Time is of the essence!

Time is of the essence! Tjalling Jager Dept. Theoretical Biology

Challenges of ecotox • 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 concentrations over time and space physico-chemical properties under laboratory conditions

pesticide fate modelling oil-spill modelling Fate modelling

Classic ecotox • Description for: • one endpoint • one timepoint • constant exposure • one set of conditions ?? NOEC prediction effects in dynamic environment EC50 effects data over time for one (or few) set(s) of conditions summary statistics

Learn from fate modelling proper measures of toxicity that do not depend on time or conditions mechanistic model for species A prediction effects in dynamic environment effects data over time for one (or few) set(s) of conditions

Data analysis life-history information of the species test conditions model parameters for toxicant mechanistic model for species A model parameters for species model parameters that do not depend on time or conditions effects data over time for one (or few) set(s) of conditions

Educated predictions dynamic environment: exposure and conditions model parameters for toxicant mechanistic model for species A model parameters for species prediction life-history traits over time model parameters that do not depend on time or conditions only for one species ...

Community effects model parameters for toxicant mechanistic model for species A model parameters for species A mechanistic model for a community dynamic environment model parameters for toxicant simulate community effects and recovery over time mechanistic model for species B model parameters for species A

What individual model? model parameters for toxicant mechanistic model for species A model parameters for species A dynamic environment

toxicodynamics internal concentration in time external concentration (in time) effects on endpoints in time toxicokinetics TKTD modelling toxico-kinetic model process model for the organism

internal concentration in time external concentration (in time) toxicokinetics TKTD modelling toxico-kinetic model

toxicodynamics internal concentration in time effects on endpoints in time TKTD modelling process model for the organism

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 … • 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

Kooijman (2010) Dynamic Energy Budget Organisms obey mass and energy conservation • 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

internal concentration in time repro DEB parameters in time growth external concentration (in time) survival feeding hatching … The “DEBtox” concept toxicokinetics DEB model

internal concentration in time DEB parameters in time external concentration (in time) The “DEBtox” concept toxicokinetics repro growth DEB model survival feeding hatching … DEB parameter cannot be measured … Internal concentration are often not measured …

“Standard” tests ... model parameters for toxicant mechanistic model for species A model parameters for species constant exposure, ad libitum food Many DEBtox examples, e.g.: http://www.bio.vu.nl/thb/users/tjalling

Dynamic exposure model parameters for toxicant mechanistic model for species A 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)

Body length Cumulative offspring Fraction surviving High food Low food Pulse exposure mode of action: ‘assimilation’ • Insights • parameters independent of food • chemical effects fully reversible • reproduction rate slows down …

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 • 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 a community mechanistic model for species B

Community level Food web models can become rather complex … • 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 light producer consumer detritus predator decomposer

Using the DEB community previous project at VU-ThB (EU-MODELKEY) collaboration with SCK-CEN, Belgium (EU-STAR) nutrients light producer consumer detritus predator decomposer

Using the DEB community previous collaborations, e.g., Univ. Antwerp (EU-NoMiracle, EU-OSIRIS) collaboration with UFZ, Leipzig (EU-CREAM) nutrients light producer consumer detritus predator decomposer

Using the DEB community collaboration with Eawag, Switzerland (EU-CREAM) collaboration with IRSN, France nutrients light producer consumer detritus predator decomposer

Using the DEB community previous projects at VU-ThB nutrients light producer consumer detritus predator decomposer

Work needed For the community level • specify interactions between the species • code a community with DEB populations • simulations for various scenarios Evaluate • 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! • 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 • 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 • 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

Wrapping up This project tries to deliver “proof of concept” • 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!

TPT body length cumulative offspring time time Ex.1: maintenance costs Jager et al. (2004)

Pentachlorobenzene body length cumulative offspring time time Ex.2: growth costs Alda Álvarez et al. (2006)

Chlorpyrifos body length cumulative offspring time time Ex.3: egg costs Jager et al. (2007)

Time is of the essence!