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Chemical (and other) stress in DEB 5: extrapolations

Chemical (and other) stress in DEB 5: extrapolations. Tjalling Jager Dept. Theoretical Biology. TexPoint fonts used in EMF. Read the TexPoint manual before you delete this box.: A A A A A A A. Contents. Extrapolations Why extrapolation? Examples of extrapolation. Why extrapolation.

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Chemical (and other) stress in DEB 5: extrapolations

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  1. Chemical (and other) stress in DEB5: extrapolations Tjalling Jager Dept. Theoretical Biology TexPoint fonts used in EMF. Read the TexPoint manual before you delete this box.: AAAAAAA

  2. Contents Extrapolations • Why extrapolation? • Examples of extrapolation

  3. Why extrapolation “Protection goal” Available data ?? • different exposure time • different temperature • different species • time-varying exposure • species interactions • populations • other stresses • mixture toxicity • …

  4. Contents Example life-cycle dataset • Bindesbøl et al (2007), re-analysed in Jager and Klok (2010) • copper in Dendrobaena octaedra • size, survival, cocoons over 20 weeks • here, only [Cu] > 80 mg/kg

  5. 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) DEB analysis of data Assumption • copper leads to a decrease in ingestion rate 80 80 120 120 160 160 200 200 Jager and Klok, 2010

  6. internal concentration in time DEB parameters in time external concentration (in time) Parameter estimates TK pars tox pars DEB pars toxico- kinetics DEB model life-history traits to population model …

  7. Population effects • Type of information that risk assessors should be most interested in ... • Popular endpoints • intrinsic rate of increase • toxicant concentration where this rate is zero • (or multiplication factor lambda, and where it is one) • Popular (simple) approaches • matrix models • Euler-Lotka equation • ...

  8. Matrix models • In combination with DEB(tox) • Klok & De Roos (1996), Lopes et al (2005), Klanjscek et al (2006), Smit et al (2006), Liao et al (2006) • Discrete time and discrete stages ... • one state variable (size or age) for the organism … • DEB generally requires more ... 1 2 3 4

  9. Euler-Lotka equation • In combination with DEB(tox) • Kooijman & Metz (1984), Jager et al (2004), Alda Álvarez et al (2005, 2006) ... • Continuous time and continuous states ... • straightforward for DEB animals • only for constant environment ... • In constant environment, populations grow exponentially

  10. Individual-based models • Follow all individuals seperately … • Full flexibility for dynamic environments • but calculation intensive … • see Martin et al (subm.) Kooijman (2000)

  11. no-effects Population effects But, this is extinction at: • abundant food • no predation • no disease • optimal temperature • low competition • … 0.025 0.02 0.015 population growth rate (d-1) 0.01 0.005 0 60 80 100 120 140 160 180 200 concentration (mg/kg soil) Jager and Klok, 2010

  12. internal concentration in time DEB parameters in time external concentration (in time) Extrapolation: food TK pars tox pars DEB pars toxico- kinetics DEB model life-history traits less food in environment

  13. feeding 5% reproduction maturation maintenance Energy budget … ad libitum growth

  14. reproduction 50% maintenance Energy budget … feeding limiting maturation growth

  15. Food limitation (90%) 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) 80 80 120 120 160 160 200 200

  16. Food limitation 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 and Klok, 2010

  17. internal concentration in time DEB parameters in time external concentration (in time) Extrapolation: chemicals TK pars tox pars DEB pars toxico- kinetics DEB model life-history traits other compounds (related)

  18. Process-based QSAR Jager and Kooijman, 2009

  19. internal concentration in time internal concentration in time DEB parameters in time external concentration (in time) external concentration (in time) toxico- kinetics Extrapolation: mixtures TK pars tox pars DEB pars toxico- kinetics DEB model life-history traits other compounds (mixtures)

