Day 3: sub-lethal effects with DEB3

1. Day 3: sub-lethal effects with DEB3 Full consistency, and full complexity

2. Limits of ‘DEBtox’ To work with standard test data … ‘DEBtox’ applied a simplified DEB model • constant reserve density • constant length at puberty • constant cost for an egg

3. Constant reserve density … food faeces assimilation reserves somatic maintenance maturity maintenance  1- maturity offspring structure

4. Constant length at puberty … food faeces assimilation reserves somatic maintenance maturity maintenance  1- maturity offspring structure

5. Constant egg costs … food faeces assimilation reserves somatic maintenance maturity maintenance  1- maturity offspring structure

6. ‘DEB 3’ • Explicit calculation of maturation • maturity level → hatching and onset reproduction • → maturity maintenance • Explicit calculation of egg costs • may change under (toxic) stress • Disadvantages • data requirements • computations more complex • parameter interpretation Kooijman et al (2008), Kooijman (2010)

7. Energy flows … X P food faeces A=X-P reserves S=kMV J=kJH C G=κC-kMV R=(1-κ)C-kJH maturity offspring structure

8. In equations …

9. DEB3 • This set of equations captures the entire life cycle • thus includes the embryonic development • chemical stress can act on any parameter … • Embryology follows from the basic parameters • so egg costs, hatching time, hatchling size are not model parameters! • All life history “events” are triggered by maturity • hatching (UHb), which is the start of feeding • puberty (UHp), start of reproduction and stop of maturation • pupation in holometabolic insects?

10. reserves somatic maintenance maturity maintenance  1- maturity structure for embryos …

11. food faeces assimilation reserves somatic maintenance maturity maintenance  1- maturity structure for juveniles …

12. food faeces assimilation reserves somatic maintenance maturity maintenance  1- gametes structure periodic release of eggs for adults … reproduction buffer

13. How to calculate embryo? • Egg costs calculated from the basic parameters • Assumption: • at birth, hatchling will have same scaled reserve density (e) as its mother at the time of egg production • this means that egg costs can (and will) change over time! • The DEB3 equations specify embryonic development and thus hatching time and hatchling size • “DEBtool” has efficient routines to calculate this without the need for ODE simulation • DEBtool routines included in DEBtoxM

14. Toxicants and DEB3 Example: • Nematode Acrobeloides nanus • Data from Alda Álvarez et al (2006)

15. 200 65 180 60 160 55 140 50 120 45 cumulative offspring per female 100 body length 40 80 35 60 30 40 25 20 20 0 0 5 10 15 20 15 0 5 10 15 20 25 30 time time Pentachlorobenzene • mode of action: decrease of ingestion rate • allows estimation of all basic parameters • somatic maint. coeff. = maturity maint. coeff.

16. 180 65 160 60 140 55 120 50 100 cumulative offspring per female 45 80 body length 40 60 35 40 30 20 25 0 20 0 5 10 15 20 15 time 0 5 10 15 20 25 30 35 time Cadmium • MoA: increase costs for structure • decrease maturity maintenance? • .

17. 180 65 60 160 55 140 50 120 45 100 cumulative offspring per female body length 40 80 35 60 30 40 25 20 20 0 15 0 5 10 15 20 0 5 10 15 20 25 30 35 time time Cadmium • MoA: increase costs for structure • decrease maturity maintenance? • increase ageing?

18. 65 180 60 160 55 140 50 120 45 100 cumulative offspring per female body length 40 80 35 60 30 40 25 20 20 15 0 0 5 10 15 20 25 30 35 0 5 10 15 20 time time Cadmium • MoA: increase costs for structure • decrease maturity maintenance? • increase ageing?

