MA5 Novel Methods for Bioaccumulation Assessment
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() Assessing the bioaccumulation potential of hydrophobic compounds: a comparison of two in vitro digestion models.

Vasiluk, L1, Walji, Z1, Smith, S1, Pinto, L1, Eickhoff, C2, Moore, M1, 1 Simon Fraser University, Burnaby, BC, Canada2 Vizon SciTec Inc., Vancouver, BC, Canada

ABSTRACT- Current methods to determine oral bioavailability are based on tests in animals; however, animal testing is impractical for large-scale screening, e.g. Environment Canada plans to evaluate >21,000 chemicals for their bioaccumulation potential. Therefore, accurate, reproducible and inexpensive in vitro screening models are urgently needed. The overall aim of this project was to develop a screening tool for estimating the oral bioavailability of hydrophobic organic contaminants (HOCs) from a solid matrix (soil, sediment, food). We studied the bioavailability of two HOCs bound to a solid matrix, chrysene (CHR) and benzo[a]pyrene (BaP), in a model digestive system. The intestinal epithelium was modeled using cultured human enterocytes (Caco-2), or ethylene vinyl acetate (EVA). The fugacity capacity (Z) of intestinal fluid for CHR was higher than water (313 vs 235 mol/m3*Pa). The kinetics of CHR partitioning from the aqueous phase to EVA or Caco-2 were similar and best fit a one-compartment model. CHR uptake by EVA and Caco-2 cells showed no significant difference in the rate constants, i.e., both were limited by resistance of the aqueous interphase. Similar kinetics for EVA thin film and Caco-2 cells imply that EVA is a good surrogate for Caco-2 cells which overcomes some of the limitations of tissue culture models. Lipid-normalized fugacity values of Caco-2 cells were 8-fold higher than EVA, indicating that biological lipids have a fugacity capacity ∼25-fold higher than octanol. In transport experiments, Caco-2 cells were incubated with 14C-BaP bound to skim milk powder. Approximately 20% of the radioactivity bound to cells. However, <1% of the radioactivity was transported to the basal medium, indicating that 80% of BaP/BaP metabolites were retained in the lumenal/apical compartment. These results show that the two models provide complementary information that can be used to predict the relative in vivo oral bioavailabilities of HOCs.

Key words: bioavailability, bioaccumulation potential, Caco-2, in vitro

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