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Protein and Lipid Binding Parameters in Rainbow Trout (Oncorhynchus mykiss) Blood and Liver Fractions to Extrapolate from an in Vitro metabolic Degradation Assay to in Vivo Bioaccumulation Potential of Hydrophobic Organic Chemicals
Citation:
ESCHER, B., C. COWAN-ELLSBERRY, S. DYER, M. R. EMBRY, S. ERHARDT, M. HALDER, J. KWON, K. JOHANNING, M. T. OOSTERWIJK, S. RUTISHAUSER, H. SEGNER, AND J. W. NICHOLS. Protein and Lipid Binding Parameters in Rainbow Trout (Oncorhynchus mykiss) Blood and Liver Fractions to Extrapolate from an in Vitro metabolic Degradation Assay to in Vivo Bioaccumulation Potential of Hydrophobic Organic Chemicals. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, 24(7):1134-1143, (2011).
Impact/Purpose:
Biotransformation reduces the extent to which environmental contaminants accumulate in fish and other aquatic biota. Unfortunately, the tendency for compounds to be metabolized is not easily predicted from phys ico-chemical properties (e.g., octanol:water partitioning) or an examination of chemical structure. To address this shortcoming, in vitro systems derived from liver tissue have been used to measure metabolism. This information is then extrapolated to the intact animal to predict in vivo metabolism and, by using appropriate computational models, the extent to which chemicals are likely to accumulate in fish. Metabolism is thought to operate against the free chemical fraction in vitro and in vivo. A critical part of this extrapolation approach, therefore, is the need to take into account chemical binding effects. This paper presents in vitro binding data for several well-known environmental contaminants in blood plasma and a widely used (S9 fraction) in vitro metabolizing system. The data are then used to predict steady-state bioconcentration factors (BCFs) for fish. The paper describes a novel system for measuring chemical binding in biological material and provides new data that can be used to develop predictive binding algorithms. As such, this paper substantially advances current efforts to develop in vitro-in vivo metabolism extrapolation procedures for fish.
Description:
Biotransformation reduces the extent to which environmental contaminants accumulate in fish and other aquatic biota. Unfortunately, the tendency for compounds to be metabolized is not easily predicted from physico-chemical properties (e.g., octanol:water partitioning) or an examination of chemical structure. To address this shortcoming, in vitro systems derived from liver tissue have been used to measure metabolism. This information is then extrapolated to the intact animal to predict in vivo metabolism and, by using appropriate computational models, the extent to which chemicals are likely to accumulate in fish. Metabolism is thought to operate against the free chemical fraction in vitro and in vivo. A critical part of this extrapolation approach, therefore, is the need to take into account chemical binding effects. This paper presents in vitro binding data for several well-known environmental contaminants in blood plasma and a widely used (S9 fraction) in vitro metabolizing system. The data are then used to predict steady-state bioconcentration factors (BCFs) for fish. The paper describes a novel system for measuring chemical binding in biological material and provides new data that can be used to develop predictive binding algorithms. As such, this paper substantially advances current efforts to develop in vitro-in vivo metabolism extrapolation procedures for fish.