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Dose Extrapolation Models

Dose Extrapolation Models. Fish Physiologically Based Toxicokinetic Models. Acknowledgements. James McKim Russell Erickson John Nichols Melvin Andersen Michael Gargas Harvey Clewell III Alex Hoffman Doug Kuehl Correne Jenson Sharon Bertelsen Partrick Fitzsimmons Frank Whiteman.

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Dose Extrapolation Models

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  1. Dose Extrapolation Models Fish Physiologically Based Toxicokinetic Models

  2. Acknowledgements • James McKim • Russell Erickson • John Nichols • Melvin Andersen • Michael Gargas • Harvey Clewell III • Alex Hoffman • Doug Kuehl • Correne Jenson • Sharon Bertelsen • Partrick Fitzsimmons • Frank Whiteman

  3. Jim’s Question: “Can fish PBTK models be used to accurately predict uptake, disposition, and elimination of organic chemicals, across routes of uptake and across species? ”

  4. Concentration of three chlorinated ethanes in arterial blood of channel catfish

  5. Concentration of three chlorinated ethanes in arterial blood of rainbow trout

  6. Concentration of three chlorinated ethanes in liver of lake trout

  7. Bioconcentration model for small fish

  8. Rate constants (L/h) used to predict branchial and cutaneous uptake of TCB

  9. Observed and predicted clearance of TCB by Fathead Minnow

  10. PBTK model for small fish

  11. Concentration of TCB in contents of stomach ( ) upper intestine ( ) and lower intestine ( )

  12. Conclusions: • PBTK models can be used to accurately predict uptake, elimination, and disposition of organic chemicals in fish. • PBTK models can be used to accurately predict dose in fish via branchial, cutaneous and gut uptake. • PBTK models can be used to accurately extrapolate dose across fish species.

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