From molecules to populations energy budgets in the causality of toxic effects
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Transcript of From molecules to populations energy budgets in the causality of toxic effects
From molecules to populations
energy budgets in the causality of toxic effects
Tjalling JagerDept. Theoretical Biology
Dept. Theoretical Biology
Aim: ‘Quantitative bioenergetics’
Dept. Theoretical Biology
Aim: ‘Quantitative bioenergetics’
Head of dept.: Prof. Bas Kooijman Permanent staff: Dr. Bob Kooi and Dr. Tjalling Jager PhD students in Amsterdam:
• Jan Baas : NoMiracle, mixture toxicity• Daniel Bontje : ModelKey, food-chain toxicity• Anne Willem Omta : organic carbon pump• Jorn Bruggeman : organic carbon pump• George van Voorn : bifurcation analysis
Causality
How to link toxicant concentrations to whole-organism and population effects?
toxicant
effects onindividual/population
NOEC/ECx
MoA
energy budgets
CBR
Precondition 1
All concepts in causality chain should explicitly consider exposure time
Toxicity is a process in time
• uptake into organism takes time
• biomarker responses can/will change in time
• NOEC/ECx/CBR values can/will change in time
Cl
Cl
Cl Cl
Cl
EC10 in time
Alda Álvarez et al. (2006)
carbendazim
time
pentachlorobenzene
time
survival
body length
cumul. repro
body length
cumul. repro
con
cen
trat
ion
Precondition 2
Causality chain should cover all life-history aspects
Feeding, development, growth and reproduction are linked …
• NOEC/ECx/CBR differ between endpoints
• what about molecular mechanism of action?
Cl
Cl
Cl Cl
Cl
‘Narcotic’ effects
time
EC
10
time
body sizebody size
reproductionreproduction
A. nanus
C. elegans
Cl
Cl
Cl Cl
Cl
Causality of effects
toxicantstatistics e.g., NOEC/ECx
effects onindividual/population
Causality of effects
target sitetoxicant
molecular mechanism
effects onindividual/population
CBRs etc.
Causality of effects
ENERGYBUDGET
rest of the organismtarget sitetoxicant
molecular mechanism
physiological mechanism
effects onindividual/population
Energy budgets
Energy budgets
growth
reproduction
assimilation
Each ‘MoA’ has specific effects
on life cycle(direct/indirect)
Each ‘MoA’ has specific effects
on life cycle(direct/indirect)
maintenance
reproduction
DEB theory
growthmaintenance
assimilation
Kooijman (2000)
(first edition 1993)
DEB theory
Kooijman (2000)
(first edition 1993)
Quantitative theory; ‘first principles’• time, energy and mass balance
Life-cycle of the individual• links levels of organisation: molecule
ecosystems
Fundamental, but practical applications• bioproduction, biodegradation, (eco)toxicity,
sewage treatment, climate change, …
DEB allocation rules
food faeces
reserves
assimilation
structure
somatic maintenance
1-
maturityoffspring
maturity maintenance
DEB model
Toxicants: DEBtox
energy-budgetparameter
toxicokinetics
Life-cycle effectsKooijman & Bedaux, 1996 (Wat. Res.)Jager et al., 2006 (Ecotoxicology)
food faecesfood faeces
reservesreserves
assimilationassimilation
structure
somatic maintenance
structure
somatic maintenance
1- 1-
maturityoffspring
maturity maintenance
maturityoffspring
maturity maintenance
Target: maintenance
time
cum
ula
tive
off
spri
ng
time
bo
dy
len
gth
triphenyltin
Crommentuijn et al. (1997), Jager et al. (2004)
Target: costs for growth
time
bo
dy
len
gth
time
cum
ula
tive
off
spri
ng pentachlorobenzene
Alda Álvarez et al. (2006)
Target: hazard to embryo
time
cum
ula
tive
off
spri
ng
time
bo
dy
len
gth
Chlorpyrifos
Crommentuijn et al. (1997), Jager et al. (2007)
‘Non-toxicant’ effects
food faeces
reserves
structure maturityoffspring
maturity maintenancesomatic maintenance
assimilation
1-
‘Gigantism’• parasites in snails and Daphnia
Decreased size at maturity• parasites and kairomones in Daphnia
Gorbushin and Levakin (1999)
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
Alda Álvarez et al., 2005 (Func. Ecol.), 2006 (ES&T), 2006 (ET&C)
0 2 4 6 8 10 12 14 160
100
200
300
400
500
600
0 5 10 15 20 250
0.2
0.4
