Global advances in risk assessment and governance - The calibrate Approach

Transcription

1 Global advances in risk assessment and governance - The calibrate Approach Coordinator, Professor Keld Alstrup Jensen, Ph.D., cand.scient. kaj@nrcwe.dk Project #686239, Funded by the Horizon 2020 Framework Programme of the European Union

2 How to understand governance Ship in the Ocean (System in a Context) Stakeholders (Passengers, Crew, Habour, Fish ) Engine (RA-, RM-, DS-, communication Tools) Rodder, Power control, Anchor... (Means) Chief mate, Captain (Governator(s))

3 Risk Governance Status in the EU! EU Code of Conduct (EU member states signed in 2008) Implementation NOT a success! Stakeholders (industry) generally request: exposure limits, exposure data, models (All adhere to REACH system) (e.g., Dorbeck-Young and Shelley Egan. Nanoethics (2013)

4 Stakeholders in the Nano_Risk Arena Scientists & Service Providers R&D and Industry Regulators Safety at work Administration Risk transfer Safe application Insurance Consumers and NGO s

5 Operational (hands on) Legal Responsibility Local Governance A company as example Board Director / Owner Chemical Safety Officers (nanosafety) awareness Work Leaders Worker representatives The workers Global Law Regulation Guidance Recommendations Local Rules Guidance

6 Scientists & Service Providers Stakeholders in the Nano_Risk Arena Stakeholders mainly conduct local governance!? R&D and Industry Regulators Safety at work Administration Risk transfer Safe application Insurance Consumers and NGO s

7 Current status of regulatory accepted risk assessment and management models

8 REACH Risk Assesment tools REACH Tier 1 estimates ECETOC TRA EMKG EXPO Tool ConsExpo (Risk of Derm) Stoffenmanager Advanced REACH Tool No exposure limits or official DNEL s for NM No proper emission potentials for NM No default exposure scenarios in the tools Lack of product categories for nanoproducts Gaps in application domains REACH model assessments impossible or to be done with GREAT care!

9 Exposure assessment paradigme Emission (Rate) Testing Exposure Measurement Exposure (Risk) Modelling

10 What is calibrate doing about it?

11 Who we are? Coordinator: NRCWE (KA Jensen) 24 Partners 21 from Europe (2 Switzerland) 2 from USA 1 from South Africa DIALOGIK University of Helsinki Budget ca. 9.7 Mio 8 Mio from the EC Duration: 42 Months (started May 1, 2016)

12 The project challenge! The conventional risk assessment approach, is inadequate for enabling safe use for newly developed materials in the fast moving market of nanomaterials. The risk analysis is still technically and methodologically limited and associated with a high uncertainty Build a state-of-the art and flexible risk banding tool to keep pace with developments in innovation and risk research by harvesting and implementing results from concluded, ongoing and planned research in next generation risk governance frameworks. Stakeholders' concerns, including those of the insurance sector, and risk perception should be understood and communicated. Risk acceptance is strongly affected by a clear understanding of the risks, the benefits and the uncertainties perceived on equity and trust.

13 What will calibrate deliver? A framework with tools and guidance to assist industries in the current use and further R&D of safe /welldocumented NM and NM-products Tested and documented for nanomaterials EHS control banding, risk assessment and decision support tools EHS database and guidance on risk management as and communication with company stakeholders Key 4 Nano-Risk Innovation Governance!

14 Discovery and ideas Scoping Stage 1 Build business case Research and development Testing and Validation Launch Horizon Scanning/ Monitoring Typical process during innovation of new products and implementation of new technology /$ material, product and safety knowledge Idea screen Scoping Screen Go to development Go to test Go to Launch Insure Post-Launch review Gate 1 Gate 2 Gate 3 Gate 4 Gate 5 Gate 6 EHS Cooper Stage-Gate Idea to launch model (innovation funnel)

15 Discovery and ideas Scoping Stage 1 Build business case Research and development Testing and Validation Launch Horizon Scanning/ Monitoring Emerging Risk Management (Risk Governance) [CEN Workshop Agreement (2013)] Horizon scanning / Early Warnings Pre-risk assessment Risk assessment Risk management and decision Communication and consultation Monitoring Context and concerns ID of risk scenarios Evaluation Analysis Characterization Evaluation + Idea screen Scoping Screen Go to development Go to test Go to Launch Post-Launch review Gate 1 Gate 2 Gate 3 Gate 4 Gate 5 Gate 6 Cooper Stage-Gate Idea to launch model

