Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 64841
Title A physiologically based pharmacokinetic (PB-PK) model for ethylene dibromide; relevance of extrahepatic metabolism
Author(s) Hissink, A.M.; Wormhoudt, L.W.; Sherratt, P.J.; Hayes, J.D.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, P.J. van
Source Food and Chemical Toxicology 38 (2000). - ISSN 0278-6915 - p. 707 - 716.
Department(s) Toxicology
Publication type Refereed Article in a scientific journal
Publication year 2000
Abstract A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new data were used for the human class ΘGST T1-1. Validation experiments are described in order to test the predictive value of kinetics to describe "whole-body" metabolism. For the validation experiments, groups of cannulated rats were dosed orally or intravenously with different doses of EDB. Obtained blood concentration–time curves of EDB for all dosing groups were compared to model predictions. It appeared that metabolism, which previously was assumed to be restricted to the liver, was underestimated. Therefore, we extended the PB-PK model to include all the extrahepatic organs, in which the enzymes involved in EDB metabolism have been detected and quantified. With this extended model, the blood concentrations were much more accurately described compared to the predictions of the "liver-model". Therefore, extrahepatic metabolism was also included in the human model. The present study illustrates the potential application of in vitro metabolic parameters in risk assessment, as well as the use of PB-PK modelling as a tool to understand and predict in vivo data.
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