0.6
0.8
1
0 2 4 6 8 10 12 14 160
100
200
300
400
500
600
0 2 4 6 8 10 12 14 160
100
200
300
400
500
600
0 5 10 15 20 250
0.2
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0.6
0.8
1
0 5 10 15 20 250
0.2
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1
0 2 4 6 8 10 120
20
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140
0 2 4 6 8 10 120
20
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140
0 2 4 6 8 10 120
20
40
60
80
100
120
140
0 2 4 6 8 10 120
20
40
60
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100
120
140
length
length
eggs
survival
C. elegans and cadmium
Mode of action: assimilation
Alda Álvarez et al. (2005)time (days)
0 10 20 30 40 50 60 70
0
0.1
0.2
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0.4
0.5
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1fr
actio
n su
rviv
ing
0 10 20 30 40 50 60 700
0.1
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1fr
actio
n su
rviv
ing
0 5 10 15 20 25 30 3515
20
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bod
y le
ngth
(µ
m)
0 5 10 15 20 25 30 3515
20
25
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bod
y le
ngth
(µ
m)
0 10 20 30 40 50 600
50
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time (days)
cum
ulat
ive
offs
prin
g pe
r fe
mal
e 02681012
0 10 20 30 40 50 600
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time (days)
cum
ulat
ive
offs
prin
g pe
r fe
mal
e 02681012
02681012
A. nanus and cadmium
Mode of action: costs for growth
Alda Álvarez et al. (2006)
Physiological MoA
C. elegans A. nanus
PeCB(narcotic)
Cadmium(heavy metal)
Carbendazim(inhibits mitosis)
Physiological MoA
C. elegans A. nanus
PeCB(narcotic)
costs for growth and reproduction
assimilation
Cadmium(heavy metal)
Carbendazim(inhibits mitosis)
Physiological MoA
C. elegans A. nanus
PeCB(narcotic)
costs for growth and reproduction
assimilation
Cadmium(heavy metal)
assimilation costs for growth
(+ ageing)
Carbendazim(inhibits mitosis)
Physiological MoA
C. elegans A. nanus
PeCB(narcotic)
costs for growth and reproduction
assimilation
Cadmium(heavy metal)
assimilation costs for growth
(+ ageing)
Carbendazim(inhibits mitosis)
assimilation assimilation
(- ageing)
Population consequences
growth
reproduction
assimilation
maintenance
Population consequences
Population consequences
Population consequences
Each ‘MoA’ has specific effects for populations
Each ‘MoA’ has specific effects for populations
assimilation
reproduction
growthmaintenance
Extrapolate to populations
Constant environment: populations grow exponentially
• ‘intrinsic rate of increase’• calculate from reproduction and survival in time
2 4 6 8 10 120
0
0.2
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0.8
1
concentration (mg/L)2 4 6 8 10 12
concentration (mg/L)0
0
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2 4 6 8 10 1200
0.1
0.2
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00
0.1
0.2
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intr
ins
ic r
ate
(d-1)
Extrapolate to populations
95%
90%
95%90%Mode of action:
assimilation
Mode of action: assimilation
Mode of action: costs for growth
Mode of action: costs for growth
Cadmium
Conclusions
Simple summary statistics are quite useless …• NOEC/ECx change in time and differ between endpoints• not helpful to derive CBRs on basis of ECx
Molecular mechanism is important, but …• not enough to explain effects on life cycle/population
Energy budgets must be considered• direct link to life-history and population effects• cover direct and indirect effects
target sitetoxicant phys. process
effect onlife cycle/population
maintenance
reproduction
…
Outlook
?
Collaboration with CEH Monks Wood life-cycle experiments with C. elegans DEBtox analysis and micro-array work
target sitetoxicant phys. process
effect onlife cycle/population
maintenance
reproduction
…
Outlook
?
Why useful? number of chemicals and species is very large … but number of target sites and processes is limited!
www.bio.vu.nl/thbwww.bio.vu.nl/thb