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

Chemical (and other) stress in DEB1: 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


Pyrethrin• pyrethrum (Chrysanthemum cinerariaefolium)• neurotoxic and repellent for insects


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: offense

“Venom” • spiders, snakes, cone snails, jellyfish ...

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 ...

In 1962 …

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

Reproduction test

Reproduction test

Reproduction test

Reproduction test

wait for 21 days …

Range of Concentrations

Dose-response plot

EC50

tota

l o

ffsp

rin

g

log concentration

NOEC

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

Organisms are complex

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

40

50

60

70

80

90

100

time (d)

bo

dy

len

gth

(µ

m)

0 2 4 6 8 10 1220

30

40

50

60

70

80

90

100

time (d)

bo

dy

len

gth

(µ

m)

H

M

L

0 2 4 6 8 10 120

20

40

60

80

100

120

140

160

time (d)

cum

ula

tive

nu

mb

er o

f eg

gs

0 2 4 6 8 10 120

20

40

60

80

100

120

140

160

time (d)

cum

ula

tive

nu

mb

er o

f eg

gs

H

M

L

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


(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


(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’

Corresponds with origin of DEB in 1979

egg


The 80’s … Kooijman (1981)

• toxicokinetics determines survival pattern

Kooijman & Metz (1984)• toxicants affect energy

budgets and thereby population response

egg


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”


Birth in 1996 … Windows software and

booklet (Kooijman & Bedaux, 1996)

Series of papers• Bedaux & Kooijman (1994)• Kooijman & Bedaux (1996)• Kooijman et al (1996)


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


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


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


Embryo division … Klok & De Roos (1996),

Klok et al (1997, 2007)• earthworm matrix model,

Bayesian approach


Applying ‘DEB3’ … Jager et al (2010)

• basis and mixtures

Jager & Klok (2010)• compare methods and

population level


New offspring … E.g., from current PhD

projects …

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

Final thought

Occam’s razor for dummies …

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

Documents

natural toxicants

death slide

eu slide

natural occurence

muchok performance slide

theoretical biology

forest fires slide

cigarette smoke natural