MA5 Novel Methods for Bioaccumulation Assessment
203 Oregon Ballroom
8:00 AM - 12:00 PM, Monday
() Clearance of Xenobiotics by Isolated Trout Hepatocytes: Accounting for Metabolism in Prediction of Bioaccumulation Potential.
Kemper, R1, Nabb, D1, Samel, A1, 1 DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE, USA
ABSTRACT- For the past decade, there has been an increasing demand to better understand the potential for chemicals to persist in the environment and to accumulate through the food chain. Only a handful of chemicals currently in commerce have been tested for bioconcentration or bioaccumulation potential, and the large number of compounds to be tested coupled with the resource intensive nature of standard testing methods for this endpoint precludes comprehensive testing. For these reasons, regulatory agencies and chemical producers rely on computational models to predict bioaccumulation potential of xenobiotics based on structure, physico-chemical properties and other descriptors. One shortcoming of many bioaccumulation models is that metabolism in the target species (usually fish) is neglected. In this presentation, an approach for coupling in vitro metabolism data with computational modeling of bioaccumulation is proposed, using trout as a model species. The disappearance kinetics of test compounds in freshly isolated trout hepatocytes are measured and used to calculate an in vitro intrinsic clearance. This value is then scaled up to a whole animal hepatic clearance value based on hepatocellularity, relative organ weight and hepatic blood flow. Whole animal clearance is converted to a metabolic elimination rate constant that can be used as an input to correct bioaccumulation model predictions. The value of such an approach can be expanded through the use of data mining/data visualization tools to logically cluster groups of structurally similar compounds and select representative compounds for testing, which cover the chemical space of the overall group. The proposed approach provides an alternative to cost-prohibitive standard test methods and may improve the predictive power of current computational models for bioaccumulation.
Key words: bioaccumulation potential, xenobiotics