  20. internal concentration A in time internal concentration B in time DEB parameters in time external concentration B (in time) external concentration A (in time) Mixtures toxico- kinetics growth DEB model toxico- kinetics life-history traits theory implies interactions …

  21. internal concentration A in time internal concentration B in time DEB parameters in time external concentration A (in time) external concentration B (in time) Mixtures ?? toxico- kinetics DEB model toxico- kinetics life-history traits

  22. compound ‘target’ metabolic process assimilation maintenance … Simple mixture rules toxicity parameters linked (compare CA)

  23. Simple mixture rules compound ‘target’ metabolic process assimilation maintenance …

  24. Simple mixture rules compound ‘target’ metabolic process assimilation maintenance … toxicity parameters independent (compare IA)

  25. Visual representation • For binary mixture, model represents surface that changes in time … Baas et al (2007)

  26. fluoranthene pyrene PAHs in Daphnia • Based on standard 21-day OECD test • 10 animals per treatment • length, reproduction and survival every 2 days • no body residues (TK inferred from effects) Jager et al (2010)

  27. same target costs reproduction (and costs growth)

  28. Iso-effect lines for body length <50% effect

  29. internal concentration in time DEB parameters in time external concentration (in time) Extrapolation: species ? TK pars tox pars DEB pars toxico- kinetics DEB model life-history traits other (related) species

  30. Experiments nematodes Species • Caenorhabditis elegans and Acrobeloides nanus Chemicals • cadmium, pentachlorobenzene and carbendazim Exposure • in agar Endpoints • survival, body size, reproduction over full life cycle • analysed with extended DEBtox Studies published as: Alda Álvarez et al., 2005 (Func. Ecol.), 2006 (ES&T), 2006 (ET&C)

  31. A. nanus PeCB in A. nanus Effects on assimilation

  32. C. elegans PeCB in C. elegans Costs for growth and reproduction

  33. Physiological MoA

  34. Physiological MoA

  35. Physiological MoA

  36. Physiological MoA

  37. toxicant target site toxicant target site maintenance maintenance reproduction reproduction … … Species differences? Species A Species B

  38. Species differences? toxicant target site maintenance reproduction …

  39. internal concentration in time metabolic processes in time external concentration (in time) Extrapolation: exposure TK pars tox pars DEB pars toxico- kinetics DEB model life-history traits time-varying concentrations

  40. Time-varying exposure Specifically relevant for risk assessment • Such as: • accidental spills • plant-protection products • industrial chemicals; batch production • Impractical and costly to test each scenario experimentally

  41. pesticide fate modelling oil-spill modelling Fate modelling

  42. environ. conc. time Time-varying exposure

  43. environ. conc. time time Time-varying exposure Assumption • toxicokinetics follows first-order, one-comp. model internal conc.

  44. environ. conc. NEC time time Time-varying exposure Assumption • effects on energetic processes are reversible blank value assimilation eff. internal conc.

  45. cumul. reproduction body length time time Time-varying exposure

  46. Experimental validation 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)

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

  48. Summary • Extrapolation is crucial for environmental management • extrapolation requires mechanistic theory • DEB provides a framework for extrapolation • But, hypotheses for toxicant effects must be ‘correct’ • More work is needed, e.g., • starvation responses and interaction with toxicants • patterns in DEB parameter values between species • patterns in toxicity parameters (species and chemicals) • reversibility of toxic effects • interactions between chemicals in a mixture • etc. etc. ...

  49. biochemistry DEB theory species specific Outlook • number of chemicals and species is very large … • but number of target sites and DEB parameters is limited! toxicant target site DEB parameters DEB model ? effect on life cycle

  50. Advertisement Vacancies • PhD position at SCK-CEN in Mol (Belgium): radiation effects on duckweed (Lemna minor) with DEB More information: http://www.bio.vu.nl/thb And:http://www.bio.vu.nl/thb/users/tjalling/debtox_papers.htm Also, check out: http://cream-itn.eu/

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