16 Discovery and ideas Scoping Stage 1 Build business case Research and development Testing and Validation Launch Horizon Scanning/ Monitoring What does this mean for innovation nano-risk governance Building and maintainence of confidence in the risk assessment for trustworthy risk communication and governance Idea screen Scoping Screen Go to development Go to test Go to Launch Post-Launch review Gate 1 Gate 2 Gate 3 Gate 4 Gate 5 Gate 6 Communication Monitoring and consultation Cooper Stage-Gate Idea to launch model Risk management Risk assessment and decision Analysis Characterization Evaluation Qualitative / Semiquantitative predictive Horizon scanning Pre-risk / Early Warnings assessment Context and concerns ID of risk scenarios Evaluation Quantitative predictive / Test Data Driven

17 Modelling information Stage-gate innovation funnel Discovery and ideas Scoping Build business case Research and development Testing and validation Launch Horizon Scanning/ Monitoring The calibrate Nano Risk Governance Framework Conceptually! Technical and safety information level Idea screen Scoping screen Go to development Go to test Go to launch Post-launch review Gate 1 Gate 2 Gate 3 Gate 4 Gate 5 Gate 6 Decision support Monitoring Safe-by-design Regulatory risk assessment Predictive risk assessment Pre-risk assessment Control banding and simple predicitve models

18 Work plan and current status Year Framework development Aligning with stakeholders Model development and testing Database development Collecting models Collecting of existing data 1 Conceptual framework development Stakeholder consultation Interviews and surveys Alignment with Cooper Stage Gate and stakeholder needs Operational database and structure development Sensitivity analysis and performance testing Primary test databases 2 Development of guidance documents User testing of models Refinement and next generation methods Filling data gaps and new case studies 3 Model integration into the SoS Framework Sensitivity analysis and calibration Final comprehensive databases 3.5 Demonstration using database case studies Implementation and stakeholder training

19 Investigation of Stakeholder Needs and Concerns Project #686239, Funded by the Horizon 2020 Framework Programme of the European Union

20 Key interim results from stakeholder consultations The risk assessment model needs from industry, insurance and regulators (Questinaire and workshops) The nano-risk understanding and concerns at the industry, insurance and regulators (Delphi survey) The nano-risk understanding and concerns in the public (Focus groups dialogues) Model selection and alignment with needs Stakeholder profiles and prioritization for communication

21 Example of stakeholder prioritization of effort perceived problems in nanosafety Non-experts (scale 1[v.low] 5[v.high]). Experts

22 Users model and framework needs (RA + SoS framework) Majority supports development of the calibrate framework and are interested in using such a system (focus on calibration and validation rather than new models). R&D and industries need ability to identify NM; guidance; simple, inexpensive, quick (30 min use) nanospecific RA tools (control banding); flexible along the stage gate innovation funnel. Nanospecific risk assessment methods are needed for different regulatory domains; tools needed for close-to-market RA. Industry uses typically consultants for the final (regulatory / compliance) assessment of NMs and new products when it comes to regulatory risk assessment and registration. The insurance sector is interested in the SoS, but insurance companies are not specifically concerned about the specific risks associated with nanomaterials. Difference between the approaches in insurance and re-assurance companies 22

23 What does the end-user / consumer need to know about the NM / NM-enabled product? (scale 1[v.low] 5[v.high])

24 Conceptual SoS innovation nano-risk governance Framework Nano-Risk (Innovation) Governance Interface Guidances Communication Implementation Intervention User-specific Risk Radar Risk mitigation Acceptance Avoidance Limitation Transfer Risk Management Decision support Safety-by-Design DATA & PC NM Model Based on stakeholders needs from the SoS nano-risk innovation governance framework? Integrated HRA inc Hazard Model Exposure Model Integrated Env.RA Hazard Model Exposure Model

