MIP1PM Advances in Bioaccumulation Assessment
Monday, 14 November 2005: 1:50 PM - 5:30 PM in 349-350

(DOW-1117-807128) Use of In-Vitro Absorption Models in the Assessment of Bioaccumulation.

Dowty, M¹, Weisbrod, A², Obringer, C¹, ¹ Procter & Gamble Pharmaceuticals, Mason, OH, USA² The Procter & Gamble Company, Cincinnati, OH, USA

ABSTRACT- Recent environmental legislation is forcing regulators and industry to prioritize chemicals for risk management and food chain exposures. Programs for persistent, bioaccumulative, and toxic (PBT) substances are active in North America, Europe, and Asia. Bioaccumulation integrates several internal biological processes: absorption, distribution, metabolism, and excretion (ADME). Incorporation of these aspects should result in improved assessments for bioaccumulation. With respect to absorption, the primary drivers of permeability are hydrophobicity, molecular size, polarity, and charge state. Within the pharmaceutical industry, the in vitro Caco-2 enterocyte cell model has been an important tool to assess the absorption and distribution potential of drugs in various mammals, including humans. The fish intestine and gill have similar permeability properties to mammalian intestine and blood-brain barrier respectively, which should allow for the application of standard pharmaceutical absorption tools to the understanding of absorption potential of compounds in fish. Studies of surfactants and select reference compounds were carried out in the Caco-2 assay; these in vitro data are compared to published in vivo bioaccumulation data for these compounds. The results suggest that permeability can be an important factor affecting bioaccumulation, and that Caco2 data are helpful for the elucidation of chemical bioavailability in vivo in fish.

Key words: absorption, Caco-2, bioaccumulation