MP11 Advances in Bioaccumulation Assessment
Monday, 14 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(ERH-1117-738835) Interspecies Comparisons of Metabolism using Liver S9 Fractions.

Erhardt, S¹, Weisbrod, A², Roe, A³, ¹ The Dow Chemical Company, Toxicology and Environmental Testing and Consulting, Midland, MI, USA² Procter & Gamble, Central Product Safety - Environmental, Cincinnati, OH, USA³ Procter & Gamble Pharmaceuticals, Drug Safety Assessment, Cincinnati, OH, USA

ABSTRACT- An international industry, government and academic consortium has undertaken to develop and validate a tiered series of methods that can be used to generate absorption, distribution, metabolism, and excretion (ADME) data for use in predicting the bioaccumulation (B) potential of chemicals in aquatic organisms. Methodologies to examine the metabolism of xenobiotics include in vitro approaches utilizing subcelluar fractions of fish liver. Characterization of the metabolism of standard substrates and commercial substances by fish liver S9 preparations is underway as a means to generate metabolism data for application to B models and assessments. Our fish studies are based on standardized in vitro methods used to assess metabolic activity in mammalian systems such as rat, dog and human. In the process of characterizing enzyme activity levels in fish S9, we are attempting to standardize the incubation conditions e.g., incubation temperature, and protein and substrate concentration. An understanding of the types of enzymatic activity in trout and carp, relative to better characterized mammalian systems, is expected to allow for interspecies extrapolation and ultimately the use of existing data for modeling aquatic bioaccumulation. Interspecies comparisons will be presented with regards to types of enzymatic systems, levels of activity, and transformation processes detected in S9 fractions. Suggestions on how to proceed with interspecies extrapolation will also be presented.

Key words: in vitro metabolism, trout S9, interspecies extrapolation