Transcript General Unified Threshold model for Survival

Time is of the essence!
Tjalling Jager
Dept. Theoretical Biology
Challenges of ecotox
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Some 100,000 man-made chemicals
For animals alone, >1 million species described
Complex dynamic exposure situations
Species interact dynamically in ecosystems
We cannot (and should not) test all permutations!
Extrapolation
“Protection goal”
Laboratory tests
time is of the essence!
Fate modelling
environmental
characteristics and
emission pattern
mechanistic
fate model
physico-chemical
properties under
laboratory conditions
concentrations
over time and
space
Fate modelling
pesticide fate modelling
oil-spill modelling
Classic ecotox
Description for:
• one endpoint
• one timepoint
• constant exposure
• one set of conditions
NOEC
EC50
effects data over
time for one (or few)
set(s) of conditions
summary statistics
prediction effects
in dynamic
environment
Learn from fate modelling
proper
measures of
toxicity
that do not depend on
time or conditions
mechanistic
model for
species A
effects data over
time for one (or few)
set(s) of conditions
prediction effects
in dynamic
environment
Data analysis
life-history
information of
the species
test conditions
model
parameters for
toxicant
mechanistic
model for
species A
effects data over
time for one (or few)
set(s) of conditions
model
parameters for
species
model parameters that
do not depend on time
or conditions
Educated predictions
dynamic environment:
exposure and
conditions
model
parameters for
toxicant
prediction lifehistory traits
over time
only for one species ...
mechanistic
model for
species A
model
parameters for
species
model parameters that
do not depend on time
or conditions
Community effects
model
parameters
for toxicant
model
parameters
for species A
mechanistic
model for
species A
dynamic environment
model
parameters
for toxicant
model
parameters
for species A
mechanistic
model for
species B
mechanistic
model for
a community
simulate community
effects and recovery
over time
What individual model?
model
parameters
for toxicant
model
parameters
for species A
mechanistic
model for
species A
dynamic environment
TKTD modelling
toxicodynamics
external
concentration
(in time)
toxico-kinetic
model
internal
concentration
in time
process model
for the organism
toxicokinetics
effects on
endpoints
in time
TKTD modelling
external
concentration
(in time)
toxico-kinetic
model
internal
concentration
in time
toxicokinetics
TKTD modelling
toxicodynamics
internal
concentration
in time
process model
for the organism
effects on
endpoints
in time
Organisms are complex …
process model
for the organism
Learn from fate modellers
Make an idealisation of the system
 how much biological detail do we minimally need …
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to explain how an organism grows, develops and reproduces
to explain effects of stressors on life history
to predict effects for untested situations
without being species- or stressor-specific
internal
concentration
in time
process model
for the organism
effects on
endpoints
in time
Dynamic Energy Budget
Organisms obey mass and energy conservation
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find the simplest set of rules ...
over the entire life cycle ...
for all organisms (related species follow related rules)
most appropriate DEB model depends on species and question
resources
offspring
waste products
growth
maturation
maintenance
Kooijman (2010)
The “DEBtox” concept
external
concentration
(in time)
toxicokinetics
internal
concentration
in time
DEB
parameters
in time
repro
growth
DEB
model
survival
feeding
hatching
…
The “DEBtox” concept
external
concentration
(in time)
toxicokinetics
internal
concentration
in time
DEB
parameters
in time
repro
growth
DEB
model
survival
feeding
hatching
DEB parameter cannot be measured …
Internal concentration are often not measured …
…
“Standard” tests ...
mechanistic
model for
species A
model
parameters for
toxicant
model
parameters for
species
constant exposure,
ad libitum food
Many DEBtox examples, e.g.:
http://www.bio.vu.nl/thb/users/tjalling
Dynamic exposure
mechanistic
model for
species A
model
parameters for
toxicant
model
parameters for
species
dynamic exposure pattern,
different food levels ...
