uptake and elimination kinetics of toxicants in the real world

Uptake and elimination kinetics of toxicants in the real world

Tjalling Jager & Elke Zimmer

Dept. Theoretical Biology

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?

Range of models

From simple ... To complex ...

One-compartment model

Assumptions• organism is homogeneous, ‘well-mixed’• uptake proportional to external concentration• elimination proportional to internal concentration

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?

DEB and diffusion

From Fick’s first law:

Questions:• what is relevant bioconcentration factor PVd ?

• what is relevant surface area A ?• what is relevant volume V ?

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

bufferbufferstructurestructure

reservereserve

Link to DEB

Assumptions for surface area• area for chemical exchange is proportional to structure only

Consequence

bufferbufferstructurestructure

reservereserve

water

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

bufferbufferstructurestructure

reservereserve

water eggseggs

Link to DEB

Assumptions for buffer• chemical follows reserves associated with eggs• rest remains in buffer

bufferbuffer eggseggs

overheadoverhead

remainderremainderreservereservechemicalchemical

Simulations

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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

Link to reality?

bufferbufferstructurestructure

reservereserve

eggseggswater

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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Vacancies• PhD position at SCK-CEN in Mol (Belgium): radiation effects

on duckweed (Lemna minor) with DEB

More information: http://www.bio.vu.nl/thb

Also, check out: http://cream-itn.eu/