Investigation of hepatotoxic and genotoxic potential as well as metabolism of food-relvant pyrrolizidine alkaloids (PA2)
This third-party funded project is conducted in the framework of the BfR research programme on modern methods in toxicology.
DFG grant number: TH1925/2-1
Project homepage: http://gepris.dfg.de/gepris/projekt/322267165?language=en
The findings of high pyrrolizidine alkaloid (PA) levels in tea and herbal infusions and other plant derived food have to be considered as a relevant topic in food safety, especially, as some of these toxins are classified as genotoxic carcinogens. The PAs detected in different types of tea and herbal infusions belonged to different structural types, as for instance open chained PA esters are mainly found in fennel infusions, while black tea was dominated by cyclic PA esters. More precisely, the PA levels determined in food are the sum of a large number of individual PAs that occur in parallel. As no substantial data on the relative toxicities of PAs are available, the total amounts of individual PAs are usually considered for risk assessment. It is questionable if this procedure is adequate and it demonstrates the need for a better knowledge concerning relative PA toxicities. With an increase in the extensive production of plants for tea and herbal infusions and the intended reduction in herbicide use, natural toxins such as PAs are likely to become an increasing problem.In the past, several toxicity studies with laboratory animals were conducted for a limited number of PAs. Monitored endpoints were the acute toxic effects, such as lethality or morphological changes in organs. Although hints for a structure-dependent toxicity exist, no conclusions on the relative toxicities of individual PAs can be drawn due to the limited number of tested PAs and due to study designs that limited the comparability of data and the calculation of relative potencies.It is the goal of this project to apply in vitro test systems with different toxicological endpoints that enable the quantitative analysis of toxic effects of PAs. Meanwhile a higher number of PA standards are commercially available which cover a broad range of different structural types. These will theefore be tested in parallel for genotoxicity in bacteria and mammalian cells and for cytotoxicity in liver cells. The data will be used for assessing relative PA toxicities. As PAs are pro-toxins and toxicity is caused after their metabolic activation only, there has to be a strong relationship between metabolism and toxicity. The quantification of known products and identification of unknown metabolites is therefore an important step towards a rational approach explaining differences in toxicity. The correlation of in vitro tests and metabolism data will be used as tool for a better understanding of PA toxicity, a key to risk assessment of relative PA toxicities.
- Technical University of Kaiserslautern, Germany