1. Uptake and elimination kinetics of toxicants in the real world Tjalling Jager & Elke Zimmer Dept. Theoretical Biology TexPoint fonts used in EMF. Read the TexPoint manual before you delete this box.: AAAAA A A A A

2. Toxicokinetics... What is it? processes that link environmental concentrations to concentrations inside an organism Where exactly? in the whole body, or in a specific organ or tissue Why should we care?

3. Range of models From simple...To complex...

4. One-compartment model Assumptions organism is homogeneous, ‘well-mixed’ uptake proportional to external concentration elimination proportional to internal concentration

5. One-compartment model ? But for a real organism … can we assume it is ‘well-mixed’? can we assume constant composition? what about growth? what about reproduction? can DEB help?

6. DEB and diffusion From Fick’s first law: Questions: what is relevant bioconcentration factor P Vd ? what is relevant surface area A ? what is relevant volume V ?

7. Link to DEB Assumptions for composition reserve and buffer have same composition distribution chemical over internal compartments is fast Consequence total bioconc. factor is weighted sum of components buffer structure reserve

8. Link to DEB Assumptions for surface area area for chemical exchange is proportional to structure only Consequence buffer structure reserve water

9. Link to DEB Assumptions for reproduction buffer and egg have same composition chemicals from buffer are transferred to egg Consequence TK depends on buffer buildup and handling buffer structure reserve water eggs

10. Link to DEB Assumptions for buffer chemical follows reserves associated with eggs rest remains in buffer buffer eggs overhead remainder reserve chemical

11. Simulations

15. Assumptions realistic? Difficult to say...  Most test setups avoid growth, reproduction, toxicity and changes in feeding status...  Russell et al 1999: lipid-normalised concentrations in fish and eggs are similar

16. Link to reality? buffer structure reserve eggs water

17. Summarising  TK models range from simple to complex simplest is one-comp. model with constant parameters  DEB offers logical extensions to the real world one-compartment model with time-varying parameters TK becomes closely integrated with the DEB organism 1-2 extra parameters needed …  Model behaviour can become pretty complex growth, reserves, reproduction, buffer handling all affect TK toxicants can indirectly influence their own TK

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