Chemical (and other) stress in DEB 1: Introduction Tjalling Jager Dept. Theoretical Biology.
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Transcript of Chemical (and other) stress in DEB 1: Introduction Tjalling Jager Dept. Theoretical Biology.
Lectures on (eco)toxicity
1. Introduction• toxic stress is important (and interesting)
• logical link to DEB theory
• brief history of toxic stress in DEB
2. Toxicokinetics• uptake and elimination of chemicals in the body
3. Toxicodynamics and survival• target sites and affected parameters
• effects on survival
4. Sub-lethal effects• case studies, effects on growth and reproduction
5. Extrapolation• e.g., population effects, time-varying exposure
Which chemicals are toxic?
All of them!
Paracelsus (1493-1541):
“The dose makes the poison”
So toxicity is everywhere!
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
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
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
Natural toxicants: defense
Oleandrin• oleander (Nerium oleander)• gastrointestinal and cardiac effects, skin irritation, CNS
effects (coma), death
Natural toxicants: defense
Pyrethrin• pyrethrum (Chrysanthemum cinerariaefolium)• neurotoxic and repellent for insects
Natural toxicants: defense
Alkaloids• 10-25% of higher plants, ladybirds, poison dart frogs,
cinnabar moth, ...• bitter taste, range of metabolic effects, recreational drugs ...
Natural toxicants: competition
Juglone• black walnut (Juglans nigra)• respiratory inhibitor for many plant species
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
Natural toxicants: bacteria
Botulinum toxin• botulism (Clostridium botulinum)• powerful neurotoxin (“most toxic compound known”), for
cosmetic treatment “botox”
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
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
concentration
too muchoktoo little
perf
orm
ance
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
concentration
too muchok
perf
orm
ance
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, …
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
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 ...
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
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!
EC50EC50
tota
loff
spri
ng
log concentration
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.
Complexity
Environmental chemistry …• predict the concentrations of chemicals in the environment• from emissions and physico-chemical properties
Idealisation
air
water
sediment
naturalsoil
agricult.soil
industr.soil
emission advection diffusion degradation
E.g., multimedia-fate or “box” models• mechanistic, mass balance, area:volume
externalconcentration
(in time)
toxico-kineticmodel
toxico-kineticmodel
TKTD modelling
internalconcentration
in time
process modelfor the organism
process modelfor the organism
effects onendpoints
in timetoxicokinetics
toxicodynamics
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
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?
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
eggs
mobilisation
Standard DEB animal
structurestructure
somatic maintenance
growth
maturity maintenance1-
reproduction
maturitymaturity bufferbuffer
maturation p
food fecesassimilation
reservereserve
b
Different food densities
Jager et al (2005)
0 2 4 6 8 10 1220
30
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time (d)
bo
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gth
(µ
m)
0 2 4 6 8 10 1220
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0 2 4 6 8 10 120
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time (d)
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Zimmer et al (in prep.)
other stressors?
structurestructure
food feces
maturity maintenancesomatic maintenance
assimilation
1-
growth reproduction
maturitymaturity bufferbuffer
maturation
b
p
reservereserve
mobilisation
eggs
?
Stressor effects in DEB
externalconcentration
(in time)
toxico-kinetics
toxico-kinetics internal
concentrationin time DEB
parametersin time
DEBmodel
DEBmodel
repro
growth
survival
feeding
hatching
…
food stress
parasites, ageing
Stressor effects in DEB
externalconcentration
(in time)
toxico-kinetics
toxico-kinetics internal
concentrationin time DEB
parametersin time
DEBmodel
DEBmodel
Internal concentration are often not measured …
repro
growth
survival
feeding
hatching
…DEB parameter cannot be measured …
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
A brief history of ‘DEBtox’
egg
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”
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)
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
eggs
mobilisation
‘DEBtox’ simplification
structurestructure
somatic maintenance
growth
maturity maintenance1-
reproduction
maturity buffer
maturation p
food fecesassimilation
reserve
A brief history of ‘DEBtox’
The 2000’s … Péry et al (2002, 2003)
• modifications for midges
Ducrot et al (2004, 2007)• midges and snails
Lopes et al (2005)• link to matrix models
Billoir et al (2007, 2008)• matrix models, Bayes, new
derivation
Muller et al (2010)• alternative formulation
division
A brief history of ‘DEBtox’
In our group … Jager et al (2004), Alda
Álvarez et al (2005, 2006)• multiple endpoints and
ageing• population (Euler-Lotka)
Baas et al (2007, 2009)• mixtures: lethal effects
division
A brief history of ‘DEBtox’
Embryo division … Klok & De Roos (1996),
Klok et al (1997, 2007)• earthworm matrix model,
Bayesian approach
A brief history of ‘DEBtox’
Applying ‘DEB3’ … Jager et al (2010)
• basis and mixtures
Jager & Klok (2010)• compare methods and
population level
Summary
Toxicants are an integral part of life• difference between natural and man-made is a matter of
time and spatial scale
For effects on life-history traits, DEB follows naturally• food is used to fuel all traits over the life cycle• toxicants affect DEB parameters• should allow extrapolation to untested conditions
Valuable for• environmental risk assessment• teasing rules for metabolic organisation out of a living
system