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Imprint
Hepatotoxic combination effects of food contaminants and active substances of pesticides
Project
Project code: BfR-SiP-08-1322-657
Contract period: 01.01.2016
- 31.12.2018
Purpose of research: Applied research
Consumers are exposed to complex mixtures of food ingredients, contaminants and/or active substances of pesticides. However, toxicological testing is performed for individual substances. This results in the need to develop methods for toxicological testing of mixtures. For the present project pesticides from the group of azoles and food ingredients from the group of polycyclic aromatic hydrocarbons (PAHs) were selected as test substances. The effects of some representatives of these classes of compounds are already well studied for the single substances. Many of the hepatotoxic effects of both classes of substances can be attributed to the activation of certain nuclear receptor pathways (CAR, PXR, AhR, PPAR, FXR). It is, however, still unknown to which extend these pathways interact after combined exposure to several of these substances and whether or not the combination results in increased (additive or synergistic) or decreased (antagonistic) effects. Within the framework of the proposed project, known hepatotoxic endpoints of the test substances such as apoptosis / necrosis, steatosis, changes in gene expression and receptor activation are considered in vitro. Both the hepatotoxic effects of individual test substances as well as combinations are analyzed and if available compared to existing in vivo data from literature or own previous work. In this way, the predictive quality of in vitro investigations for the assessment of combination effects of those substances on the liver should be improved and the relevance of the consideration of combination effects for risk assessment should be discussed. In the third year of the project, the in vitro results will be verified in vivo.
Section overview
Subjects
- Toxicology