Daphnia magna and fenvalerate
– modified 21-day reproduction test
– pulse exposure for 24 hours
– two (more or less) constant food levels
Pieters et al (2006)
Pulse exposure
Body length
Cumulative offspring
Fraction surviving
70
1
High food
4
60
40
2
0.6
30
0.4
20
1
0.2
‘assimilation’
mode
10 of action:
0
0
Insights
70
• parameters
independent of food1
60
• chemical
effects fully reversible0.8
50
• reproduction
rate slows down …
40
0
4
Low food
0.8
50
3
3
0.6
2
30
0.4
20
1
0.2
10
0
0
5
10
15
20
0
0
5
10
15
20
0
0
5
10
15
20
Work needed
For the individual level
– select relevant species and appropriate DEB models
– adapt/develop model code, allow time-variable inputs
– collect and analyse relevant existing test data
Evaluate
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are DEB models useful?
what are limitations?
what are major gaps in knowledge?
what test protocol is most useful?
mechanistic
model for
species A
mechanistic
model for
species B
Community level
What makes community different?
– dynamic interactions between species
– less or more sensitive to toxicants?
mechanistic
model for
species A
mechanistic
model for
species B
mechanistic
model for
a community
Community level
Food web models can become rather complex …
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results depend heavily on modelling choices
difficult to parameterise
focus on furry animals …
little general insight gained
not useful for generic RA
Canonical community
Start simple:
– each species a simple DEB model
– closed system (open for energy)
– include nutrient recycling
Canonical community
Start simple:
– each species a simple DEB model
– closed system (open for energy)
– include nutrient recycling
nutrients
producer
light
consumer
decomposer
detritus
predator
Using the DEB community
previous project at VU-ThB (EU-MODELKEY)
collaboration with SCK-CEN, Belgium (EU-STAR)
nutrients
producer
light
consumer
decomposer
detritus
predator
Using the DEB community
previous collaborations, e.g., Univ. Antwerp (EU-NoMiracle, EU-OSIRIS)
collaboration with UFZ, Leipzig (EU-CREAM)
nutrients
producer
light
consumer
decomposer
detritus
predator
Using the DEB community
collaboration with Eawag, Switzerland (EU-CREAM)
collaboration with IRSN, France
nutrients
producer
light
consumer
decomposer
detritus
predator
Using the DEB community
previous projects at VU-ThB
nutrients
producer
light
consumer
decomposer
detritus
predator
Work needed
For the community level
– specify interactions between the species
– code a community with DEB populations
– simulations for various scenarios
Evaluate
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what’s different at the community level?
more or less effect?
correspondence to e.g., mesocosm?
identify major gaps in knowledge
mechanistic
model for
a community
Wrapping up
Time is of the essence!
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an organism is a dynamic system …
that interacts dynamically with others …
in a dynamic environment …
with dynamic exposure to chemicals
NOEC, EC50 etc. are useless …
time is of the essence!
Wrapping up
Mechanistic models essential for the individual
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to extract time-independent parameters from data
to extrapolate to untested dynamic conditions
to increase efficiency of risk assessment
learn from fate and toxicokinetics modellers …
Integrate models into a simple community
– study how interactions affect toxicant responses
– study recovery of the community
Wrapping up
Advantages of using DEB as basis
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well-tested theory for individuals
mechanistic, dynamic, yet (relatively) simple
deals with the entire life cycle
not species- or chemical-specific
small but well-connected international DEB community
resources
offspring
waste products
growth
maturation
maintenance
Wrapping up
This project tries to deliver “proof of concept”
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can DEB serve as a general platform?
can simple mechanistic community models help RA?
how can we modify test protocols?
where are the major stumbling blocks?
More information
on DEB:
http://www.bio.vu.nl/thb
on my work: http://www.bio.vu.nl/thb/users/tjalling
time is of the essence!
body length
cumulative offspring
Ex.1: maintenance costs
time
Jager et al. (2004)
TPT
time
body length
cumulative offspring
Ex.2: growth costs
time
Alda Álvarez et al. (2006)
Pentachlorobenzene
time
Ex.3: egg costs
body length
cumulative offspring
Chlorpyrifos
time
Jager et al. (2007)
time