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Assessing ecotoxicological effects on a mechanistic basis the central role of the individual

This article discusses the limitations of current risk assessment methods and proposes a new approach that focuses on individual-level effects. It explores the use of mechanistic fate models, exposure assessment, and effects assessment in predicting environmental risk. The article also emphasizes the importance of incorporating ecological relevance and experimental testing in risk assessment.

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Assessing ecotoxicological effects on a mechanistic basis the central role of the individual

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

  2. Predicting environmental riskA road map for the future Tjalling Jager Dept. Theoretical Biology

  3. 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 effects assessment risk

  4. Contents • What’s wrong in risk assessment? exposure assessment effects assessment risk

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

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

  7. Risk assessment? standard test protocols mechanistic fate model statistics & safety factors time-varyingconcentrations ‘safe’ concentration

  8. Risk assessment? theory mechanistic fate model mechanisticeffects model time-varyingconcentrations

  9. Levels of organisation • RA is concerned with impacts on systems … mechanisticeffects model

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

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

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

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

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

  15. Standard DEB animal food faeces assimilation reserve

  16. Standard DEB animal food faeces assimilation reserve mobilisation somatic maintenance  1- growth structure

  17. Standard DEB animal food faeces assimilation reserve mobilisation somatic maintenance maturity maintenance  1- maturation reproduction growth p structure maturity buffer eggs

  18. 40 9 35 8 30 7 25 6 cumulative offspring per female 20 5 body length 15 4 10 3 5 2 0 0 50 100 150 1 time (days) 0 50 100 150 time (days) Example Dendrobaena octaedra and Cu Jager & Klok (2010) Effect on assimilation 80 mg/kg 120 mg/kg 160 mg/kg 200 mg/kg

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

  20. Extrapolate ‘up’ • Euler-Lotka equation • in a constant environment, all populations grow exponentially …

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

  22. Extrapolate ‘up’ • Using the calibrated earthworm model … • predict growth in other constant environments 0.025 0.02 food 100% 0.015 population growth rate (d-1) 0.01 food 90% 0.005 0 60 80 100 120 140 160 180 200 concentration (mg/kg soil) Jager & Klok (2010)

  23. 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 …

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

  25. DEB meets IBM • Good prediction of control dynamics • starvation and recovery model essential Total Neonates Juveniles Adults Martin et al. (2013a)

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

  27. 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’?

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

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

  30. Old paradigm exposure assessment effects assessment risk

  31. New paradigm exposure assessment effects assessment risk

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

  33. 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

  34. Thanks for funding IMS (204023/E40) OAPPI (215589) ENERGYBAR (225314/E40) CREAM (PITN-GA-2009-238148) More info on DEB: www.bio.vu.nl/thb (2015 course, Marseille, FR) on DEBtox: www.debtox.info (2016 summercourse, DK)

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

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

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

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

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