modelkey (511237-goce) is a research project funded by suggestions for the derivation of candidate...
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MODELKEY (511237-GOCE) is a research project funded by
Suggestions for the derivation of candidate compounds for monitoring and prioritisation
Werner Brack, Jan Balaam, Nicole Bandow, Damia Barcelo, Rikke Brix, Edwin Foekema, Stefania Gottardo, Marja Lamoree, Pim
Leonards, Urte Lübcke-von Varel, Miroslav Machala, Isabel Munoz
Gracia, Claudia Schmitt, Mechthild Schmitt-Jansen, Katrin Schwab,
Peter von der Ohe, Kevin Thomas, Jana Weiss, Dick de Zwart
MODELKEY (511237-GOCE) is a research project funded by
AA-EQS
Log TU Max Daphnia magna-4 -3 -2 -1 0
0
20
40
60
80
SP
EA
R [
%]
n = 30
Von der Ohe et al. 2009. IEAM 5
AF 1000 LC50
Motivation: Evidence of Toxic Stress
In all investigated river basins: Disappearance of sensitive species (SPEAR) with increasing contamination
Significant effects on invertebrate community at concentrations factor 1000 below acute LC 50 to Daphnia.
In agreement with AF 1000!
MODELKEY (511237-GOCE) is a research project funded by
Motivation: Evidence of Toxic Stress
AA-EQS
Log TU Max Daphnia magna-4 -3 -2 -1 0
0
20
40
60
80
SP
EA
R [
%]
Chlorfenvinphos
Chlorpyrifos
Mesocosm-based EQS
However: be careful with EQS based on chronic or mesocosm data!
These data do not reflect species interactions and long term effects.
Values with AF<1000 relative to acute toxicity are not protective.
EQS 0.1 µg/LLC50 0.3 µg/L
EQS 0.03 µg/LLC50 1.25 µg/L
MODELKEY (511237-GOCE) is a research project funded by
http://www.modelkey.org
50 mio known chemicals
5.00 10.00 15.00 20.00 25.00 30.00 35.000
500000
1000000
1500000
2000000
2500000
3000000
3500000
4000000
4500000
5000000
5500000
6000000
6500000
7000000
7500000
8000000
8500000
9000000
9500000
1e+07
Time-->
Abundance
TIC: WER046.D
thousands of compounds in real world samples
33 priority pollutants (WFD)
Motivation: The dilemma of complexity
How to define candidate compounds for monitoring and prioritisation?
MODELKEY (511237-GOCE) is a research project funded by
Current Prioritisation Approach
1) Monitoring-based approach:
• Monitoring data from > 4 countries
• Prioritisation based on (P)EC/PNEC (arithmetic means)
• (P)EC>PNEC at > 10% of sites prioritisation
2) Modeling-based approach • Larger list of candidate compounds (different sources)
• Exposure assessment based on total production and use
• Hazard assessment based on experimental or QSAR data related to PBT and endocrine disruptor properties
• Risk score equal to 1 prioritisation, PEC/PNEC ranking
MODELKEY (511237-GOCE) is a research project funded by
MODELKEY suggestion: Add field relevance-based approach
Monitoring data evaluation
(basin scale)
Prediction of Toxic Units
(TU) or Potentially Affected Fractions (PAF) of
communities
Correlation between species similarity
matrix and environmental
matrix
Effect-directed analysis in water, sediments and biota to identify
toxicologically relevant compounds
Site-specific investigations at
sources and sinks
Exposure modeling,
trophic magnification
Monitoring programs
MODELKEY (511237-GOCE) is a research project funded by
Monitoring Data Evaluation
PO O
OH
O
CH3
Cl
Cl
PS
O
O
O
CH3
CH3N
+O
-
O
Compound n % sitesBis-(2-ethylhexyl)-phthalat 786 100
Chlorfenvinfos 9 100
Dichlorvos 11 100
Mevinfos 47 100
Parathion-ethyl 25 100PCB 77 25 100Azoxystrobin 187 99
2,4'-DDT 444 97
Chlorpyrifos 62 95
PCB 126 16 94
Diazinon 13 92
Tricyclohexyltin 22 91
Nonylphenol-1-ethoxylate 10 90
Example: Compounds with log TU > -3 (Daphnia magna) in Elbe
Priority pollutants P
O
OO
O
CH3
CH3
CH3
O
OCH3
MODELKEY (511237-GOCE) is a research project funded by
Physical and chemical parameters (pH, water temperature, conductivity, oxygen concentration, nutrients) and 29 pharmaceuticals versus biological communities (diatom and invertebrate communities)
Multivariate statistical analysis: (RDA: redundancy analysis)
-0.4 1.2
-0.6
1.0
Ibuprofen
