uptake and elimination kinetics of toxicants in the real world
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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.: A A A A A A A A A. Toxicokinetics. What is it? - PowerPoint PPT PresentationTRANSCRIPT
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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concentration structure
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concentration reserves
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concentration total
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concentration structure
time0 20 40 60
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concentration reserves
time0 20 40 60
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concentration total
time
Simulations
0 20 40 600
0.05
0.1
0.15
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structural length
time0 20 40 60
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physical length
time0 20 40 60
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cumul. reproduction
time
0 20 40 600
5
10
15
concentration structure
time0 20 40 60
0
5
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15
concentration reserves
time0 20 40 60
0
5
10
15
concentration total
time
Simulations
0 20 40 600
0.05
0.1
0.15
0.2
structural length
time0 20 40 60
0
0.05
0.1
0.15
0.2
physical length
time0 20 40 60
0
1000
2000
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4000
cumul. reproduction
time
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5
10
15
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30
concentration structure
time0 20 40 60
0
5
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30
concentration reserves
time0 20 40 60
0
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concentration total
time
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/