Bio: Dr. Doris Marko (ERT) is Professor of Food Chemistry at the University of Vienna (Austria) and head of the Department of Food Chemistry and Toxicology. She studied Food Chemistry at the University of Kaiserslautern, Germany. She is a member of several national and international committees in the field of food safety. In her research strategy, she synergistically combines state-of-the-art analytics with toxicological/mechanistical approaches, to address actual questions of consumer safety. Actual fields of research include hazard characterization of emerging contaminants, the complex interaction of contaminants with potentially co-occurring bioactive food constituents or pharmaceutical drugs as well as novel strategies for risk assessment of chemical mixtures.

Abstract: Emerging mycotoxins produced by Alternaria molds frequently occur as food contaminants but are not yet regulated due the incomplete characterization of their toxicity, notably including human toxicokinetics. Physiologically based toxicokinetic (PBTK) modeling is a promising method to predict ADME with minimal additional experimentation. To facilitate the development of respective models for the signature Alternaria toxins alternariol (AOH) and its monomethyl ether (AME), we used LC-MS/MS to quantify their hepatic biotransformation kinetics in subcellular fractions. Phase I metabolism was assessed in rats, porcine and human liver microsomes while glucuronidation was characterized in rat and human liver S9 fractions. Therewith, we unveiled interspecies differences in the pattern and rate of the phase I metabolism but also observed that glucuronidation is the rate-dominant pathway of detoxification for both, AOH and AME. Calculated constants for intrinsic clearance were then used to parameterize a previously developed PBTK model for the dibenzo-α-pyrone chemical class, whose performance was evaluated against available animal toxicokinetic data for AOH. Subsequent cross-species extrapolation yielded a first PBTK model to predict concentrations in human organs of toxicological concern after dietary exposure. These will be used for next generation chemical risk assessment via quantitative in vitro to in vivo extrapolation of toxicity data.