MODELKEY ( 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 ( GOCE) is a research project funded by AA-EQS Log TU Max Daphnia magna SPEAR [%] n = 30 Von der Ohe et al 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 ( GOCE) is a research project funded by Motivation: Evidence of Toxic Stress AA-EQS Log TU Max Daphnia magna SPEAR [%] 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/L LC µg/L EQS 0.03 µg/L LC µg/L

MODELKEY ( GOCE) is a research project funded by 50 mio known chemicals 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 ( 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 ( 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 ( GOCE) is a research project funded by Monitoring Data Evaluation Compoundn% sites Bis-(2-ethylhexyl)-phthalat Chlorfenvinfos 9100 Dichlorvos Mevinfos Parathion-ethyl PCB Azoxystrobin ,4'-DDT Chlorpyrifos62 95 PCB Diazinon13 92 Tricyclohexyltin22 91 Nonylphenol-1-ethoxylate10 90 Example: Compounds with log TU > -3 (Daphnia magna) in Elbe Priority pollutants

MODELKEY ( 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) Ibuprofen Indomethacine Propranolol Temperature A1A A2A A3A LL1A LL2A LL3A LL4A A1B A2B A3B LL1B LL2B LL3B LL4B A1C A2C A3C LL1C LL2C LL3C LL4C Muñoz et al., 2009, ET&C 28: Monitoring: Correlation approach Tubificidae Chironomus Good correlation between the abundance and biomass of several benthic invertebrates (Tubifex, Chironomus) and pharmaceuticals (ibuprofen, propanolol, indomethacine)  Causal pathway assessment, large scale monitoring

MODELKEY ( 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

MODELKEY ( 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 ( GOCE) is a research project funded by Effect Directed Analysis thyroid hormone disturbing potency estrogenicity tumor promotion (inhibition of GJIC) number of positive wells TA98 TA98 with metabolic activation mutagenicity PCBs, PCDD/Fs, halogenated pesticides PAHs polar compounds Polar compounds play a key role for many hazards due to con- taminated sediments! Even more if bioavailability is considered

MODELKEY ( GOCE) is a research project funded by Effect Directed Analysis Non-regulated compounds identified by EDA studies (algal toxicity, endocrine disuption, mutagenicity) Examples from sediments benzanthrone 2-methylanthra- quinone triclosan N-phenyl-2- naphthylamine dinitropyrenes nandrolone tonalide traseolide galoxolide tris(2-chloroisopropyl) phosphate

MODELKEY ( 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 ( 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 ( GOCE) is a research project funded by Thanks a lot for your attention