1. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 The Testing Methods Process: From Current Legislation to REACH Juan Riego Sintes Steven Eisenreich Croatia – JRC-ECB InfoDays 11-13 December 2006 Zagreb, Croatia

2. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Objectives of this talk Give general information on: General on TMs - Why do we need standardized Testing Methods? - Which methods do we have, where are them? - How and by whom are they developed? Extract on Regulatory Acceptance Activities in the Interim period Testing Methods in REACH / RIP 3.3

3. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 1 Protecting People and the Environment from Dangerous Chemicals RISK ASSESSMENT DETERMINATION OF HAZARDOUS PROPERTIES OF CHEMICALS DETERMINATION OF HAZARDOUS PROPERTIES OF CHEMICALS RISK MANAGEMENT FOR HUMANS AND THE ENVIRONMENT RISK MANAGEMENT FOR HUMANS AND THE ENVIRONMENT HAZARD IDENTIFICATION AND ASSESSMENT HAZARD IDENTIFICATION AND ASSESSMENT CLASSIFICATION AND LABELING TESTING METHODS Why

4. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Single Market and Free Trade FREE MOVEMENT OF GOODS MUTUAL ACCEPTANCE OF DATA HARMONISATION OF TESTING METHODS for HAZARDOUS OR DANGEROUS CHEMICALS HARMONISATION OF TESTING METHODS for HAZARDOUS OR DANGEROUS CHEMICALS based on relies on Both at EU and global level e.g. OECD Both at EU and global level e.g. OECD Why MAD agreement

5. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Testing Methods Annex V structure Current: ANNEX V Dir. 67/548/EEC* Current: ANNEX V Dir. 67/548/EEC* Contains standardised Testing Methods to determine the properties of chemicals Part A. Methods for the determination of PHYSICO-CHEMICAL PROPERTIES Part A. Methods for the determination of PHYSICO-CHEMICAL PROPERTIES Part C. Methods for the determination of ECOTOXICITY Part C. Methods for the determination of ECOTOXICITY Part B. Methods for the determination of TOXICITY Part B. Methods for the determination of TOXICITY 88/302/EEC 92/69/EEC 93/21/EEC 96/54/EC 98/73/EC 2000/32/EC 2000/33/EC 2001/59/EC 2004/73/EC 88/302/EEC 92/69/EEC 93/21/EEC 96/54/EC 98/73/EC 2000/32/EC 2000/33/EC 2001/59/EC 2004/73/EC Where Future: Testing Methods regulation * These methods are legally binding

6. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Where

7. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 EUROPEAN CHEMICALS BUREAU WA 1 Classification and labelling WA 2 New Substances WA 3 Testing Methods WA 4 Existing Substances WA 5 Import/ Export WA 6 Biocides Carries out and co-ordinates scientific/technical work needed for the implementation of EU legislation in the area of chemicals control Current 67/548/EEC Draft REACH proposal Overlapping regulations and actions Who

8. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 CO-ORDINATE the DEVELOPMENT INTRODUCTION of ADAPTATION TO TECHNICAL PROGRESS (ATP) DEVELOPMENT INTRODUCTION of ADAPTATION TO TECHNICAL PROGRESS (ATP) TESTING METHODS (Annex V to Dir. 67/548/EEC TESTING METHODS (Annex V to Dir. 67/548/EEC Duties of Testing Methods Work Area Who

9. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Testing Methods Tasks - Co-ordinate COM and EU needs and input into OECD Test Guidelines Programme (National Co-ordinators Meeting). - Promote Testing Methods development for EU legislation (co-ordinated with OECD as far as possible). - Organise transfer of OECD accepted Test Guidelines into Annex V. - Co-operate with the European Centre for validation of Alternative Methods (ECVAM) to promote development and to accompany adoption of alternative Testing Methods within EU legislation and OECD TG programme. - Participate in relevant UN activities for global harmonisation. - Organise, support and evaluate ring tests or validation studies. - Organise and host expert meetings. - Develop review documents. Who and how

10. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Testing Methods Development (II) Member States Competent Authorities Scientific Community National Co-ordinators Meeting or written procedure advice on work plan priorities preferred approach European Chemicals Bureau OECD TG Programme National Co-ordinator Development by ECBDevelopment by MS Working Groups Task Forces Experts’ Meetings Workshops NC’s Meeting or written procedure Decide to introduce in Annex V TM C&L New Substances Existing Substances Biocides Other Commission Services Commission Services Consultants Experts Who and how

11. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Preparation of proposal for ATP Interservice Consultations Proposal to Member States ATP Committee Publication in OJ Draft Method Meeting of NC’s or written procedure Approval to introduce into Annex V Formatting Commenting Round(s) Final version of Testing Method Meeting(s) of NC’s or Experts Meeting or written procedure Approval by NC’s Translation in all official languages Checking by NCsCorrection of translated versions Final translated versions of TM DG ENV Introduce Corrections and/or Guidance Testing Methods Development (III) Draft Testing Method in Annex V format Who and how

12. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 REGULATORY ACCEPTANCE of TMs (extract)

13. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 ROLES IN THE EU (current)* (regarding to TMs acceptance) EUROPEAN COMMISSION: Coordinates and prepares proposals Has legislative initiative Review, endorse, implement MEMBER STATES: Give opinion and advice Vote Commission’s proposal Review, endorse, implement, enforce DG Environment: “Chef de file” Policy responsible Competent Authorities: Policy responsible ECB: Technical matters and delegated duties National Coordinators: Technical matters and delegated duties *In future similar for TMs, where Agency?

14. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Ensure acceptance of data at OECD level (among authorities, 30+3) Harmonized guidelines at OECD level MAD* agreement: If you use these, I will accept Ensure acceptance at EU level (within and among authorities, 25+2+1) Harmonized methods at EU level Legally binding: You must use these EU Annex VOECD TG *MAD: Mutual Acceptance of data HARMONISATION Aims to allow Single market, free trade, free movement of goods at EU and global level Important to keep harmonization between both sets

15. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 INTERIM from Annex V to the new Testing Methods Regulation and REACH

16. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Testing Methods (Interim) Objective: Coordinate the development, introduction and adaptation to technical progress of Testing Methods of Annex V to Dir 67/548 and contribute to relevant REACH Implementation Projects (RIP). Maintain functioning current system and prepare for new (at COM, EU and OECD levels): Methods needed for the base set. Alternative or in vitro methods. Methods for EU specific needs. Contribute to RIP projects, in particular developing new “Intelligent” Testing Strategies (ITS) (e.g. RIP 3.3 ) Identify and prioritize new or updated methods needed for REACH implementation. Cooperate with the leading DG(s) in order to finalise the new Regulation on Testing Methods Collaboration with EU MS National Coordinators and other stakeholders. Collaboration with OECD Collaboration with ECVAM and other COM Units How: Current priorities:

17. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 REACH and Test Methods General political objectives of REACH RIPs RP 3.3 motivation Information integration: ITS Testing requirements Adaptations and waiving Overview of RIP 3.3 Objectives Deliverables Management Status

18. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 (some) REACH Political objectives How are they reflected in the Testing Strategies? Protection of human health and the environment Maintenance and enhancement of the competitiveness Prevent fragmentation of internal market Increased transparency Integration with international efforts Promotion of non-animal testing (= avoid testing in animals) Conformity with EU obligations under WTO

19. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Protecting health and environment –Gathering and generating the information required to prepare a Chemical Safety Report and eventually manage the risks. –Priority evaluation of substances of particular concern (CMR, PBT, vPvB,…) or when an aggregate tonnage trigger has been reached. This may involve generating new data REACH objectives (II)

20. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Maintaining and enhancing competitiveness –Exhaustive use of existing information (existing test results, human evidence, in vitro,…) –Use of non-test based information (QSAR, grouping,…) –No testing for very low production volumes (below 1 T) (and limited between 1-10 T) –No requirements for polymers and intermediates (with limited exposure potential) –Exposure driven tailored testing (exposure scenarios) –R&D exemption (up to 10 y) –Sharing of data REACH objectives (III)

21. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Promoting non-animal testing Same as previous and, in addition: –Allow non (not yet)-validated in vitro methods in some circumstances –Evaluation of proposals for substance-tailored testing involving animals (in particular required under annexes IX and X) –Limited testing in animals below 10 Tonnes REACH objectives (III)

22. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 REACH Implementation Projects (RIPs) RIP 1: REACH Process Description; RIP 2: REACH – IT; RIP 3: Technical Guidance and Tools for Industry; RIP 4: Technical Guidance and Tools for Authorities; RIP 5: Setting up the Pre-Agency RIP 6: Setting up the Agency RIP 7: Commission preparations for REACH Preparing for REACH: RIPs

23. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Guidance for Industry on how to fulfil Information Requirements (RIP 3.3) Information Integration before Testing Endpoint information (Q)SARs Read Across In-vitro Exposure Scenarios (Annex IX/X) Existing information TESTING ? RIP 3.3 Intelligently Integrating Information The 3 I’s

24. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Testing Annexes (Info requirements) Annex VI: Guidance on testing annexes plus basic information requirements Annex VII: Information requirements for >1T Annex VIII: Additional Information requirements for >10T Annex IX: Additional Information requirements for >100T Annex X: Additional Information requirements for >1000T Annex XI: General Guidance and rules for Adaptation of the standard test regime Testing Methods Regulation But always hand in hand with Annex I (CSR)!! RIP 3.3 background (I)

25. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 1Gather + share existing information on – Properties: test results, QSAR estimates, human data,… – Uses: current and foreseen – Exposure – Risk Management Measures: implemented or proposed 2Identify precise information needs on the basis of – Tonnage – Use – Exposure – Risk Management Measures General guidance in Annexes VI and XI of draft REACH (1) RIP 3.3 background (II)

26. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 General guidance in Annexes IV and IX of draft REACH (2) 3Identify information gaps and consider how missing information can be generated Consider (Annex IX): –Testing not scientifically necessary Quality GLP and Annex X quality data exists Adequate non-GLP or non-Annex X data exists human data weight of evidence QSAR grouping or read across in vitro data –Testing is technically not possible –Substance-tailored exposure-driven testing (consider exposure scenarios) 4Generate new information or propose testing strategy According to Annexes VII to X and using the Testing Methods of the New Regulation RIP 3.3 background (III)

27. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Development of Guidance for Industry on how to fulfil Information requirements (RIP 3.3) Overview Introduction (Objectives, Deliverables, Organisation) Tasks (specific deliverables, status) RIP 3.3

28. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Objectives of RIP 3.3 Guidance for industry on how to fulfill the information requirements on intrinsic properties (Annex VI to XI) and how to use all information and testing in an optimal way for decision-making under REACH This should allow for: Carrying out Chemical Safety Assessment (CSA) –includes whether substance is PBT or vPvB Classification and labelling (C&L) –includes assessment whether a substances is CMR

29. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 RIP 3.3 Deliverables Guidance on strategies for generation of information on relevant inherent properties; should explain and illustrate: How to find and use existing information (including human data, non GLP studies and other information obtained with non-standard test methods); How to implement the rules for adaptation as provided in the different annexes, especially for substances manufactured/imported in higher tonnages; The guidance shall provide the rationale for adaptation (waiving) from the test requirements specified in column 2 of Annexes VIII-X.

30. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 RIP 3.3 Partners and Organisation (I) RIP 3.3. Consortium: –CEFIC (lead) –Concawe –ECETOC –Environment Agency (UK) –DK EPA –Eurométaux –INERIS (F) –KEMI (S) –OECD –RIVM (NL) –TNO (NL) All are members of Project Management Group (PMG) plus DG ENTR and DG JRC ECVAM/ECB –Ad hoc working groups –Endpoint Working Groups (EWG)

31. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 RIP 3.3 Tasks Task 1 : General structure / cross-cutting issues Task 2 : Specific Endpoint Guidance Task 3 : Chemical Categories / Read Across guidance Task 4 : Preparation of draft TGD

32. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Task 1: General structure / cross-cutting issues

33. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Task 1 ToRs,Templates (HH and Env) and source documents for EWGs Harmonisation of horizontal issues and 1General introduction to REACH 2General Decision Making Framework 2.1Introduction 2.2General Decision Making Framework 3.Information requirements 3.1Information sources/searching 3.2REACH Annexes VI-X interpretation 4 Evaluation of available data 4.1Adequacy 4.2Reliability 4.3Relevance 4.4Fit for purpose 5Considerations affecting information requirements and testing strategies 5.1Use of existing data 5.2WoE 5.3QSAR 5.4In vitro 5.5Grouping & Read across 5.6Testing is technically not possible 5.7Substance tailored exposure driven testing 5.8Toxicokinetics 5.9Non standard Substances 8Conclusions on Hazard assessment 8.1Concluding C&L 8.2Concluding DNEL 8.3Info not adequate either for C&L and/or DNEL 8.4Remaining uncertainties 9 GlossarySTATUS: 2 nd draft available in December

34. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 6Dose response relationship 6.1 Derivation of NOAEL, starting point, assessment factors 6.2Modification of NOAEL or LOAEL 6.3Different routes of exposure and bioavailability 6.4Deriving adequate starting point 7ITS 7.1Phys-chem &adsoption desorption 7.2Skin&Eye Irritation/corrosion & respiratory irritation 7.3Skin & respiratory sensitisation 7.4Acute toxicity 7.5Repeated dose 7.6Reproductive & Developm. Toxicity 7.7Muta and Carcinogenicity 7.8Aquatic Toxicity; long term tox to sediment 7.9Degradation/Biodegradation 7.10 Bioconcentration & Bioaccumulation/ long term birds 7.11 Effects on Terrestrial Organisms RIP 3.2 Task 2

35. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Task 2: Development of Guidance & ITS for Specific Endpoints (general) PURPOSE OF REACH Balance between ensuring high level of Human Health and Environmental protection - limitation of EU industry administrative burdens/costs in order to maintain competitiveness and innovative capacity (Council document 7524/06 AD1) MEANS Providing adequate information for C&L and for carrying out CSA HOW - Providing integrated testing strategies. - Minimizing animal testing THEREFORE - Integrated testing strategy: move from old to new strategy; tiered approach - Guidance which is accessible and understandable for non-expert - Scientifically robust but practical

36. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Task 2: Development of Guidance & ITS for Specific Endpoints DELIVERABLES: Guidance on identifying information sources and how to ensure the reliability of the used information (generic aspects part of Task 1); A testing strategy to help registrants provide adequate and relevant information for registration sufficient for –Carry out Chemical Safety Assessment (CSA) –Classification and labelling Guidance on when and how to use alternative information (instead of (animal) testing) including guidance on what is “adequate and reliable documentation”; HOW: by specific Endpoint Working Groups (EWG) STATUS: variable depending on EWG, drafts to be sent to SEG in December

37. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Develop non-prescriptive guidance: 1.explanation of key concepts: SARs, read-across and categories (including sub-categories) 2.how to perform qualitative and quantitative read-across 3.how to build a category (including special cases) 4.how to justify and report the “adequacy” of a read-across or category proposal  appropriate reporting formats Task 3: Guidance on Chemical Categories / Grouping of Substances STATUS: 6 consensus chapters + >10 individual appendices Submission to SEG on December. Being integrated in Task 1 Results being Merged in Task 1

38. European Chemicals Bureau Croatia-JRC-ECB InfoDays, 11-13 December 2006 Task 4 – Preparation of draft TGD Specific objective: To combine all the input from the Working Groups into the overall Technical Guidance Document Deliverables: –final draft of the Technical Guidance for RIP 3.3 Status: Task 1 Drafting Group is already engaged in defining the structure and generic content of the overall TGD Information Requirements, liaising with RIP 3.2 to ensure compatibility. To be developed mainly in 2007. All package expected to be delivered by April 2007