Tjalling Jager

Dept. Theoretical Biology

Assessing ecotoxicological effects on a mechanistic basis

the central role of the individual

Tjalling Jager

Dept. Theoretical Biology

Predicting environmental risk

A road map for the future

Contents

What’s wrong in risk assessment? Use ‘molecule-to-ecosystem’ to fix it? What is the role of the ‘individual’? A new paradigm …

exposure assessment

risk

effects assessment

Contents

What’s wrong in risk assessment?

exposure assessment

risk

effects assessment

time-varying concentrations

Exposure assessment

mechanisticfate model

mechanisticfate model

theorytheory

environment

phys-chem propertiesrelease scenario

Effects assessment

statisticsstatistics

‘safe’concentration

EC50

resp

on

se

log concentration

toxicity testarbitrary factors

Standardised:•exposure time•test conditions•species/endpoint•constant exposure

Risk assessment?

mechanisticfate model

mechanisticfate model

time-varying concentrations

EC50

resp

on

se

log concentration

statistics &safety factorsstatistics &

safety factors

‘safe’ concentration

standard test protocols

mechanistic effects modelmechanistic

effects model

Risk assessment?

theorytheory

mechanisticfate model

mechanisticfate model

time-varying concentrations

Levels of organisation

RA is concerned with impacts on systems …

mechanistic effects modelmechanistic

effects model

Levels of organisation

ecological relevance

experimental testingPractical advantages amenable to testing direct ecological relevance

Levels of organisation

growth reproductionetcetera

food

Clear boundaries mass/energy conservation

Levels of organisation

biotransformationelimination

uptake

etcetera

Clear boundaries mass/energy conservation

How to build models?

toxico-dynamicmodel

toxico-dynamicmodel

toxico-kineticmodel

toxico-kineticmodel

exposure pattern

effects over timereproduction growth

food

maintenance

development

storage

toxico-dynamicmodel

toxico-dynamicmodel

toxico-kineticmodel

toxico-kineticmodel

exposure pattern

effects over time

How to build models?

reproduction growth

food

maintenance

development

storage

Dynamic Energy Budget mass/energy conservation over entire life cycle

www.debtox.info

Standard DEB animal

food faecesassimilation

reservereserve

Standard DEB animal

structurestructure

food faeces

somatic maintenance

assimilation

1-

growth

reservereserve

mobilisation

Standard DEB animal

structurestructure

food faeces

maturity maintenancesomatic maintenance

assimilation

1-

growth reproduction

maturitymaturity bufferbuffer

maturation

reservereserve

mobilisation

eggs

p

Example

Dendrobaena octaedra and CuJager & Klok (2010)

Effect on assimilation

0 50 100 1501

2

3

4

5

6

7

8

9

time (days)

bod

y le

ngth

0 50 100 150

0

5

10

15

20

25

30

35

40

time (days)

cum

ulat

ive

off

sprin

g pe

r fe

mal

e

80 mg/kg120 mg/kg160 mg/kg200 mg/kg

Extrapolate ‘up’

Energy budget provides: – consistent life-history traits– as function of the environment

Simple link to existing population models

Extrapolate ‘up’

Euler-Lotka equation– in a constant environment, all populations grow exponentially …

Extrapolate ‘up’

Using the calibrated earthworm model …

0 50 100 1501

2

3

4

5

6

7

8

9

time (days)

body

leng

th

0 50 100 1500

5

10

15

20

25

30

35

40

time (days)

cum

ulat

ive

offs

prin

g pe

r fe

mal

e80 mg/kg120 mg/kg160 mg/kg200 mg/kg

Jager & Klok (2010)

Extrapolate ‘up’

Using the calibrated earthworm model …– predict growth in other constant environments

60 80 100 120 140 160 180 200

0

0.005

0.01

0.015

0.02

0.025

concentration (mg/kg soil)

pop

ulat

ion

grow

th r

ate

(d-1

)

food 100%

food 90%

Jager & Klok (2010)

Individual-based models

DEB-IBM, Martin et al. (2012)Every individual is a DEB individual

– stochasticity through mortality and feeding

Advantages– interaction with food, time-varying conditions– species differ mainly in parameter values …

DEB meets IBM

Calibrate model for Daphnia magna – performance at different constant food levels

Martin et al. (2013a)

DEB meets IBM

Martin et al. (2013a)

Good prediction of control dynamics– starvation and recovery model essential

Total Neonates

Juveniles Adults

DEB meets IBM

Using standard toxtest to predict population effects

Martin et al. (2013b)

Extrapolate ‘up’

Energy budget provides link to population models– Euler-Lotka and IBMs are suitable candidate

Can we continue this to ecosystem level? How to utilise ‘down’?

‘Adverse outcome pathway’

target siteinternaltoxicant

externaltoxicant

toxicokinetics

physiologicalprocesses

maintenance

assimilation

…

effects ontraits

energy budgetbiochemistry/-omics

Human toxicologyone specieslot’s of fundingfocus on individual health

Yang et al (2004)

‘Adverse outcome pathway’

internaltoxicant

physiologicalprocesses

maintenance

assimilation

…

externaltoxicant

toxicokinetics energy budget

In the meantime …knowledge to reduce animal testing–quantify model parameters in vitro–extrapolate between species/chemicals

To what extent can we simplify?

biochemistry/-omics

?

effects ontraitslife-cycle testing

Old paradigm

exposure assessment

risk

effects assessment

New paradigm

exposure assessment

risk

effects assessment

predicted‘impacts’ over

time

mechanisticfate model

mechanisticfate model

New paradigm

model parameters

mechanistic individual model(s)

mechanistic individual model(s)

population+ecosystem modelsenvironment

dedicated testing

Final words

We need mechanistic models for effects– to link fate models to environmental impacts– move away from descriptive statistics

Individual as central level of organisation– energy budget is an essential element– interaction between traits and with environment

Much more work is needed ….– collaboration across disciplines– focus on simplified mechanisms– focus on generality

Thanks for funding

IMS (204023/E40)

OAPPI (215589)

ENERGYBAR (225314/E40)

CREAM (PITN-GA-2009-238148)

More info

on DEB: www.bio.vu.nl/thb (2015 course, Marseille, FR)

on DEBtox: www.debtox.info (2016 summercourse, DK)

Caenorhabditis elegans

toxico-dynamicmodel

toxico-dynamicmodel

toxico-kineticmodel

toxico-kineticmodel

exposure pattern

growth/repro over time

Exposed to various chemicals– life-history traits– gene expression (transcriptional profiling)

Swain et al (2010), Wren et al (2011)

affectedprocessaffectedprocess

Caenorhabditis elegans

maintenance costs

maintenance costs

12 h after start repro

enrichment of genes associatedwith DNA integrity

and repair …

enrichment of genes associatedwith DNA integrity

and repair …

Swain et al (2010), Wren et al (2011)

biomarker over time

Calanus finmarchicus

Exposed to marine diesel– TKTD model for survival (‘GUTS’)– link biomarker response (GST)

toxico-dynamicmodel

toxico-dynamicmodel

toxico-kineticmodel

toxico-kineticmodel

exposure pattern

survival over time

Jager & Hansen (2013)

Calanus finmarchicus

toxico-dynamicmodel

toxico-dynamicmodel

toxico-kineticmodel

toxico-kineticmodel

exposure pattern

survival over time

Jager & Hansen (2013)biomarker over time