Human Bioaccumulation Potential simulated in R and implemented in the KNIME Interface

The assessment of human bioaccumulation potential is an important element in the risk assessment of chemicals. Tonnelier et al. (Arch Toxicol (2012) 86: 393–403) developed a generic physiologically based toxicokinetic (PBTK) model which, based on in vitro human liver metabolism data, minimal renal excretion and a constant exposure scenario, was able to predict the bioaccumulation potential of a chemical, expressed as the human bio concentration factor (hBCF). This model was designed to incorporate not only the chemical properties of the compounds, but also the processes that tend to decrease the concentration of the compound, such as metabolism. Following this work we have implemented the generic PBTK model, now written in R, in the open source KNIME interface. The KNIME workflow consists of several nodes: (1) a database connector (with biophysical properties of specific compound) with a query filter node to select the values for the simulated chemical; (2) an XLS reader node that provides the model input parameters (e.g. flow rates, organ volume); (3) an R node where the PBTK model is described mathematically; and (4) an R view node for output. The outputs are: a figure expressed as concentration versus time and the hBCF. The hBCF values can be used to rank chemicals for their potency which can assist in risk making decisions. Examples applied to selected chemicals will be shown. This open source approach will help in performing in vitro–in vivo extrapolation (IVIVE) in the risk assessment process without the use of animal experiments.

PAINI Alicia;  SALA BENITO Jose';  GAJEWSKA Monika;  WORTH Andrew;  ZALDIVAR COMENGES José M; 

2013-12-11

Seurat - 1, COACH consortium

JRC80962

978-2-9539634-2-7,