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Transfer of the LivSys in vitro system for hepatotoxicity into application (LivSys-Transfer)

02/2017-01/2020

This third-party funded project is conducted in the framework of the BfR research programme on alternatives to animal experiments.

BMBF grant number: 031L0119C

Project homepage: -

Project description:

Risk Assessment of toxic properties of chemicals and subsequent regulation by law is preliminarily based on data obtained from animal experiments. Due to ethical reasons, alternative methods are to be developed in order to reduce the number of animal experiments in the long term. In a pilot phase, a set of seven genes with altered gene expression in the presence of hepatotoxic substances was identified by using human liver cells. The aim of the project is to demonstrate the applicability of the 7-gene signature for the prediction of hepatotoxic effects of test substances by using cell culture models (“proof of principle”). A broad set of known hepatotoxic and non-hepatotoxic substances will be used to examine whether the prediction based on the 7-gene signature leads to correct positive and negative results respectively. Moreover, the data obtained from cell culture experiments will be correlated with known blood serum levels of the substances in order to employ computer models for the deviation of human-relevant hepatotoxic concentrations.

BfR parts of the project:

The LivSys transfer project is subdivided into six work packages (WP) in which the four project partners are involved to varying degrees. More confirmation analyses with the test substances of the LivSys pilot phase are scheduled in WP1. Additional positive and negative application-relevant substances are to be examined within the scope of WP2. An optimisation phase, in the course of which further functional parameters may be integrated into the LivSys test system, is illustrated by WP3. The functionality of the then optimised LivSys test system is to be checked in a blind study with a large number of other substances (WP4).  WP5 serves the further optimisation/simplification of the LivSys test system with regard to the use of permanent human hepatocyte cell lines instead of primary human hepatocytes and other modifications of the system with a view towards possible cost reduction. Finally, AP6 aims at the practical usability of the LivSys test system using the example of several food-relevant substances which are currently in the focus of risk assessment. BfR is involved in WP 4-6 in association with the other project partners.

Project partners:

• TU Dortmund University, Germany (coordination)
• Charité - Universitätsmedizin Berlin, Germany

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