BANGKOK dec 2008 ECOTOXICOLOGY III FINAL + QUESTIONS

Bangkok Ecotoxicology III p.1ECOTOXICOLOGY: Toxicity testing for environmental effects and their endpoints Ecological risk assessment: exposure and effects effects at ecosystem level

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Bangkok Ecotoxicology III p.1

ECOTOXICOLOGY:

Toxicity testing for environmental effects

and their endpoints

Ecological risk assessment: exposure and effects

effects at ecosystem level objective of ecological risk assessment: supply information to

protect our environment for adverse effects of chemicals

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Test systems used in ecological risk assessment

single species tests: acute effects (mortality)

single species tests: semi-chronic, sublethal effects

single species test with effect at population dynamics

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Semi-chronic tests with algae, Daphnia and fish

effects: survival, growth, reproduction, outcome of eggs,

development, behaviour

test systems: static, daily renewal or flow through

Example: early life stage test with fish (ELS test)

Question

What endpoints do you consider most relevant for

ecotoxicological risk assessment?

What endpoints would you suggest for top predators in

ecosystems?

What is a significant difference between human and

ecotoxicological risk assessment?

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Test systems

system:

in vivo (whole organisms)

or in vitro (cells, protein)

dosing systems:

static

daily renewal

flow through system (continuous renewal)

Test system: concentration of chemicals

problems:

decrease of concentration during test

making “good” test solutions for:

low soluble or

low boiling test chemicals

from van Leeuwen and Hermens, 1995: Risk Assessment of Chemicals

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presence of suspended particles

Influence of exposure time on effect concentration

Reaching steady state will depend on:

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Influence of pH on effect concentration

Bioavailability of heavy metals in soil

Chapter 6 (van Leeuwen)

Influence of hardness on LC50 in rainbow trout

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Speciation of aluminium as a function of pH

1.0 0.8 0.6 0.4 0.2 0.0

4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 3.5

AlSO+AlOH 2+

Water pH

Influence of organic carbon content on bioavailability

30 25 20 15 10 5 0 1.0 1.5 2.0 0.5

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- Organisms have different sensitivities to a chemical substance

- Variation in sensitivity strongly depends on mode of action

data from Verhaar, 1991 and Legierse, 1997

1,3,5-trimethylbenzene versus chlorothion

oxidation (NADPH)

de-alkylation GSH

OP=SOCH3OCH3

NO2Cl

O P=SOH OCH3

NO2Cl

O P=OOCH3OCH3

NO2Cl

specific mode of action:

non specific mode of

action in acute tests

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Reasons for differences in sensitivity

Environmental factors (external)

pH, hardness, salinity, suspended particles

experimental artifacts ?

Internal factors

uptake / accumulation kinetics

biotransformation capacity (in case of bio-activation)

presence of target (example: neurotoxicants, herbicides)

sensitivity of the target or receptor

Setting safe concentrations at the ecosystem level

Impossible to test many different species

number of different protozoa: 30.000

number of different crustaceans: 25.000

In practice: data for 3-6 test organisms

How to set safe concentrations:

- use of application factors

- use of extrapolation techniques

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Kooijman, van Straalen,

Wagner and Lokke, Aldenberg and Slob

0.50 0.40 0.30 0.20 0.10 0

Extrapolation technique: logistic distribution to calculate

HC5

HC5:

hazerdous concentration

for 5 % of the species

chosen as safe concentration

at ecosystem level

input:

NOECs for at least 5 species

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Extrapolation techniques

Strengths and weaknesses:

- Assumption of certain distribution

which is not valid for several

chemicals (example: specific mode

of action)

- Certain organisms are key species

- Takes into account that differences

in sensitivity depend on the chemical

(mode of action)

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Activity of a chemical depends on:

Cl

Cl Cl

Cl

OH

tetrachlorobiphenyl

methanolhydrophobicity / solubility in water

size

electronic parameters: charge

Quantitative structure-activity relationship: properties

Hydrophobic parameters

Aqueous solubility

Octanol-water partition coefficient (Kow )

Total Surface Area (TSA)

Total Molecular Volume (TMV)

Hammett sigma substituent constants (s)

Reduction potential (E1/2)

Steric parameters

Total Surface Area (TSA)

Total Molecular Volume (TMV)

Taft substituent constant (Es)

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Question

Which chemical or environmental properties do you consider to

be most important for environmental occurrence of the following compounds?

1 Chlorinated biphenyls (PCBs)

2 Organophospate esters (e.g parathion)

3 Pyrethroids (e.g permethrin)

4 Mercury

Prediction of fate and effects via quantitative

structure-activity relationships (QSARs)

biodegradation rates no-effect concentrations soil sorption

bioaccumulation

quantitative model relating Y to X (QSAR)

Y = f (X)

prediction of fate or effect properties

from chemical structure for related chemicals

Cl

O

O Cl

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QSAR for ecotoxicity

bioconcentration / partitioning

effect concentrations

endocrine disruption

Bioconcentration

uptake via food or particles

uptake via gills (aqueous phase)

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Bangkok Ecotoxicology III p.31 2

models are developed for relatively simple chemicals:

• no biotransformation

• uptake only via aqueous phase

Relation between bioconcentration factors and

octanol-water partition coefficeints (Kow)

Question

Can explain what other possible reasons there could be

(besides biotransformation) that causes deviation from the

observed QSAR ?

Think of at least two groups of compounds that might deviate from this QSAR due to the effect of biotransformation

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Prediction of ecotoxicityFour classes in acute toxicity

class 1: chemicals with base-line toxicity (non-polar narcosis)

class 2: chemicals that act by polar narcosis

class 3: alkylating agents (reactive towards nucleophiles: SH,

OH, NH) leading to cytotoxicity, membrane irritation,

mutagenicity or carcinogenicity

class 4: chemicals with specific modes of action

Verhaar, 1992 / Veith, 1990 / Bradbury, 1990 / Hermens, 1989

alcohols, ethers, (chorinated) aromatic hydrocarbons

data from Könemann, 1981

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Class 1: chemicals that act by narcosis

NOEC early life stage test (reproduction, growth)

data from Call, 1985 / van Leeuwen, 1990

blocking of protein channel: disturbance of transport of nerve impulses

narcosis

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CH3

N+OO

CH 3

N+OO

Cl

NH 2

anilines, phenols and nitroaromatics

data from Könemann, 1981 / Hermens, 1984 / Deneer, 1987

Reactive chemicals

Examples: epoxides, aldehydes, unsaturated chorinated hydrocarbons

These chemicals may react with nucleophiles (NH, OH and SH)

in for example DNA, proteins, glutathion, leading to:

irritation

cytoxiciity

DNA damage (carcinogens, mutagens)

more toxic than narcosis

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O O

Br I

O

epoxides, unsaturated chlorohydrocarbons, aldehydes, etc.

data from Hermens, 1985 / Deneer, 1988

Class 4: chemicals with a specific mode of action

pentachlorophemol organophosphates

Cl

Cl Cl Cl Cl Cl

CCl3

Cl Cl

OH Cl

Cl Cl Cl

P=S OCH3OCH3

data from Hermens, 1982 / De Bruijn, 1992

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Chemical domain of models: example

Acute toxicity to fish:

(mol/L)

Application of QSARs

predictions of effect concentration for risk assessment

classifying chemicals into “mode of action” classes (100.000 chemicals on EINECS)

mechanistic studies (receptor mediated effects)

priority setting

evaluation of effects of mixtures

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