Dose Extrapolation Models

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Dose Extrapolation Models

• Fish Physiologically Based Toxicokinetic Models

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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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Jims Question

• Can fish PBTK models be used to accurately
  predict uptake, disposition, and elimination of
  organic chemicals, across routes of uptake and
  across species?

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Concentration of three chlorinated ethanes in
arterial blood of channel catfish
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Concentration of three chlorinated ethanes in
arterial blood of rainbow trout
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Concentration of three chlorinated ethanes in
liver of lake trout
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Bioconcentration model for small fish
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Rate constants (L/h) used to predict branchial
and cutaneous uptake of TCB
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Observed and predicted clearance of TCB by
Fathead Minnow
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PBTK model for small fish
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Concentration of TCB in contents of stomach ( )
upper intestine ( ) and lower intestine ( )
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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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