Indomethacine
Propranolol
Temperature
A1A
A2A
A3A
LL1A
LL2A
LL3A LL4A
A1B
A2B
A3B
LL1B
LL2B
LL3B
LL4B
A1C
A2CA3C
LL1C
LL2C
LL3C
LL4C
-0.4 1.0
-0.6
0.8
TubificidaeEnchytraeidae Naididae
Other Ephemeroptera
Baetis
Caenis
Chironomus spp
Cricotopus sp
Cryptochironomus
Nanocladius
Orthocladiinae
Polypedilum Rheocricotopus
Stictochironomus
Tanytarsus
Tanypodinae
Muñ
oz e
t al
., 2
009,
ET
&C
28:
2706
-271
4
Monitoring: Correlation approach
Tubificidae
ChironomusGood correlation between the abundance and biomass of
several benthic invertebrates (Tubifex, Chironomus) and
pharmaceuticals (ibuprofen, propanolol, in
domethacine)
Causal pathway assessment, large scale monitoring
MODELKEY (511237-GOCE) is a research project funded by
Site-specific: Effect Directed Analysis
• Site specific
• Endpoint specific
• Based on selected in vivo or in vitro biotests
• No a priori knowledge on or selection of compounds required
• Applicable to any matrix (water, sediments, biota, …)
• Site selection: integrative sink area or source area
environmentalcontamination
biologicalanalysis
biologicalanalysis
chemicalanalysis
fractionation
confirmation
toxicant
MODELKEY (511237-GOCE) is a research project funded by
Effect Directed Analysis
Example: Sublethal effects by sediment contamination
Conventional sediment assessment: Focus on non-polar priority pollutants PAHs, chlorinated pesticides (DDT, HCH, HCB, aldrin, dieldrin…) and PCBs and PCDD/Fs
MODELKEY (511237-GOCE) is a research project funded by
Effect Directed Analysis
0
20
40
60
80
100
120
P1
P2
P3
P4
P5
P6
P7
P8
P9
P10
P11
P12
P13
P14
P15
P16
P17
P18
fractions
% o
f co
ntro
l
0
500
1000
1500
2000
2500
3000
3500
4000
P1
P2
P3
P4
P5
P6
P7
P8
P9
P1
0
P1
1
P1
2
P1
3
P1
4
P1
5
P1
6
P1
7
P1
8
pm
ol T
4 eq
/g d
ry s
edim
ent
0
5
10
15
20
25
30
35
40
P 1
P 2
P 3
P 4
P 5
P 6
P 7
P 8
P 9
P 1
0
P 1
1
P 1
2
P 1
3
P 1
4
P 1
5
P 1
6
P 1
7
P 1
8
% m
ax
imu
m i
nd
uc
tio
n
thyroid hormone disturbing potency
estrogenicity
tumor promotion (inhibition of GJIC)
0
10
20
30
40
50
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
nu
mb
er
of
po
sit
ive
we
lls
TA98
TA98 with metabolicactivation
mutagenicity
PCBs, PCDD/Fs, halogenated pesticides PAHs polar compounds
Polar compounds play a key ro
le for m
any hazards due to con-
taminated sediments! Even more if b
ioavailability is considered
MODELKEY (511237-GOCE) is a research project funded by
Effect Directed Analysis
Non-regulated compounds identified by EDA studies (algal toxicity, endocrine disuption, mutagenicity)
Examples from sedimentsO
benzanthrone
O
O
CH3
2-methylanthra-quinone
O
OH
Cl
Cl
Cltriclosan
NH
N-phenyl-2-naphthylamine
N+ O
-O
N+
O-
O
dinitropyrenes
O
Onandrolone
O
tonalide
O
traseolide
O
galoxolideCl
OP
O
OCl
O
Cl
tris(2-chloroisopropyl) phosphate
MODELKEY (511237-GOCE) is a research project funded by
Conclusions
• Strong evidence on toxic stress indicators available
• Priority pollutants are poor predictors for adverse effects
• Mesocosm/chronic tox-based EQS with AF<1000 are not protective
• Powerful tools for deriving candidate compounds from monitoring data available (TU, msPAF, correlation)
• Include field-based evidences by EDA at selected sites in candidate compound identification
• New evidences on the importance of polar emerging pollutants for toxic stress
• Define and monitor priority effects together with priority pollutants
MODELKEY (511237-GOCE) is a research project funded by
We still see only the tip of the iceberg!
Conclusions
Research needs: Analytical tools, databases and computer tools for
structure elucidation of difficult (polar, thermolabile, multifunctional….) unkowns.
Reliable tools for prediction of chromatographic retention, spectroscopic properties and effects
Combine EDA with strong biological diagnostic tools (omics)
Integrated approaches for compound prioritisation
MODELKEY (511237-GOCE) is a research project funded by
Thanks a lot for your attention
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