1. Correlating impacts on life history aspects Bas Kooijman Dept of Theoretical Biology Vrije Universiteit, Amsterdam http://www.bio.vu.nl/thb/deb/ Praha, 2004/04/18 adult embryo juvenile In the context of the Dynamic Energy Budget theory

2. Effects on organisms Process-based perspective on disturbances chemicals, temperature, parasites, noise exposure-time explicit methods (response surface) Primary target: individuals some effects at sub-organismic level can be compensated Effects on populations derived from individuals energy budget basic to population dynamics Parameters of budget model individual specific and (partly) under genetic control

3. Concentration ranges of chemicals too little def: decrease in concentration comes with increase in effects enough def: variations in concentration within this range hardly affect physiological behaviour of individuals too much def: increase in concentration comes with increase in effects e.g. concentration of water can be too much, even for fish no basic difference between toxic and non-toxic chemicals “too little” and “enough” can have zero range for some chemicals Implication: lower & upper NEC for each compound

4. Do No Effect Concentrations exist? Essential component: compensation at individual level Each molecule of any compound has an effect at the molecular level These effects do not necessarily translate into measurable effects at the individual level Example: removal of a kidney in a healthy human body does not result in health effects under conditions that are not extreme NEC is specific for species and chemical compound endpoint (survival, reproduction) one process (maintenance, reproduction,..) is most sensitive experimental/environmental conditions

5. Behaviour  Energetics DEB fouraging module: time budgeting Fouraging: searching, feeding, digestion, food selection feeding  surface area (intra-species), volume (inter-species) Sleeping: repair of damage by free radicals  respiration respiration scales between surface area & volume Social interaction: feeding efficiency (schooling) resource partitioning (territory), parental care mate selection (gene quality  energetic parameter values) Migration: traveling speed and distance: body size related spatial pattern in resource dynamics (seasonal effects) environmental constraints on reproduction

6. Modes of Action of Noise Effects on reproduction blocking out fouraging time reduction feeding efficiency disrupting social behaviour short/long term, partner choice Effects on survival problems with orientation (migration) permanent hearing damage interaction with large-scale fishing

7. Effects of parasites Many parasites increase allocation to som maintenance + growth (chemical manipulation) harvest (all) allocation to develop. + reprod. Results larger body size  higher food intake reduced reproduction

8. Models for toxic effects Three model components: kinetics external concentration  internal concentration example: one-compartment kinetics change in target parameter(s) internal concentration  value of target parameter(s) example: linear relationship physiology value of parameter  endpoint (survival, reproduction) example: DEB model

9. Kinetics Simplest basis: one compartment kinetics Correct for changes in body size (growth) lipid content (starvation) concentration (transformation)

10. Dilution by growth Note: elimination rate decreases with length of isomorph exchange is across surface area small changes in size already affect kinetics considerably

11. Dilution by growth k e /r B ratio internal/external conc tr B 10 2 1 0.5 0.1 2 1 0.5 0.1 scaled body length of daphnid scaled reproduction rate k e elimination rate r B von Bert. growth rate

12. Change in lipid content Note: biomass should be decomposed into reserve & structure applies for slowly changing food densities only

13. Satiating excretion kinetics Elimination rate satiates as function of internal concentration Example: Removal of alcohol from blood by liver

14. Receptor mediated effects Compound knocks out functional receptors Total amount of receptors is constant Hazard rate linear in non-functional receptors : no memory

15. Tasks of physiological module in the specification of toxic effects of chemicals identify potential target parameters for toxic effects (e.g. max feeding rate, specific maintenance and growth costs) specify interrelationships between the various physiological processes (e.g. feeding, maintenance, maturation, growth, reproduction) quantify how endpoints depend on values of target parameters (e.g. how does cumulative number of offspring depend on the specific growth costs?)

