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2014
Journal Article
Titel
Toxicological databases: Modern tools to reduce, refine and replace animal testing
Abstract
Implementation of the 3R principles (Reduction, Refinement and Replacement of animal testing) in hazard and risk assessment is a prior goal in several regulations, e.g. REACh. Read across, applying QSAR models, integrated test strategies or grouping approaches are very valuable tools to achieve this goal. All these tools demand systematic and structured analyses of available data which can easily be performed with high quality relational databases containing all relevant parameters for analyzing: structural data, data on study design, and toxicological endpoints. Current major concerns are complex toxicological studies such as long term repeated dose studies or studies on reproductive toxicity and toxicological studies on nanomaterials that are time and costs intensive and require the testing of numerous animals. For efficiently analyzing the available data, Fraunhofer ITEM developed three relational databases each with special focus on repeated dose toxicity (RepDose), fertility and developmental toxicity (FeDTex), both sponsored by CEFIC LRI and particle and fiber toxicity (PaFtox). RepDose contains currently about 3000 studies with 800 chemicals in rodents, FeDTex 535 studies with 269 chemicals in rodents and rabbits and PaFtox 131 studies in rodents with 17 different materials (65 different (nano)materials based on primary size or 87 different materials based on primary and secondary size). These databases can be used as stand-alone or in combination linked by the Fraunhofer Toxtool (FTT), an overarching database. The databases have been or are currently used to address the following issues: 1) Development of an integrated testing strategy (ITS) for repeated dose toxicity. This ITS evaluates under which conditions high quality old studies can still be used for regulatory risk assessment. (OSIRIS). 2) Derivation of reliable factors used for time extrapolations or route to route extrapolations (ERASM). 3) Use of existing animal data to develop integrated test strategies by identifying critical targets and by validation of alternative methods covering diverse adverse outcome pathways ((OSIRIS, ChemScreen, AIMT2, Detective, Exitox). 4) Evaluation of the predictive power of RepDose studies for reproductive toxicity (ChemScreen). 5) Grouping approaches for nanomaterials (ongoing research) 6) Identification of structural alerts for endocrine properties of chemicals (ChemScreen)