Predicting skin sensitisation using a decision tree integrated testing strategy with an in silico model and in chemico/in vitro assays
| Autor: | Steven J. Canipa, Donna S. Macmillan, Martyn L. Chilton, Barber Christopher Gordon, Richard V. Williams |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Databases Factual Integration testing Computer science In silico Knowledge Bases Decision tree Nanotechnology Computational biology 010501 environmental sciences Toxicology Animal Testing Alternatives 01 natural sciences Workflow 03 medical and health sciences Structure-Activity Relationship Animals Humans Computer Simulation 0105 earth and related environmental sciences Skin fungi Decision Trees In vitro toxicology Reproducibility of Results General Medicine Skin Irritancy Tests 030104 developmental biology Dermatitis Allergic Contact Irritants Dermatitis Irritant Software Applicability domain |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 76 |
| ISSN: | 1096-0295 |
| Popis: | There is a pressing need for non-animal methods to predict skin sensitisation potential and a number of in chemico and in vitro assays have been designed with this in mind. However, some compounds can fall outside the applicability domain of these in chemico/in vitro assays and may not be predicted accurately. Rule-based in silico models such as Derek Nexus are expert-derived from animal and/or human data and the mechanism-based alert domain can take a number of factors into account (e.g. abiotic/biotic activation). Therefore, Derek Nexus may be able to predict for compounds outside the applicability domain of in chemico/in vitro assays. To this end, an integrated testing strategy (ITS) decision tree using Derek Nexus and a maximum of two assays (from DPRA, KeratinoSens, LuSens, h-CLAT and U-SENS) was developed. Generally, the decision tree improved upon other ITS evaluated in this study with positive and negative predictivity calculated as 86% and 81%, respectively. Our results demonstrate that an ITS using an in silico model such as Derek Nexus with a maximum of two in chemico/in vitro assays can predict the sensitising potential of a number of chemicals, including those outside the applicability domain of existing non-animal assays. |
| Databáze: | OpenAIRE |
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