19. Toxicants and DEB3 • Using DEB3 allows more flexibility • any parameter can be affected by toxicant • fully consistent consequences of effects • but … user-friendliness is decreased • parameters are more difficult to interpret • Pentachlorobenzene versus cadmium • misfits trigger search for most likely mechanism(s) of actions • further research could examine other endpoints, e.g., length at birth (predicted 30% reduction by Cd)

20. Where do we go? DEB 3 allows to address new questions

21. Avenues for further research Challenges opened up by ‘DEB 3’ • DEB3 predicts interaction between toxicants and egg development • e.g., longer development and smaller hatchlings • effects are linked to effects observed on juveniles/adults • Important because: • egg costs determine reproduction rates • hatching time and hatchling size are (probably) essential for population response

22. Scope of PhD project Elke • Broad question: • how do effects at the energy budget propagate to the population level? • Specific questions: • how do toxicants affect embryonic development? • explain these effects from effects on the energy budget? • how important are embryonic effects for the population? • Organism: the pond snail (Lymnaea stagnalis)

23. Avenues for further research Challenges opened up by DEB3 • Consistent analysis when puberty length is affected • e.g., cadmium in some nematodes • compounds that appear to affect kappa … • Increase in kappa results in: • larger ultimate size • first reproduction at larger body size

24. Natural ‘toxicants’ Suspected kappa effects: • Trematodes in snails • Gorbushin and Levakin (1999) • Microsporidian in Daphnia • Chadwick and Little (2005) • Fish infochemicals on Daphnia • Stibor (1992)

25. Natural ‘toxicants’ Man-made endocrine disruptors? • Daphnia and ibuprofen? • Heckmann et al (2007) • Nematodes and nonyl-phenol? • Höss et al (2002)

26. Final words … • Understanding toxic effects requires energy budgets • started DEB development 30 years ago • essential for ecotoxicology and risk assessment • Understanding energy budgets requires toxicants • shed light on e.g., maturation and ageing • often requires DEB3 formulation • Toxicants stress organisms in very specific ways • some 100,000 man-made chemicals registered • plus whole range of natural ‘toxicants’ • However, DEB analyses raise new questions … • modellers must have close links to the lab!

27. DEBtoxM for DEB3

28. More complexity • More parameters, so requires more/better data • or defaults based on size-rules (“add-my-pet”) • Low-level DEB parameters; no more Lm, Rm, etc. • Calculations less robust and more time consuming • some parameter combination are not viable (e.g., L0<Lb) • uses routines from DEBtool to calculate egg costs (programmed in a short-cut manner) • Population calculations are more tricky …

29. time should include hatching! offspring quality may change with age of mother DEB individuals to populations • Toxicants may affect hatching time/quality • Maternal effects: what are the parameters of the offspring; what is their body residue?

30. Disclaimer! • Many of these issues are still open, or are solved in an ad hoc manner • The Matlab version is very much Beta!

31. Extra’s Ageing in DEB models

32. 400 350 7 300 6.5 250 cumulative offspring per female 6 200 5.5 150 5 body length 100 4.5 50 4 0 3.5 0 10 20 30 40 50 3 1 2.5 0 20 40 60 80 100 120 time 0.8 0.6 fraction surviving 0.4 0.2 0 0 10 20 30 40 50 time What is ageing? Jager et al (2004)

33. 3000 2500 7 2000 6.5 cumulative offspring per female 6 1500 5.5 1000 5 body length 4.5 500 4 0 0 20 40 60 80 100 120 3.5 3 2.5 1 0 20 40 60 80 100 120 time 0.8 0.6 fraction surviving 0.4 0.2 0 0 20 40 60 80 100 120 time What is ageing? Jager et al (2004)

34. reserve mobilisation amplification free radicals damage-inducing compunds damage compounds dilution by growth hazard rate dilution by growth Ageing in DEB models • Treated somewhat similar to toxicant effects • Basic idea in DEB3: e.g., changed genes, affected mitochondria e.g., “wrong” proteins

35. Example: guppies caloric restriction

36. Ageing effects on repro? • Still to be investigated in detail! • Observations: • reproduction rate declines with old age • feeding rates decline with old age • body size does not change (much) with old age

37. time (days) Toxicants influence ageing Folsomia candida and cadmium time (days) Jager et al. (2004)

38. Toxicants influence ageing Acrobeloides nanus and carbendazim Alda Álvarez et al. (2006)

39. Avenues for further research • Interaction of ageing and toxicants is still a wide open field • can we understand interactions from simple stress factors on ageing parameters? • The ageing module itself is also open for further investigation!