ALTERTOX aims to clarify following research questions:
- What is the in vitro cytotoxicity of alternariol, alternariol-monomethylether, tenuazonic acid and relevant mixtures thereof towards intestinal epithelial cells and hepatocytes of human and porcine origin? This will enable the calculation of the mycotoxin concentration at which 50% of the cells show loss in viability (EC50 endpoint), and to determine the “lowest-observed-adverse-effect level” (LOAEL) and “no-observed-adverse-effect level” (NOAEL). These toxicological endpoints will serve as “Point of Departure” (POD) for further risk assessment.
- Is there an in vitro genotoxic effect of alternariol, alternariol-monomethylether, tenuazonic acid and relevant mixtures thereof in intestinal epithelial cells and hepatocytes of human and porcine origin? This will also allow the calculation of EC50, LOAEL and NOAEL toxicological endpoints, and of PODs.
- What are the in vivo toxicokinetic characteristics and toxicokinetic parameters, including absorption and absolute oral bioavailability, distribution, phase I and II metabolism and excretion (ADME properties) of alternariol, alternariol-monomethylether and tenuazonic acid in pigs, as most relevant and superior animal model for humans?
These research questions will be answered using both in vitro porcine and human cell culture models representative for the gastrointestinal tract and liver, and using an in vivo porcine animal model to study the oral bioavailability and toxicokinetics, as most relevant and superior surrogate animal model for humans.