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Investigation of mixture effects of pesticides in vitro (Combiomics 2)

01/2017-12/2019

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

BMBF grant number: 031L0118A

Project homepage: -

Project description:

Consumers are exposed to residues of various pesticides via foodstuff. Due to the fact that the toxicological properties of pesticidal active substances are mostly assessed on a single-compound basis in animal experiments for regulatory purposes, data on possible combination effects are scarce. The investigation of combination effects, which is foreseen by the respective guidelines for evaluation and authorization of pesticidal active substances, thus poses a challenge to regulatory toxicology. The development of in vitro systems for the assessment of combination effects is of utmost importance, since the multitude of investigations cannot be performed in animals. During the first project phase combination effects of a group of fungicides (triazoles) were investigated. Several cell lines were screened for their suitability to analyze mixture effects using omics techniques. In the second phase of the project, successfully tested methods and cell lines will be validated in a standardized in vitro testing battery aimed to comply with future regulatory requirements.

BfR parts of the study:

The BfR will take over the coordination of the joint project. The planned in vitro examinations will be conducted at the BfR using the hepatic stem cell line HepaRG, and for validation purposes also on human hepatocytes. The cells will be incubated with various combinations of food-relevant pesticidal active substances. Subesequently, RNA and protein isolates are analysed by the project partners at the University of Bielefeld (transcriptomics) and NMI Reutlingen (proteomics) for the expression of the combination effect markers identified in the first project phase. The panel of identified markers is to be further optimised in the course of the project and the usability of the in vitro model system characterised for mixtures of various chemical classes of active pesticide substances.

Project partners:

• The Natural and Medical Sciences Institute at the University of Tübingen, Germany
• Bielefeld University, Germany

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