Binary test battery with KeratinoSens™ and h-CLAT as part of a bottom-up approach for skin sensitization hazard prediction
| Autor: | Yuki Otsubo, Masaaki Miyazawa, Taku Nishijo, Hideyuki Mizumachi, Kazutoshi Saito, Hitoshi Sakaguchi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Test battery Hazard (logic) Computer science Integration testing Binary number 010501 environmental sciences Hazard analysis Animal Testing Alternatives Toxicology computer.software_genre Sensitivity and Specificity 01 natural sciences Cell Line 03 medical and health sciences Animals Humans Skin 0105 earth and related environmental sciences Local lymph node assay Skin sensitization General Medicine Allergens Local Lymph Node Assay 030104 developmental biology Dermatitis Allergic Contact Data mining computer |
| Zdroj: | Regulatory Toxicology and Pharmacology. 88:118-124 |
| ISSN: | 0273-2300 |
| DOI: | 10.1016/j.yrtph.2017.06.002 |
| Popis: | Skin sensitization is one of the key safety endpoints for chemicals applied directly to the skin. Several integrated testing strategies (ITS) using multiple non-animal test methods have been developed to accurately evaluate the sensitizing potential of chemicals, but there is no regulatory-accepted ITS to classify a chemical as a non-sensitizer. In this study, the predictive performance of a binary test battery with KeratinoSens™ and h-CLAT compared to the local lymph node assay (LLNA) and human data was examined using comprehensive dataset of 203 chemicals. When two negative results indicate a non-sensitizer, the binary test battery provided sensitivity of 93.4% or 94.4% compared with the LLNA or human data. Taking into account the predictive limitations (i.e. high log Kow, pre-/pro-haptens and acyl transfer agents (or amine-reactive)), the binary test battery had extremely high sensitivity comparable to that of the 3 out of 3 ITS where three negative results of the DPRA, KeratinoSens™ and h-CLAT indicate a non-sensitizer. Therefore, the data from KeratinoSens™ or h-CLAT may provide partly redundant information on the molecular initiating event derived from DPRA. Taken together, the binary test battery of KeratinoSens™ and h-CLAT could be used as part of a bottom-up approach for skin sensitization hazard prediction. |
| Databáze: | OpenAIRE |
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