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Chemical (and other) stress in DEB 1: Introduction

Chemical (and other) stress in DEB 1: Introduction. Tjalling Jager Dept. Theoretical Biology. Lectures on (eco)toxicity. Introduction toxic stress is important (and interesting) logical link to DEB theory brief history of toxic stress in DEB Toxicokinetics

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Chemical (and other) stress in DEB 1: Introduction

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  1. Chemical (and other) stress in DEB1: Introduction Tjalling Jager Dept. Theoretical Biology

  2. Lectures on (eco)toxicity • Introduction • toxic stress is important (and interesting) • logical link to DEB theory • brief history of toxic stress in DEB • Toxicokinetics • uptake and elimination of chemicals in the body • Toxicodynamics and survival • target sites and affected parameters • effects on survival • Sub-lethal effects • case studies, effects on growth and reproduction • Extrapolation • e.g., population effects, time-varying exposure

  3. Which chemicals are toxic? All of them! Paracelsus (1493-1541): “The dose makes the poison” So toxicity is everywhere!

  4. Natural toxicants: elements Metals • e.g., iron, zinc, cadmium • human use: Cd in pigment, stabiliser in plastics, batteries, electroplating • natural occurence: zinc and phosphate ores

  5. Natural toxicants: byproducts Polycyclic Aromatic Hydrocarbons (PAHs) • e.g., phenanthrene, fluoranthene, benzo[a]pyrene • human: cigarette smoke, cooking, combustion of fuel • natural: in oil, coal, and tar deposits, forest fires

  6. Natural toxicants: byproducts Dioxins • e.g., 2,3,7,8-TCDD • human: paper and fiber bleaching, incineration of waste, metal smelting, cigarette smoke • natural: incomplete combustion of chlorine-containing things

  7. Natural toxicants: defense Oleandrin • oleander (Nerium oleander) • gastrointestinal and cardiac effects, skin irritation, CNS effects (coma), death

  8. Natural toxicants: defense Pyrethrin • pyrethrum (Chrysanthemum cinerariaefolium) • neurotoxic and repellent for insects

  9. Natural toxicants: defense Alkaloids • 10-25% of higher plants, ladybirds, poison dart frogs, cinnabar moth, ... • bitter taste, range of metabolic effects, recreational drugs ...

  10. Natural toxicants: competition Juglone • black walnut (Juglans nigra) • respiratory inhibitor for many plant species

  11. Natural toxicants: offense “Venom” • spiders, snakes, cone snails, jellyfish ...

  12. Natural toxicants: utility Nonylphenol • velvet worm (Euperipatoides kanangrensis) • squirts slime that contains nonylphenol • surfactant that is toxic, endocrine disruptor • production and use by humans restricted in EU

  13. Natural toxicants: bacteria Botulinum toxin • botulism (Clostridium botulinum) • powerful neurotoxin (“most toxic compound known”), for cosmetic treatment “botox”

  14. Natural toxicants: infochemicals • Prey respond to chemical cues from predators • life history, morphological, behavioural changes • e.g., helmet and spine in Daphnia lumholtzi • e.g., mice fear the smell of cats

  15. too little ok too much performance concentration To summarise … • Toxicity is inherent to life • all chemicals are toxic (even nutrients) • many species evolved chemicals intended to be toxic • all species evolved mechanisms to deal with excess nutrients and unwanted chemicals

  16. To summarise … • Toxicity is inherent to life • all chemicals are toxic (even nutrients) • many species evolved chemicals intended to be toxic • all species evolved mechanisms to deal with excess nutrients and unwanted chemicals ok too much performance concentration

  17. Human-made toxicants • Wide variety of uses • paints, detergents, solvents, pesticides, pharmaceuticals, polymers, … • probably some 100.000 compounds • Chemical industry is BIG business! • production value 2009: 3.4 trillion dollar (3.400.000.000.000 $) • equals the GDP of Germany • All are toxic, some are intended to kill • fungicides, insecticides, herbicides, nematicides, molluscicides, …

  18. Pesticides in agriculture • In the Netherlands in 2008: • 5.6 million kg a.i. • average 6.9 kg a.i./ha • worst crop: lily bulbs at 99 kg a.i./ha

  19. Human-made vs. natural What is the difference? • Time scale • major increase after second world war • rapid development of new types of molecules • Spatial scale • amounts emitted • landscape and even global instead of local • Since 1970’s, most countries have programmes for environmental protection ...

