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Gastrointestinal absorption processes of substances: Do they have an impact on bioaccumulation?

: Zwintscher, Ariane; Hahn, Stefan; Kühne, R.; Schuurmann, G.; Drost, W.; Ackermann, J.; Joehncke, U.; Schlechtriem, C.; Nendza, M.

Society for Environmental Toxicology and Chemistry -SETAC-:
SETAC Europe 24th Annual Meeting 2014. Abstract book : Science across bridges, borders and boundaries, Basel, Switzerland, 11-15 May 2014
Brussels: SETAC Europe, 2014
ISSN: 2309-8031
S.314, WE194
Society of Environmental Toxicology and Chemistry (SETAC Annual Meeting) <24, 2014, Basel>
Fraunhofer ITEM ()

According to experiences in bioaccumulation studies in fish it is known that not for all classes of substances the bioaccumulation potential can be explained by their lipophilicity / hydrophobicity. The aim is to elaborate a strategy for identifying substances with increased bioaccumulation by absorption processes in the gastrointestinal tract (GIT). Therefore, accumulation processes in the GIT have been evaluated to get a first impression of the gastrointestinal absorption behavior of molecules. A compilation of different transport mechanisms, transporter types and the occurrences in different species will form a basis for discussion of the described effects. Especially for pharmaceuticals the caco-2 assay (human carcinogenic intestinal epithelium) is often used to investigate uptake processes in the GIT. Since this cell line represent both active and passive transport processes, the possibility to use the caco-2 cell line for prediction of increased bioaccumulation is examined. Therefore several measured and estimated caco-2 data-sets were plotted against logD (log Kow). In addition, the correlation to experimental bioaccumulation values was verified. In a first approach BCF values have been used as not enough BMF values are available. In the GIT different absorption mechanisms are relevant: passive permeability and active transport (primary and secondary). While passive uptake can often be predicted from molecule specific properties (log Kow, MW, charge) the secondary active transport enables also e.g. highly water-soluble substances to resolve embranes. Therefore, secondary active transport processes such as PEPT1, which is distributed throughout different animal species and humans, might lead to an underestimation of molecules ability to account for higher BCF values than predicted. First results indicate that data from caco-2 cell assays can indeed give some information for substances with probably higher bioaccumulation potential than predicted by the conventional approach based on lipophilicity. Thus, caco-2 data could form a basis to develop an estimation tool for identifying such substances. However, at first, the data base should be extended by experimental caco-2 values for selected industry chemicals, pesticides or biocides. As a perspective the estimation tool could be integrated in decision trees for bioaccumulation testing in a regulatory context (e.g. REACh).