25 Top-model selections for draft SoS Nano-Risk Governance Framework (Existing models) HRA ERA Worker Consumer DS LCA Fate / Hazard Risk Assessment DS - LCA Idea Scoping StM Nano NanoSafer CB Swiss PM SUNDS* - / NanoQSAR Swiss PM SUNDS* R&D NanoSafer CB Swiss PM SUNDS* - / NanoQSAR Swiss PM SUNDS* Test NanoSafer CB Swiss PM SUNDS** - / NanoQSAR Swiss PM SUNDS*** Validation GUIDENANO GUIDENANO SUNDS** SB4N / (n)sswd GUIDENANO SUNDS*** Launch GUIDENANO GUIDENANO SUNDS** SB4N / (n)sswd GUIDENANO SUNDS*** Monitor NanoSafer CB GUIDENANO SUNDS** SB4N / (n)sswd GUIDENANO SUNDS*** * Includes LICARA NANOSCAN, StoffenManager Nano 1.0 ** Includes Bench Mark Dose model; NanoSafer CB and ConsExpoNano exposure assessment models, Risk of Derm *** Includes nsswd

26 Sensitivity and Performance testing of the model candidates for the SoS Project #686239, Funded by the Horizon 2020 Framework Programme of the European Union

27 Next step: Testing, refinement, calibration and demonstration of tools! Models and Tools Testing test calibrate Data SoS Framework demonstrate Training and disemination

28 Webpage: See also: Thank you for your attention

29

30 What is Control Banding and how can it help? Qualitative or semi-quantitative risk assessment and management approach to minimize worker exposures to chemicals (risk factors) (structured, easy-tounderstand, practical approach). Often relatively simple with the most advanced tools comparable to Tier 1 level of e.g., REACH exposure assessment (Liguori et al., 2016). Currently several different methods Swiss Precautionary Matrix NanoRiskCat IVAM Guidance ANSES tool US Nanotool Stoffenmanager Nano NanoSafer Paik et al. (2008)

31 Parameters with overall highest and lowest (oneat-a-time) sensitivity in NanoSafer CB 1.1. Nanosafer CB Most sensitive unit Least sensitive unit 1 Dustiness mg/kg Surface coating* yes/no 2 OEL nano or bulk mg/m3 Material density** g/cm 3 3 Energy level - Water solubility g/l 4 Duration of cycle min GHS/CLP statements yes/no 5 Room size m3/h R-Phrases yes/no 6 Air exchange rate times/hour Amount used per task kg 7 Specific surface area** Pause between cycle min 8 Time per task min * In hazard ranking; **Increasingly sensitive parameter with increasing specific surface area. ** Only between NMs

32 Parameters with overall highest and lowest (oneat-a-time) sensitivity in Stoffenmanager Nano 1.0. StM Nano Most sensitive unit Least sensitive unit 1 Process domain Multiple choice duration of handling Multiple choice 2 Daily cleaning Multiple choice room volume Multiple choice 3 Monthly inspection Multiple choice room ventilation Multiple choice 4 Concentration Multiple choice 5 Handling in the breathing zone local control measures Multiple choice Multiple choice product type Multiple choice 6 Viscosity Multiple choice dustiness Multiple choice 7 Appearance Multiple choice moisture content Multiple choice 8 Frequency of handling Multiple choice dilution and handling (activity) Multiple choice

33 Key elements and information requirements in the Control Banding tools Method Number of Input parameters asked for Number of input parameters used Nanorelevance Hazard scaling Expo. scaling Number of control bands Haz. Exp. Risk ANSES CB Tool NanoSafer 1.0 # IVAM Guidance Swiss Precautionary Matrix n.a. n.a. 2 CB Nanotool Stoffenmanager Nano # The technically simplest model # The technically most advanced models Modified from Liguori et al. NanoImpact (2016)

34

35 In which areas are the perceived problems in nanosafety (scale 1[v.low] 5[v.high]).

36 Is the perceived uncertainty in the safety of NM and NM-enabled products a limitation to their diffusion on the market and their use? Non-experts Experts

37 Is the perceived uncertainty in the safety of NM and NM-enabled products a limitation to their diffusion on the market and their use?

