Category Research project
  • Toxikologie
  • Alternativmethoden zum Tierversuch

LivSys-Transfer – transfer of the LivSys in vitro system for hepatotoxicity into application

Project status
Completed
Project start
Jan 2017
Project end
Jan 2020
Acronym
LivSys-Transfer
Department
Lebensmittelsicherheit

Description and Objective

The LivSys-Transfer project has the specific goal of applying a promising new in vitro system for predicting the hepatotoxicity of chemicals. The basis is the results of the pilot phase of the project, where a signature of seven genes was already identified as a marker for the hepatotoxic effect of test chemicals in primary human hepatocytes in vitro and tested for their robustness in an interlaboratory comparison. The following goals were specifically pursued in the "LivSys-Transfer" project: 1.) Additional analyzes with the test substances already in use and with new, additional test substances should be used to further confirm the functionality of the in vitro system. This also included the implementation of a blinded study. 2.) In an optimization phase, further functional parameters should be examined and, if suitable, integrated into the test system. 3.) To simplify the use of the test system and to reduce costs, the test system should be transferred from primary human hepatocytes to human liver tumor cell lines. With the LivSys in vitro system, a cell culture-based test system is to be made available that enables the identification of hepatotoxic chemicals in human liver cells without animal testing and that is able to predict critical serum concentrations of the active substances and chemicals examined.

Result

The experiments carried out at the BfRshort forGerman Federal Institute for Risk Assessment were intended on the one hand to examine the suitability of the HepaRG cell line in connection with the 7-gene signature from the pilot phase of "LivSys" as an in vitro system for the detection of hepatotoxicity, on the other hand as part of a transfer to the application of food and exposureExposureTo glossary-relevant chemicals, which are currently the focus of toxicological risk assessment. An overall evaluation of the project results will be made at a later date with the final report of the IfADo as the coordinating institution, as soon as the sub-project there has been completed. The results obtained with the food contaminants indicate that the test system is suitable for detecting the hepatotoxicity of these substances. A future use of the test system from "LivSys-Transer" could be as a screening system for testing for hepatotoxicity in order to identify potentially liver-toxic and therefore toxicologically problematic chemicals in vitro. However, a final assessment of the system can only be made once all the sub-projects have been completed and the overall results are available.
Type of project

Third-party funded project

Research focus

Alternativmethoden zum Tierversuch

Organisational units and partners

Lead specialist group: Zellbasierte Teststrategien und Toxikogenomik (74)
Contact persons: Prof. Dr. Dr. Alfonso Lampen, Dr. Thorsten Buhrke
External partner: Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Universität Leipzig, Technische Universität Dortmund

Funding body and grant number

Bundesministerium für Bildung und Forschung
031L0119C

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