PH11 Bioaccumulation and Biotransformation of POPs
Exhibit Hall
8:00 AM - Thursday, 13 November 2003
(PH100) Development and evaluation of a physiologically based toxicokinetic (PBTK) model for fluoranthene in rainbow trout.
Smith, C 1, Wright, S1, Oris, J1, 1 Miami University, Oxford, OH, USA
ABSTRACT- Polycyclic aromatic hydrocarbons (PAH) are ubiquitous in aquatic environments and several studies have shown that PAH are both chronic and acutely toxic to aquatic organisms. Therefore, risk managers seek to understand the toxicokinetic relationships linking PAH contamination, target tissue dose and toxic response. Physiologically based toxicokinetic models (PBTKs) have been suggested to be the most realistic toxicokinetic tool to describe the movement of a toxicant throughout biologically meaningful compartments, such as kinetically related tissues and organs. In this study, a PBTK model was developed to predict the uptake of waterborne fluoranthene, a common PAH, in male and female rainbow trout (Oncorhynchuss mykiss). The model predicts the time course of fluoranthene in eight compartments: the gills, liver, kidney, fat, poorly perfused tissues, richly perfused tissues, gonads, and brain. Special attention was given to the brain and gonad compartments since it has been hypothesized that these tissues are the targets of PAH-induced reproductive toxicity. To predict fluoranthene kinetics in an individual rainbow trout, the model was solved using the mean value of input parameters estimated experimentally or obtained from the literature. To predict fluoranthene kinetics in a population of rainbow trout, Monte Carlo simulation was employed wherein a range of values for each input parameter were repeatedly sampled to generate a range of model outputs. The model was evaluated by exposing rainbow trout to fluoranthene and comparing measured versus predicted kinetics. Preliminary results indicate a good fit between model predictions and measured uptake. The results of this study may help elucidate processes governing PAH-induced reproductive toxicity. Future applications of this model in real-world scenarios will provide further evidence for the use of PBTK models as risk assessment tools.
Key words: Toxicokinetic, Physiologically-based, Fluoranthene, Rainbow trout