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Chemical Biotransformation in Fish: Implications for Predictive Model Development

Project Summary

Fish metabolically transform many of the chemicals to which they are exposed.  These transformations generally facilitate the removal of a compound from the fish’s body and often, although not always, result in reduced toxicity.  It is important, therefore, to predict the extent to which fish will metabolize compounds of interest and to incorporate these predictions into mathematical models of uptake and accumulation.  The goal of this research effort is to develop in vitro (“test tube”) measures of chemical metabolism that can be extrapolated to the in vivo (“whole animal”) situation.  Once validated, these in vitro assays will provide estimates of metabolism that can be used to predict chemical uptake and accumulation without the prior need to expose live animals.

Key products

The key products of this effort will be a series of peer-reviewed journal publications.  Individual publications will describe: 1) the general method used to perform in vitro-in vivo metabolism extrapolations with fish, 2) existing in vitro data for fish that can be used to perform these extrapolations, and 3) potential impacts of metabolism on chemical accumulation as a function of a compound’s relative hydrophobicity.

Bonnell, M., C. Cowan-Ellsberry, J. Domoradzki, M. Embry, S. Erhardt, M. Halder, J. Nichols, and H. Segner. Moving bioaccumulation assessments to the next level: Progress made and challenges ahead. SETAC, Boston, MA, November 13-17, 2011.

Connors, K., B. Du, P. Fitzsimmons, C. Chambliss, J. Nichols, and B. Brooks. Comparative pharmaceutical metabolism with rainbow trout (Oncorhynchus mykiss) S9. SETAC, Boston, MA, November 13-17, 2011.

Fay, K.A., P.N. Fitzsimmons, A.D. Hoffman, and J.W. Nichols. Use of isolated trout hepatocytes to predict measured hepatic clearance and whole-animal bioconcentration factors for six polyaromatic hydrocarbons. SETAC, Boston, MA, November 13-17, 2011.

Nichols, J., A.D. Hoffman, P.N. Fitzsimmons, K. Fay, and T. Ter Laak. Hepatic clearance of six polyaromatic hydrocarbons by isolated perfused trout livers: Prediction from liver S9 fractions and isolated hepatocyte. PRIMO (Pollutant Responses in Marine Organisms) 16, Long Beach, CA, May 15-18, 2011.

Escher, B.I., C.E. Cowan-Ellsberry, S. Dyer, M.R. Embry, S. Erhardt, M. Halder, J.-H. Kwon, K. Johanning, M.T. Oosterwijk, S. Rutishauser, H. Segner, and J. Nichols. 2011. 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 24:1134-1143.

Cowan-Ellsberry, C., M. Embry, M. Bernhard, S. Dyer, B. Escher, K. Johanning, J. Nichols, and D. Huggett. Extrapolation of BCF from the in vitro rainbow trout (Oncorhynchus mykiss) liver S9 metabolic assay results. SETAC, Portland, OR, November 7-11, 2010.

Embry, M., A. Adekola, M. Bernhard, C. Cowan-Elsberry, S. Dyer, C. Eickhoff, S. Erhardt, B. Escher, M. Halder, G. Hancock, K. Johanning, J. Nichols, and A. Sharpe. Validation of the in vitro rainbow trout (Oncorhynchus mykiss) liver S9 metabolic assay to assess bioaccumulation potential of chemicals. SETAC, Portland, OR, November 7-11, 2010.

Fitzsimmons, P.N., A.D. Hoffman, and J.W. Nichols. Effect of gender on intrinsic clearance of six polyaromatic hydrocarbons by liver S9 fractions from sexually immature rainbow trout. SETAC, Portland, OR, November 7-11, 2010.

Nichols, J., A.D. Hoffman, T. Ter Laak, and P.N. Fitzsimmons. Hepatic clearance of six polyaromatic hydrocarbons by isolated perfused trout livers: Evaluation of protein binding effects. SETAC, Portland, OR, November 7-11, 2010.

Project personnel


Name E-mail Phone
John Nichols nichols.john@epa.gov 218-529-5160
Patrick Fitzsimmons fitzsimmons.patrick@epa.gov 218-529-5184
Alex Hoffman hoffman.alex@epa.gov 218-529-5135

Research project update date

January 23, 2012

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