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State of play and outlookof modelling based prioritisation

Klaus Daginnus Institute for Health & Consumer Protection

Joint Research Centre, European Commission

Working Group E, Brussels 8-9 October 2009

http://ecb.jrc.ec.europa.eu/qsar/

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State of play

Hazard assessment •PBT & vPvB assessment

Use Assessment•Gathering data from REACH registration•Gathering data from SPIN www.spin2000.net/

Risk Ranking (level 1)•combined score from hazard & use assessment

4th expert group meeting•Methods to prioritise substances agreed•Timetable

5th expert group meeting•Presentation & discussion of the results

•DG ENV requested data from ECHA / SIEFs•No data available yet•Alternative gathering data From IUCLID implemented

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Starting list Inputs

Member States: • Monitoring data (all MS)• DK, SK, SV, UK

European ParliamentStakeholders: EEB, Greenpeace, IARWResearch

• NORMAN http://www.norman-network.net/index_php.php , • Joint Danube Survey 2 http://www.icpdr.org/jds/

OSPAR http://www.ospar.org/ (EEB, Greenpeace)• List of substances for priority action &• List of substances of possible concern

Joint Research Centre IHCP / Ex-ECB http://ecb.jrc.ec.europa.eu/

• PBT, RAR, IUCLID, ClassLab, ENDDA (in progress, see http://ec.europa.eu/environment/endocrine/strategy/short_en.htm )

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Starting list Output

CAS- Merge 2034 substances

Generation of 1892 Structures Input for QSAR

Generation of Substance identification data• SMILES, INCHI, IUPAC Names• REACH: Registration date, EC Number, ...• Existing Substances Regulation:

• PBT evaluation• Risk assessment reports: results aquatic concern• Classification & Labelling (substances hazardous for water R50-R53)

• Pesticides: Status EC 91/414

Source information: nominated by …

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Starting list modelling based prioritisation

WFD Starting list

19 25 25 31 34 127 148 152 158 266 308 318422 427

922

2034

0

500

1000

1500

2000

2500

SVEEB

IARW

OSPAR prior

ity EP

TCNES PBT

ESR

JDS se

dimen

t

JDS su

rface

wate

rUK

OSPAR poss

ible c

once

rn

ENDDA Cat

1&2

Norman

DK / R50-5

3

Monito

red S

ubsta

nces

CAS Mer

ge

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Hazard Assessment

REACH Guidance on Information requirements and chemical safety assessment

• Part B - Hazard Assessment & • Part C - PBT & vPvB assessment

or according to scientific progress

Hazard Scoring• Total Score (PBT) = Score P + Score B + Score T + Score ED

• If substance has been classified as P or B or T or is listed as endocrine active substance (CAT1&2), +1 has been added to the score

• Total Score (vPvB) = 4

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Hazard Assessment Persistence

Assessment P• PISUITE Version 4 http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm• Priority BIOHCWIN > BIOWIN• BIOHCWIN has been developed specifically for the biodegradation half life prediction of petroleum hydrocarbons• BIOWIN estimates the probability of rapid aerobic biodegradation of an organic compound in the presence of mixed population of environmental microorganisms

Assessment vP • OECD LRTP tool www.oecd.org/.../0,3343,en_2649_34373_40754961_1_1_1_1,00.html • The OECD Pov and LRTP Screening Tool has been developed with the aim of using multimedia models for estimating overall persistence (Pov) and long-range transport potential (LRTP) of organic chemicals at a screening level, in the context of PBTs/POPs assessments.

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Assessment B• Priority: experimental data > QSAR• Experimental data from PhysProp http://www.srcinc.com/what-we-do/product.aspx?id=133, data are accessible also from EPISUITE• Applied QSAR models:• EPISUITE (BCFBAF update Jan 2009)• CAESAR http://www.caesar-project.eu/ • JRC BCF model• Application of worst case for experimental data / QSAR at the 1st level

Hazard Scoring Bioaccumulation

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Hazard Scoring Toxicity

• Priority experimental data > QSAR• Priority chronic > acute toxicity data • Experimental data

• ECETOC (TR 0091) http://www.ecetoc.org/ • Footprint www.eu-footprint.org  • DSSTOX www.epa.gov/ncct/dsstox/

• QSAR data• 4 QSAR models [ADMET Predictor proprietary model, 3 JRC models) using the DSSTOX data were run to estimate toxicity using a consensus approach

• PNECs were calculated with preference to• experimental data > QSAR (AF 1000) • chronic > acute toxicity data

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Workflow Hazard Scoring Toxicity (ECETOC)

1. Data mining ECETOC

2. Merging & Classification

MergeECETOC

436

MergeECETOC

WFD203

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Exposure Scoring

Use assessment

Use index0.1 controlled system0.2 industrial use0.5 wide dispersive use1.0 used in the environment (pesticides, biocides)

Use index * Production volume (t/y)

Score0 = 0-1 1 = 1-102 = 10-1003 = 100-10004 > 1000

IUCLID • 921 substances (merge WFD list)• > 12000 dossiers

SPIN• 301 substances

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Exposure assessment score

Hazard assessment score

4 3 2 1 0

4 1 1 2 3 53 1 2 2 3 52 2 2 3 4 51 3 3 4 4 50 5 5 5 5 0

Risk Ranking Scoring

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Data pass, Data fail

P B T

P & B & TList

ScoreRisk

Workflow Risk Ranking (PBT)

Excel Table + data for PEC

calculationScoreRisk

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Proposed application to estimate PEC/PNEC ratio for substances with risk score = 1

ECETOC has developed a tiered approach for calculating the exposure and related risks to consumers, workers and the environment caused by chemicals :

Tier 1: based on pre-defined and conservative use scenarios corresponding to Environmental Release Categories (ERC) described under REACH Guidance (Chapter R.16)

Tier 2: detailed risk assessment on previously identified uses (additional more realistic exposure input)

Developed in Excel, contains the user interface and the datasheets

Freely downloadable after registration from: http://www.ecetoc.org/tra

ECETOC TRA tool

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ECETOC TRA tool

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Summary

• Starting list of chemicals completed• relevant databases for Toxicity and Production volumes & uses data-mined• State of the art QSARs applied to fill data gaps

• not applicable for inorganic, metall-organic compounds• Risk ranking carried out timely for Starting list, excel table available

• Scores (hazard, use assessment, risk ranking)• PNECs water calculated• Substance identification data (Names, source of nomination, CAS, SMILES, ...)• Physical chemical data (log Kow, Solubility, multi-media fate, as input for PEC calculation)• De-listing criteria (legal status 91/414, ...)

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Outlook

• Calculation of PEC and PEC/PNEC by TRA tool ECETOC • Refinement of PEC & PNEC by peer review recommended

• risk assessment reports available?• data from research available? E.g. KNAPPE www.knappe-eu.org/ , NORMAN, …

• JRC report in progress