / Q000737:chemistry; D011237:Predictive Value of Tests; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000485:Allergens; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006241:Haptens; D009842:Oligopeptides; D018799:Intercellular Adhesion Molecule-1; D008239:Lysine; D003545:Cysteine