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Non-animal Methods for Toxicity Testing

Cell-based Technologies

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Cultured animal and human cells have been used in research for decades. Cultured cells are also commonly used in toxicology experiments to identify the biological effects of chemicals and drugs (mechanisms of action) and in screening assays to determine the relative toxicity of substances. The goal of in vitro toxicology is to develop a range of cellular to organotypic models capable of replacing animals in toxicity tests. Since tests on whole animals involve significant biological complexity, many in vitro models and assay endpoints will be needed to replicate the key human health endpoints assessed for each specific target system, for regulatory testing. Furthermore, methods such as growing cells as a single layer on plastic plates are usually insufficient for replicating the in vivo behavior and responses of cells and tissues. Therefore, efforts in cellular technologies are two-pronged, involving a) the development of 3-dimensional (3D) cellular/tissue models that replicate the in vivo tissue and b) the development of endpoints/assays to assess the toxicity response(s) of the in vitro model to the substance being tested. In some cases, in vitro methods will be part of a testing scheme integrated with other methods such as -omics (genomics, proteomics, metabolomics), (quantitative) structure activity relationship [(Q)SAR] analysis, biochemical pathway analysis, and decision support analysis. Eventually all of the information will be integrated and evaluated using a cell systems biology platform.

Background information on the following topics and more will be provided at this location of AltTox.org in the future; please check back again.

  • Retaining in vivo properties in vitro
  • Primary cells versus cell lines
  • The use of human cells
  • Developing tissues and organs for research and testing
  • Use of stem cells in tissue models
  • Biomarkers to indicate in vivo phenotype of cells
  • In vitro biomarkers of toxicity
  • Cells and the -omics technologies
  • New assay detection technologies
  • Developments in 3-D constructs
  • Microfluidic cell culture devices
  • Cell systems biology
  • Cell visualization technologies
  • ECVAM research programs: Predictomics; Sen-si-tiv; ReProTec; A-Cute-Tox