A strategy for safety assessment of chemicals with data gaps for developmental and/or reproductive toxicity
| Autor: | Kara E. Woeller, Sharon B. Stuard, Karen Blackburn, Joan Fisher, Jorge M. Naciff, George P. Daston, Echoleah S. Rufer, Cathy Lester |
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| Rok vydání: | 2015 |
| Předmět: |
Databases
Factual Computer science Decision tree Embryonic Development Toxicology computer.software_genre Risk Assessment Hazardous Substances Fetal Development Toxicity Tests Animals Humans Selection (genetic algorithm) computer.programming_language Alternative methods Dart Gap filling No-Observed-Adverse-Effect Level Reproduction Decision Trees Uncertainty General Medicine Tree (data structure) Teratogens Data mining Reproductive toxicity human activities computer Test data |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 72(2) |
| ISSN: | 1096-0295 |
| Popis: | Alternative methods for full replacement of in vivo tests for systemic endpoints are not yet available. Read across methods provide a means of maximizing utilization of existing data. A limitation for the use of read across methods is that they require analogs with test data. Repeat dose data are more frequently available than are developmental and/or reproductive toxicity (DART) studies. There is historical precedent for using repeat dose data in combination with a database uncertainty factor (UF) to account for missing DART data. We propose that use of the DART decision tree (Wu et al., 2013), in combination with a database UF, provides a path forward for DART data gap filling that better utilizes all of the data. Our hypothesis was that chemical structures identified by the DART tree as being related to structures with known DART toxicity would potentially have lower DART NOAELs compared to their respective repeat dose NOAELs than structures that lacked this association. Our analysis supports this hypothesis and as a result also supports that the DART decision tree can be used as part of weight of evidence in the selection of an appropriate DART database UF factor. |
| Databáze: | OpenAIRE |
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