Tjalling Jager Dept. Theoretical Biology Assessing ecotoxicological effects on a mechanistic basis the central role of the individual

Tjalling Jager Dept. Theoretical Biology Predicting environmental risk A road map for the future

Contents  What’s wrong in risk assessment?  Use ‘molecule-to-ecosystem’ to fix it?  What is the role of the ‘individual’?  A new paradigm … exposure assessment risk effects assessment

Contents  What’s wrong in risk assessment? exposure assessment risk effects assessment

time-varying concentrations Exposure assessment mechanistic fate model mechanistic fate model theory environment phys-chem properties release scenario

Effects assessment statistics ‘safe’ concentration toxicity test arbitrary factors Standardised: exposure time test conditions species/endpoint constant exposure

Risk assessment? mechanistic fate model mechanistic fate model time-varying concentrations statistics & safety factors statistics & safety factors ‘safe’ concentration standard test protocols

mechanistic effects model Risk assessment? theory mechanistic fate model mechanistic fate model time-varying concentrations

Levels of organisation  RA is concerned with impacts on systems … mechanistic effects model

Levels of organisation ecological relevance experimental testing Practical advantages amenable to testing direct ecological relevance

Levels of organisation growth reproduction etcetera food Clear boundaries mass/energy conservation

Levels of organisation biotransformation elimination uptake etcetera Clear boundaries mass/energy conservation

How to build models? toxico-dynamic model toxico-dynamic model toxico-kinetic model toxico-kinetic model exposure pattern effects over time reproduction growth food maintenance development storage

toxico-dynamic model toxico-dynamic model toxico-kinetic model toxico-kinetic model exposure pattern effects over time How to build models? reproduction growth food maintenance development storage Dynamic Energy Budget mass/energy conservation over entire life cycle

Standard DEB animal foodfaeces assimilation reserve

Standard DEB animal structure foodfaeces somatic maintenance assimilation  1-  growth reserve mobilisation

Standard DEB animal structure foodfaeces maturity maintenancesomatic maintenance assimilation  1-  growth reproduction maturity buffer maturation reserve mobilisation eggs p

Example Dendrobaena octaedra and Cu Jager & Klok (2010) Effect on assimilation 80 mg/kg 120 mg/kg 160 mg/kg 200 mg/kg

Extrapolate ‘up’  Energy budget provides: –consistent life-history traits –as function of the environment  Simple link to existing population models

Extrapolate ‘up’  Euler-Lotka equation –in a constant environment, all populations grow exponentially …

Extrapolate ‘up’  Using the calibrated earthworm model … Jager & Klok (2010)

Extrapolate ‘up’  Using the calibrated earthworm model … –predict growth in other constant environments concentration (mg/kg soil) population growth rate (d -1 ) food 100% food 90% Jager & Klok (2010)

Individual-based models DEB-IBM, Martin et al. (2012)  Every individual is a DEB individual –stochasticity through mortality and feeding  Advantages –interaction with food, time-varying conditions –species differ mainly in parameter values …

DEB meets IBM  Calibrate model for Daphnia magna –performance at different constant food levels Martin et al. (2013a)

DEB meets IBM Martin et al. (2013a)  Good prediction of control dynamics –starvation and recovery model essential TotalNeonates JuvenilesAdults

DEB meets IBM  Using standard toxtest to predict population effects Martin et al. (2013b)

Extrapolate ‘up’  Energy budget provides link to population models –Euler-Lotka and IBMs are suitable candidate  Can we continue this to ecosystem level?  How to utilise ‘down’?

‘Adverse outcome pathway’ target site internal toxicant external toxicant toxicokinetics physiological processes maintenance assimilation … effects on traits energy budgetbiochemistry/-omics Human toxicology one species lot’s of funding focus on individual health Yang et al (2004)

‘Adverse outcome pathway’ internal toxicant physiological processes maintenance assimilation … external toxicant toxicokineticsenergy budget In the meantime … knowledge to reduce animal testing –quantify model parameters in vitro –extrapolate between species/chemicals To what extent can we simplify? biochemistry/-omics ? effects on traits life-cycle testing

Old paradigm exposure assessment risk effects assessment

New paradigm exposure assessment risk effects assessment

predicted ‘impacts’ over time mechanistic fate model mechanistic fate model New paradigm model parameters mechanistic individual model(s) population+ ecosystem models environment dedicated testing

Final words  We need mechanistic models for effects –to link fate models to environmental impacts –move away from descriptive statistics  Individual as central level of organisation –energy budget is an essential element –interaction between traits and with environment  Much more work is needed …. –collaboration across disciplines –focus on simplified mechanisms –focus on generality

Thanks for funding IMS (204023/E40) OAPPI (215589) ENERGYBAR (225314/E40) CREAM (PITN-GA ) More info on DEB: (2015 course, Marseille, FR) on DEBtox: (2016 summercourse, DK)

Caenorhabditis elegans toxico-dynamic model toxico-dynamic model toxico-kinetic model toxico-kinetic model exposure pattern growth/repro over time  Exposed to various chemicals –life-history traits –gene expression (transcriptional profiling) Swain et al (2010), Wren et al (2011) affected process affected process

Caenorhabditis elegans maintenance costs 12 h after start repro enrichment of genes associated with DNA integrity and repair … enrichment of genes associated with DNA integrity and repair … Swain et al (2010), Wren et al (2011)

biomarker over time Calanus finmarchicus  Exposed to marine diesel –TKTD model for survival (‘GUTS’) –link biomarker response (GST) toxico-dynamic model toxico-dynamic model toxico-kinetic model toxico-kinetic model exposure pattern survival over time Jager & Hansen (2013)

Calanus finmarchicus toxico-dynamic model toxico-dynamic model toxico-kinetic model toxico-kinetic model exposure pattern survival over time Jager & Hansen (2013) biomarker over time