An isolated perfused fish liver model to study the mechanisms of clearance of organic chemicals

Date: March 23, 2022 4:00 pm (ET)


  • Markus Brinkmann
    University of Saskatchewan

Abstract: The bioconcentration potential of chemicals is an important information criterion in chemical risk assessment. There is growing concern in academia, governments, and industries regarding the suitability and reproducibility of current methods and models to measure and predict bioconcentration potential of readily biotransformed chemicals. Alternative approaches using in vitro biotransformation assays based on hepatocytes or liver sub-cellular fractions in combination with in vitroin vivo extrapolation (IVIVE) models have been developed as potential replacements. However, extrapolation to whole-body bioconcentration factors (BCF) is complicated by a variety of confounding factors. Therefore, there is a need for an ex situ model at an intermediate level of biological organization. A recently developed isolated perfused rainbow trout liver model seeks to reduce uncertainty of extrapolated clearances of chemicals in IVIVE. In this presentation, I will highlight some of the recent progress we have made to further advance this tool. In one study, we have obtained hepatic clearance data for five environmental contaminants of interest within isolated perfused livers and cross-validated with results of in vitromethods, demonstrating an excellent fit between predicted and measured hepatic clearances. In another study, we established methods for running both in vitro and ex situexperiments with low-concentration mixtures of chemicals, here antipsychotic drugs, and establish methods for studying clearance mechanisms other than biotransformation, in particular active transport. These studies significantly advance our ability to assess the biotransformation potential of chemicals in a holistic and functional test, and furthermore underline the predictive power of IVIVE of biotransformation potential of chemicals.

Biography: Dr. Brinkmann (PhD) is an Assistant Professor at the University of Saskatchewan’s School of Environment and Sustainability, the Toxicology Centre, and the Global Institute for Water Security. Markus obtained his PhD from RWTH Aachen University in Germany, and moved to Saskatoon in 2016 to begin a prestigious Banting postdoctoral fellowship with Markus Hecker at the University of Saskatchewan, where he was hired as an Assistant Professor in 2018. An Aquatic Toxicologist by training, his research focusses on contaminants in the water cycle, with a recent emphasis on urban stormwater runoff and municipal wastewater and their impacts on aquatic organisms. Additionally, Markus has made significant contributions in the field of toxicokinetic modelling and in vitro-in vivo extrapolation – he will present some of his most recent advances in this field today.