Category Research project
  • Toxikologie

Studies on the transfer of pyrrolizidine alkaloids to farm animals

Project status
Completed
Project start
2019
Project end
Mar 2024
Acronym
PA-SAFE-FEED
Department
Sicherheit in der Nahrungskette

Description and Objective

Knowledge of the fate of liver-toxic pyrrolizidine alkaloids (PA) and their N-oxides (PANO) in livestock and the possible transfer to food of animal origin is currently incomplete for a reliable assessment of the risks of contamination of feed and for deriving risk management measures. Within the framework of this collaborative project, feeding studies in sheep, goats and cattle, among others, are carried out. The samples obtained from these trials such as animal tissues and organs, milk and other body fluids will be analysed for PA/PANO. BfRshort forGerman Federal Institute for Risk Assessment is concerned with the analytical detection of PA/PANO and in particular their metabolites in samples from in vivo feeding studies. In addition, BfRshort forGerman Federal Institute for Risk Assessment is focusing on accompanying in vitro studies on (a) ruminal metabolism, (b) tissue mobility during passage through the intestinal wall, and (c) hepatic metabolism in microsomes and cytochrome P450 preparations from liver cells. The analysis of the samples is carried out at BfRshort forGerman Federal Institute for Risk Assessment using modern methods (high-resolution mass spectrometry in combination with software-supported evaluation of the analysis data obtained), which enable sensitive and highly specific identification of metabolites with structural relationship to PA/PANO in the various samples of the in vivo and in vitro studies on the basis of extensive expertise. The project goal related to the BfRshort forGerman Federal Institute for Risk Assessment focus is to clarify the fate of the fed PA/PANO in the animal. In doing so, metabolic changes of PA/PANO have to be traced and balances have to be completed. Based on the data obtained, the assessment of risks for the health of farm animals and for the consumer, as a consumer of food of animal origin, will be improved.

Result

As part of the PA-SAFE-FEED project, a 28-day feeding study was conducted with lactating cows, sheep, and goats, in which three dose levels each of an extract of common ragwort (Jacobaea vulgaris Gaertn.) were administered orally, including at least one control group. The animals were evaluated for performance and health parameters. Liver-associated parameters, including blood liver enzymes, were identified as toxicological endpoints in the three species. Additionally, the concentrations of pyrrolizidine alkaloids (PA) and their N-oxides (PANO) were quantified in milk and meat as products intended for human consumption. Based on these data, transfer parameters were established for both total-PA and individual Senecio-PAs. It was found that there is a low and selective transfer into animal products, with the content in milk and meat mainly consisting of jacoline, jaconine, jacobine and senkirkine.
In addition to the feeding study, in vitro studies on the ruminal and hepatic metabolism of Senecio-PAs were carried out. These studies, particularly in conjunction with results of a kinetic study performed with pure substances (single-dose administration of retrorsine or retrorsine-N-oxide, resp.), provide a better understanding of the fate of PAs and their metabolites.
Type of project

Third-party funded project

Research focus

Futtermittelsicherheit / Nachweis von Kontaminanten und zur Bewertung chemischer Risiken

Organisational units and partners

Lead specialist group: Toxine (52)
Contact persons: Dr. Matthias Gehling
External partner: Max Rubner-Institut, Bundesforschungsinstitut für Ernährung und Lebensmittel, Ludwig-Maximilians-Universität München

Funding body and grant number

Bundesministerium für Ernährung und Landwirtschaft
2818NA006