TIMES-SS--a mechanistic evaluation of an external validation study using reaction chemistry principles
| Autor: | Mike I. H. Comber, David W. Roberts, Ovanes G. Mekenyan, Petra S. Kern, Grace Patlewicz, Charlotte Bernhard Madsen, Lawrence K. Low, Jay Russell Niemelä, S. Dimitrov, Gergana Dimitrova, Paul T. Bailey, Eva Bay Wedebye, Richard D. Phillips, Aynur O. Aptula |
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| Rok vydání: | 2007 |
| Předmět: |
Quantitative Structure-Activity Relationship
Computational biology Carbamide Peroxide Acetates Toxicology Animal Testing Alternatives Toxicity Tests medicine Animals Urea Sensitization Molecular Structure Local lymph node assay Chemistry Skin sensitization External validation General Medicine Local Lymph Node Assay Skin Irritancy Tests Peroxides Allyl Compounds Drug Combinations medicine.anatomical_structure Chemical engineering Models Chemical Irritants |
| Zdroj: | Technical University of Denmark Orbit |
| ISSN: | 0893-228X |
| 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 comprised of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic three-dimensional quantitative structure-activity relationships. Here, we describe an external validation 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. The LLNA results were evaluated with respect to reaction chemistry principles for sensitization. Additional testing on a further four chemicals was carried out to explore some of the specific reaction chemistry findings in more detail. Improvements for TIMES-SS, where appropriate, were put forward together with proposals for further research work. TIMES-SS is a promising tool to aid in the evaluation of skin sensitization potential under legislative programs such as REACH. |
| Databáze: | OpenAIRE |
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