期刊
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
卷 29, 期 4, 页码 373-388出版社
SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
DOI: 10.14573/altex.2012.4.373
关键词
risk assessment; animal-free methods; Tox21; artificial tissue; systems toxicology
资金
- Doerenkamp-Zbinden Foundation
- EU FP7 program (ESNATS)
- EU FP7 FETopen program The body on a chip [296257]
- L'Oreal
- COSMOS consortium (EU FP7 and Cosmetics Europe) [266835]
- US National Institute of General Medical Sciences (NIGMS)
- Medical Advances without Animals Trust (MAWA)
Several alternative methods to replace animal experiments have been accepted by legal bodies. An even larger number of tests are under development or already in use for non-regulatory applications or for the generation of information stored in proprietary knowledge bases. The next step for the use of the different in vitro methods is their combination into integrated testing strategies (ITS) to get closer to the overall goal of predictive in vitro-based risk evaluation processes. We introduce here a conceptual framework as the basis for future ITS and their use for risk evaluation without animal experiments. The framework allows incorporation of both individual tests and already integrated approaches. Illustrative examples for elements to be incorporated are drawn from the session Innovative technologies at the 8th World Congress on Alternatives and Animal Use in the Life Sciences, held in Montreal, 2011. For instance, LUHMES cells (conditionally immortalized human neurons) were presented as an example for a 2D cell system. The novel 3D platform developed by InSphero was chosen as an example for the design and use of scaffold-free, organotypic microtissues. The identification of critical pathways of toxicity (PoT) may be facilitated by approaches exemplified by the MatTek 3D model for human epithelial tissues with engineered toxicological reporter functions. The important role of in silico methods and of modeling based on various pre-existing data is demonstrated by Altamira's comprehensive approach to predicting a molecule's potential for skin irritancy. A final example demonstrates how natural variation in human genetics may be overcome using data analytic (pattern recognition) techniques borrowed from computer science and statistics. The overall hazard and risk assessment strategy integrating these different examples has been compiled in a graphical work flow.
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