4. Organ Toxicity

The major aim of this research line is to develop in vitro methods or short term in vivo methods for testing the organ toxic properties of compounds as an alternative to the chronic rodent toxicity assays for long term toxicity. Thereby the focus will be on two major target organs, namely the liver and the kidney, since in these organs organ-specific toxic effects are frequently observed in long-term rodent assays. Furthermore, in these organs unexpected toxicity is regularly observed in humans once a product has been put on the market. These idiosyncratic effects are a major reason to withdraw drugs from the market, having huge financial consequences.

The high attrition rate of compounds in in vivo toxicity testing following a positive evaluation in vitro tests demonstrates the need for improved model systems. To improve the predictability of in vitro tests, it is essential to more closely mimic the relevant organ targets of toxicants. Three dimensional (3D) cell cultures display an improved level of differentiation and develop structures absent in 2D cultures, and as a consequence are more consistent with the native organ.

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