TIMES-SS--a promising tool for the assessment of skin sensitization hazard. A characterization with respect to the OECD validation principles for (Q)SARs and an external evaluation for predictivity
| Autor: | Ovanes G. Mekenyan, Grace Patlewicz, Paul T. Bailey, Charlotte Bernhard Madsen, David W. Roberts, Eva Bay Wedebye, Petra S. Kern, Lawrence K. Low, S. Dimitrov, Jay Russell Niemelä, Mike I. H. Comber, Gergana Dimitrova, Aynur O. Aptula, Richard D. Phillips |
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| Rok vydání: | 2007 |
| Předmět: |
Hazard (logic)
Validation study Quantitative Structure-Activity Relationship Toxicology Machine learning computer.software_genre Animal Testing Alternatives Risk Assessment Mice media_common.cataloged_instance Medicine Animals Computer Simulation European Union European union Sensitization media_common Skin business.industry Local lymph node assay Skin sensitization General Medicine Local Lymph Node Assay Skin Irritancy Tests Expert system medicine.anatomical_structure Models Chemical Irritants Artificial intelligence business computer |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 48(2) |
| ISSN: | 0273-2300 |
| Popis: | The TImes MEtabolism Simulator platform used for predicting Skin Sensitization (TIMES-SS) is a hybrid expert system that was developed at Bourgas University using funding and data from a Consortium comprising industry and regulators. The model was developed with the aim of minimizing animal testing and to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs. Here, we describe the extent to which the five OECD principles are met and in particular the results from an external evaluation exercise that was recently carried out. As part of this exercise, data were generated for 40 new chemicals in the murine local lymph node assay (LLNA) and then compared with predictions made by TIMES-SS. The results were promising with an overall good concordance (83%) between experimental and predicted values. Further evaluation of these results highlighted certain inconsistencies which were rationalized by a consideration of reaction chemistry principles for sensitization. Improvements for TIMES-SS were proposed where appropriate. TIMES-SS is a promising tool to aid in the evaluation of skin sensitization hazard under legislative programs such as REACH. |
| Databáze: | OpenAIRE |
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