16. Basic DEB scheme foodfaeces reserves growth somatic maintenance assimilation 

17. Basic DEB scheme foodfaeces reserves growth maturation reproduction maturity maintenancesomatic maintenance assimilation  1- 

18. Modes of Action of toxicants foodfaeces reserves growth maturation reproduction maturity maintenancesomatic maintenance assimilation  1-    assimilation   maintenance costs   growth costs   reproduction costs   hazard to embryo Lethal effects: hazard rate Mode of action affects translation to pop level

19. Simplest basis: Change  internal conc that exceeds internal NEC or with Change in target parameter Rationale effective molecules operate independently approximation for small effects

20. Hazard rate Definition: instantaneous death rate (dim: time -1 ) Interpretation of hazard rate times time increment: probability of death, given to be alive Relationship with survival probability for : Examples for :

21. Independent causes of death If causes of death by events 0 are independent of that by events 1 then hazard rate add and survival probabilities multiply Example of application: death by background mortality and by toxicant in short bioassays: background mortality is accidental which means that the hazard rate is constant

22. Effect on survival Effects of Dieldrin on survival of Poecilia killing rate 0.038 l  g -1 d -1 elimination rate 0.712 d -1 NEC 4.49  g l -1

23. DEB-based effects on body growth Indirect effects indicator: effects on ultimate size at constant food decrease of assimilation rate (food intake, digestion) increase of specific maintenance costs Direct effects indicator: no effects on ultimate size at constant food increase of costs for synthesis of biomass (structural)

24. Effect on assimilation CuCl 2 mg/kgtime, d weight 1/3, mg 1/3 Data from Klok & de Roos 1996 NEC = 4.45 mg CuCl2 /kg on Lumbricus rubellus

25. DEB-based effects on reproduction Indirect effects indicator: effects on onset of reproduction decrease of assimilation rate (food intake, digestion) increase of specific maintenance costs increase of costs for synthesis of biomass (structural) Direct effects indicator: no effects on onset of reproduction increase of costs for the synthesis of offspring decrease of survival probability at birth

26. Direct effect on reproduction time, d cum. # young/female 0 0.2 0.4 0.8 1 2  g Cd/l Effect on hazard NEC = 0.023  g Cd/l

27. energetics growth maintenance Free radicals and ageing Respiration Oxidative damage free radicals (internally generated) survival feeding tumour induction

28. Tumour inducing compounds Mode of action: genotoxic compounds: similar to (natural) free radicals enhance aging non-genotoxic compounds: hamper cell-cell communication Tumour growth dynamics similar to growth of body parts  -rule for allocation of resources in DEB context growth depends on: physiology via nutrition (feeding conditions) body size (age): fast growth at young age Leeuwen, I. M. M. van 2003 Mathematical models in cancer risk assessment PhD-thesis, Vrije Universteit Amsterdam

29. Effect Concentration ECx(t): Concentration that gives x% effect at exposure time t, compared to the blank LCx(t) = ECx(t) in the case the endpoint is the survival probability (LC = lethal concentration) Generally: ECx(t) decreases in time the pattern depends on the properties of the chemical and of the test organism NEC = EC0(  )

30. Fast kinetics Effects on survival at instantaneous equilibrium

31. Effects on populations At constant food density: At variable food density: individual-based modelling of populations requires modelling of resources

32. Population effects can depend on food density Population growth of rotifer Brachionus rubens at 20˚C for different algal concentrations 3,4-dichloroaniline direct effect on reproduction potassium metavanadate effect on maintenance

33. 0 number of daphnids Maintenance first 10 6 cells.day -1 300 200 100 0 1206030126 max number of daphnids 30 35 400 300 200 100 81115182124283237 time, d 30  10 6 cells.day -1 Chlorella-fed batch cultures of Daphnia magna, 20°C neonates at 0 d: 10 winter eggs at 37 d: 0, 0, 1, 3, 1, 38 Kooijman, 1985 Toxicity at population level. In: Cairns, J. (ed) Multispecies toxicity testing. Pergamon Press, New York, pp 143 - 164 Maitenance requirements: 6 cells.sec -1.daphnid -1

34. Food intake at carrying capacity 10 3 cells/daphnid.d log mg V/l log mg Br/llog mg DMQ/l log mg K 2 Cr 2 O 7 /l log mg AA/llog mg Col/l 9-aminoacridine colchicine 2,6-dimethylquinoline sodium bromidemetavanadate potassium dichromate