  20. In 1962 …

  21. Ecotoxicology • Studies the effect of chemical stress • from molecular level to ecosystems • But, in practice focus on • man-made chemicals … • not birds and mammals … • individual level effects ... • environmental risk assessment ... • standardised experimental tests • For example the Daphnia reproduction test • OECD guideline 211

  22. Reproduction test

  23. Reproduction test

  24. Reproduction test

  25. Reproduction test wait for 21 days …

  26. Range of Concentrations

  27. EC50 NOEC Dose-response plot total offspring log concentration

  28. If EC50 is the answer … … what was the question? “What is the concentration of chemical X that leads to 50% effect on the total number of offspring of Daphnia magna (Straus) after 21-day constant exposure under standardised laboratory conditions?” • What does this answer tell me about other situations? • (almost) nothing!

  29. Organisms are complex

  30. Stressing organisms … only adds to the complexity • Response to stress depends on • organism (species, life stage, sex, …) • endpoint (size, reproduction, development, …) • type of stressor (toxicant, radiation, parasites, …) • exposure scenario (pulsed, multiple stress, …) • environmental conditions (temperature, food, …) • etc., etc.

  31. Complexity Environmental chemistry … • predict the concentrations of chemicals in the environment • from emissions and physico-chemical properties

  32. Idealisation • E.g., multimedia-fate or “box” models • mechanistic, mass balance, area:volume

  33. toxicodynamics internal concentration in time external concentration (in time) effects on endpoints in time toxicokinetics TKTD modelling toxico-kinetic model process model for the organism

  34. Simplifying biology? At the level of the individual … • how much biological detail do we minimally need … • to explain how organisms grow, develop and reproduce • to explain effects of stressors on life history • to predict effects for untested situations • without being species- or stressor-specific

  35. Simplifying biology? At the level of the individual … • how much biological detail do we minimally need … • to explain how organisms grow, develop and reproduce • to explain effects of stressors on life history • to predict effects for untested situations • without being species- or stressor-specific • Forget the details and focus on energy budget! • how is food used to fuel the life cycle?

  36. E.g., effect on reproduction

  37. E.g., effect on reproduction

  38. E.g., effect on reproduction

  39. E.g., effect on reproduction

  40. E.g., effect on reproduction • To understand an effect on reproduction … • need to know how food is used to make offspring • and how chemicals interfere with this process

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

  42. Different food densities Jager et al (2005) Zimmer et al (in prep.)

  43. other stressors? food feces b assimilation reserve ? mobilisation somatic maintenance maturity maintenance  1- maturation reproduction growth p structure maturity buffer eggs

  44. parasites, ageing food stress internal concentration in time repro DEB parameters in time growth external concentration (in time) survival feeding hatching … Stressor effects in DEB toxico- kinetics DEB model

  45. internal concentration in time DEB parameters in time external concentration (in time) Stressor effects in DEB toxico- kinetics repro growth DEB model survival feeding hatching … DEB parameter cannot be measured … Internal concentration are often not measured …

  46. A brief history of ‘DEBtox’ Corresponds with origin of DEB in 1979 egg

  47. A brief history of ‘DEBtox’ The 80’s … • Kooijman (1981) • toxicokinetics determines survival pattern • Kooijman & Metz (1984) • toxicants affect energy budgets and thereby population response egg

  48. A brief history of ‘DEBtox’ The early 90’s … • Parallel to OECD trajectory • review test guidelines with respect to statistical analysis • 1996: “analyse time course of effects” and “prefer mechanistic models” egg

  49. A brief history of ‘DEBtox’ Birth in 1996 … • Windows software and booklet (Kooijman & Bedaux, 1996) • Series of papers • Bedaux & Kooijman (1994) • Kooijman & Bedaux (1996) • Kooijman et al (1996)

  50. A brief history of ‘DEBtox’ And 10 years later … • ISO/OECD (2006) • DEBtox next to methods for NOEC and EC50 • ECB workshop (2007) • presenting DEBtox to EU risk assessors

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