Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic modelReport as inadecuate

Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 BIPOP - Modelling, Simulation, Control and Optimization of Non-Smooth Dynamical Systems Inria Grenoble - Rhône-Alpes, LJK - Laboratoire Jean Kuntzmann, INPG - Institut National Polytechnique de Grenoble 2 IHCP - Institute for Health and Consumer Protection

Abstract : Human bioaccumulative potential is an important element in the risk assessment of chemicals. Due to the high number of synthetic chemicals, there exists the need to develop prioritisation strategies. The purpose of this study was to develop a predictive tool for human bioaccumulation risk assessment that incorporates not only the chemical properties of the compounds, but also the processes that tend to decrease the concentration of the compound such as metabolisation. We used a generic physiologically-based toxicokinetic PBTK model that based on in vitro human liver metabolism data, minimal renal excretion and a constant exposure was able to assess the bioaccumulative potential of a chemical. The approach has been analysed using literature data on well-known bioaccumulative compounds and liver metabolism data from the ECVAM database and a subset of the ToxCast phase I chemical library -in total 94 compounds covering pharmaceuticals, plant protection products and industrial chemicals-. Our results provide further evidence that partitioning properties do not allow for a reliable screening criteria for human chemical hazard. Our model, based on a 100% intestinal absorption assumption, suggests that metabolic clearance, plasma protein-binding properties and renal excretion are the main factors in determining if bioaccumulation will occur and its amount. It is essential that in vitro metabolic clearance tests with metabolic competent cell lines as well as plasma protein binding assays be performed for suspected bioaccumulative compounds.

Keywords : Bioaccumulation assessment Screening PBTK modelling In vitro-in vivo extrapolation

Author: Arnaud Tonnelier - Sandra Coecke - José-Manuel Zaldìvar -



Related documents