ToxPredict project launched: predicting liver toxicity and reducing animal testing

Before new active substances are authorised, they must undergo various pre-clinical tests. These tests assess whether they are carcinogenic, cause harm to embryos or induce genetic mutations, and also determine the dosage at which harm may occur. However, some of these substances subsequently fail in human trials after years of research, often because animal testing does not always reliably predict liver toxicity in humans. Against this background, the recently launched ToxPredict project has set itself two objectives: firstly, to develop an alternative method using human cells that delivers more reliable results; and secondly, to reduce the need for animal testing through this alternative approach.

Three research teams from the Leibniz Institute for Work Research (IfADo), Dortmund Technical University and Saarland University are developing such an alternative. It involves a combined testing method using human cells and computer models. The method utilises human liver cells derived from pluripotent stem cells – so-called hepatocyte-like cells (HLCs). These cells are optimised to become increasingly similar to real liver cells. The HLCs are then tested against a total of 104 known substances whose effects on humans are already understood. At the same time, a computer model is used to derive human blood concentrations and dosages from the laboratory results. This makes it possible to predict whether a substance will cause liver damage at a specific dose.

The advantages are clear: unlike primary liver cells, which must be obtained from donor livers and are extremely expensive, stem cells are available in unlimited quantities. Furthermore, the animal tests previously required under regulatory guidelines can be replaced, and the use of human cells yields more realistic results.

It must be noted, however, that whilst this alternative method identifies risks, it cannot prove absolute safety. Further testing is therefore necessary. Moreover, the method does not completely replace animal testing, but helps to reduce it in a targeted manner: for example, animal testing in accordance with OECD Guidelines 407, 408 or 409.

ToxPredict combines modern stem cell research, computer models and practical application. In this project, teams led by Prof. Jan Hengstler (TU Dortmund/IfADo), Dr Cristina Cadenas (IfADo) and Prof. Jörn Walter (Saarland University) are working together over a period of three years to develop this alternative method.

With funding of 851,700 euros from the Federal Ministry of Research, Technology and Space (BMFTR), this project aims to contribute to 3R research: the 3R principle stands for Replace, Reduce, Refine and aims to reduce animal testing as far as possible and to produce better predictions for humans.

The IfADo supports the ‘Transparent Animal Testing Initiative’ and ‘Understanding Animal Testing – A Scientific Information Initiative’.

This news article was created with the assistance of artificial intelligence and has been carefully checked and revised by the editorial team and the appropriate scientific experts. AI-generated images are identified as such.