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Biology-based approaches for mixture ecotoxicology

Biology-based approaches for mixture ecotoxicology. Tjalling Jager. Contents. 14:00-18:00 (coffee at 16:00) Lecture limitations of descriptive approaches framework for a process-based approach Dynamic Energy Budget (DEB) theory sub-lethal effects

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Biology-based approaches for mixture ecotoxicology

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  1. Biology-based approaches for mixture ecotoxicology Tjalling Jager

  2. Contents 14:00-18:00 (coffee at 16:00) • Lecture • limitations of descriptive approaches • framework for a process-based approach • Dynamic Energy Budget (DEB) theory • sub-lethal effects • simplified survival modelling in more detail • Practical exercise • Play with a “toy model” in Excel (survival only) 18:00-18:30 Open discussion

  3. your mixture data full data interpretation Disclaimer! X Process-Based Model

  4. Interest in mixtures • Scientific • why are effects of mixtures the way they are? • Practical • how can we predict the environmental impact of mixtures?

  5. Practical challenge • Some 100,000 man-made chemicals • Large range of natural toxicants • For animals alone, >1 million species described • Complex exposure situations

  6. Typical approach A B

  7. Typical approach

  8. Typical approach

  9. Typical approach wait for 21 days …

  10. total offspring concentration B concentration A Dose-response plot dose-ratio dependent deviation from CA

  11. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?”

  12. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?”

  13. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?”

  14. What question did we answer? “What is effect of constant exposure to this mixture on totalDaphnia reproduction after 21 days under standard OECD test conditions?”

  15. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?”

  16. What question did we answer? “What is effect of constant exposure to this mixture on total Daphniareproduction after 21 days under standard OECD test conditions?”

  17. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?”

  18. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?”

  19. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?” Relevance for science?

  20. Why! What question did we answer? “What is effect of constant exposure to this mixture on Daphnia reproduction after 21 days under standard OECD test conditions?” Relevance for science?

  21. What question did we answer? “What is effect of constant exposure to this mixture on total Daphnia reproduction after 21 days under standard OECD test conditions?” Relevance for risk assessment?

  22. Better questions Why do we see: • time patterns of effects on different endpoints …

  23. survival pentachlorobenzene body length 140 cumul. reproduction 120 100 80 60 40 20 0 0 0 5 10 15 20 0 2 4 6 8 10 12 14 16 time (days) EC10 in time Alda Álvarez et al. (2006) carbendazim 2.5 2 1.5 1 0.5 time (days)

  24. Dry weight Reproduction Cd and Zn in springtails Van Gestel & Hensbergen (1997) 5 4 TU = 1 3 TU mixture 50% effect, internal concentration 2 1 0 0 1 2 3 4 5 6 time (weeks)

  25. Better questions Why do we see: • time patterns of effects on different endpoints … • interactions between compounds and with environment … • differences between species and between compounds … • can we make useful predictions for risky situations?

  26. external concentration B (in time) external concentration A (in time) effects in time Process-based Assumption: internal concentration is linked to the effect causility

  27. toxico- kinetics internal concentration A in time internal concentration B in time external concentration B (in time) external concentration A (in time) effects in time toxico- kinetics Process-based Assumption: internal concentration is linked to the effect “toxicodynamic animal model”

  28. Demands on toxicokinetics model • Complexity should match the level of detail in data • simplest: scaled one-compartment model • one parameter (elimination rate) • estimated from effects data only • most complex: PBPK model … • requires detailed measurements … toxico- kinetics

  29. Demands on animal model • Explain endpoints of interest over entire life cycle • growth, start of reproduction, reproduction rate, survival, … • Explain effects of toxicants on these endpoints • Allow to interpret effects of multiple stressors • combination of chemicals • chemicals and non-chemical stressors • As little chemical- and species-specific as possible • comparison and extrapolation All organisms obey conservation of mass and energy! “toxicodynamic animal model”

  30. Look closer at individual

  31. Look closer at individual

  32. Look closer at individual

  33. Look closer at individual

  34. Look closer at individual

  35. Natural role for energetics Understanding toxic effects on growth and reproduction requires understanding how food is acquired and used to produce traits • Rules for metabolic organisation • Start of Dynamic Energy Budget (DEB) theory 30 years ago

  36. Kooijman (2000) Kooijman (2010) What is DEB? Quantitative theory for metabolic organisation; ‘first principles’ • time, energy and mass balance Life-cycle of the individual • links levels of organisation: molecule  ecosystems Fundamental; many practical applications • (bio)production, (eco)toxicity, climate change, evolution …

  37. food feces assimilation reserve mobilisation somatic maintenance maturity maintenance  1- maturation reproduction growth structure maturity eggs Standard DEB animal b p

  38. Kooijman (2000)

  39. mobilisation somatic maintenance maturity maintenance  1- maturation reproduction growth structure maturity eggs Standard DEB animal food feces b assimilation reserve p

  40. over entire life cycle internal concentration in time repro DEB parameters in time growth external concentration (in time) survival feeding hatching … Toxicant effects in DEB assimilation maintenance maturation …. toxico- kinetics “toxicodynamic animal model” DEB model Kooijman & Bedaux (1996), Jager et al. (2006, 2010)

  41. internal concentration in time DEB parameters in time external concentration (in time) Toxicant effects in DEB Affected DEB parameter has specific consequences for life cycle toxico- kinetics repro growth DEB model survival feeding hatching …

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

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

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

  45. internal concentration A in time internal concentration B in time DEB parameters in time external concentration A (in time) external concentration B (in time) toxico- kinetics Mixture analysis toxico- kinetics DEB model effects on all endpoints in time theory implies interactions …

  46. toxico- kinetics internal concentration A in time internal concentration B in time DEB parameters in time external concentration A (in time) external concentration B (in time) toxico- kinetics Mixture analysis DEB model effects on all endpoints in time theory implies interactions …

  47. toxico- kinetics internal concentration A in time internal concentration B in time DEB parameters in time external concentration A (in time) external concentration B (in time) toxico- kinetics Mixture analysis growth DEB model effects on all endpoints in time theory implies interactions …

  48. internal concentration A in time internal concentration B in time DEB parameters in time external concentration A (in time) external concentration B (in time) Mixture analysis ?? toxico- kinetics DEB model toxico- kinetics effects on all endpoints in time

  49. DEB parameter maintenance costs ingestion rate growth costs … Simple mixture rules compound ‘target’ toxicity parameters linked (compare CA)

  50. DEB parameter maintenance costs ingestion rate growth costs … Simple mixture rules compound ‘target’

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