38 In which areas are the perceived problems in nanosafety (scale 1[v.low] 5[v.high]). Public * * * *

39 What does the end-user / consumer need to know about the NM / NM-enabled product? (scale 1[v.low] 5[v.high])

40 Inhalation exposure assessment Dermal exposure assessment Inadvertent oral exposure assessment Tier 0: Risk categorization Hazard indicator X Likelyhood of exposure Hazard indicator X Likelyhood of exposure Hazard indicator X Likelyhood of exposure Tier 1: Control-banding (qualitative risk assessment) Inhalation hazard grouping X exposure potential Dermal risk hazard grouping X exposure potential Ingestion hazard grouping X exposure potential Tier 2: Basic predictive risk assessment Inhalation hazard estimate X conservative exposure model Dermal hazard estimate X conservative dermal exposure loading Ingestion hazard estimate X conservative transfer efficiency model Tier 3: Quantitative (predictive) risk assessment Data-based hazard X aerosol dynamic model Data-based hazard X NM dermal exposure loading model Data-based hazard X NM-specific transfer model / Dustiness data library PROC-USE 1 Release data library TEDIE. 2 data library Exposure Models Continuous Drop & Rotating Drum - Dustiness index - Dustiness kinetics - Spray - Mechanical wear - Mechanical reduction - Leaching -Surface to hand -Surface to glove -Hand to mouth -Hand to perioral area -Glove to perioral area 1 PROC-USE: Process and Product Use; Data based on Mackevicka and Hansen (2016) and Koivisto et al. (2017) 2 TEDIE: Transfer Efficiencies for Dermal and Ingestion Exposure v (provided by IOM). Data are not specific to NM!

41 Risk assessment model ranking along the Stage-Gate model considering users dataavailability and needs Project #686239, Funded by the Horizon 2020 Framework Programme of the European Union

42 Top models for nanospecific environmental risk assessment versus data availability and user needs ecotox Risk assessment / decision support

43 Top models for nanospecific environmental risk assessment versus data availability and user needs

44 Top models for nanospecific human risk assessment versus data availability and user needs Post analysis additions + SUNDS* + Risk of Derm*

45 Parameters with overall highest and lowest (oneat-a-time) sensitivity in Swiss PM and SB4N. Precautionary Matrix SB4N 1 Most sensitive Scores Least sensitive Scores Nano-relevance according to the precautionary matrix (N.X) Solid matrix, stable under conditions of use, NPR not mobile (E1.7) Solid matrix, stable under conditions of use, NPR mobile (E1.6) Solid matrix, not stable under conditions of use (E1.5) Redox activity and / or catalytic activity of the NPR present in the nanomaterial (W1) Stability (half-life) of the NPR present in the nanomaterial in the body (W2,A,V) or under environmental conditions (W2,U) Value of 0 or 1 Value of 0 or Value of 0 or 0.01 Value of 0 or 0.1 or 1 Value of 1, 5 or 9 Value of 1, 5 or 10 origin of the nanomaterial (S1) data availability (S2) downstream user (S3) purity of the material system (S4) Value of 0, 3 or 5 Value of 0, 3 or 6 Value of 0, 3 or 7 Value of 0, 3 or 8 dissolution rates 1/s ENP diameter nm 2 attachment efficiencies -

46 Impact of the sensitivity testing Sensitivity analysis is used to verify the function of the models with model developers Sensitivity analysis is used to identify the most critical physicochemical, toxicological and contextual input parameters Sensitivity analysis is used to assess data gaps for case-specific model performance testing and demonstration of the framework. WP5 & 6 GAP NM and exposure measurements Testing (WP7) Out if it fails Data Quality & Completeness

47 Next steps Project #686239, Funded by the Horizon 2020 Framework Programme of the European Union

48 Next steps! Year Framework development Aligning with stakeholders Model development and testing Database development Collecting models Collecting of existing data 1 Conceptual framework development Stakeholder consultation Interviews and surveys Alignment with Cooper Stage Gate and stakeholder needs Operational database and structure development Sensitivity analysis and performance testing Primary test databases 2 Development of guidance documents User testing of models Refinement and next generation methods Filling data gaps and new case studies 3 Model integration into the SoS Framework Sensitivity analysis and calibration Final comprehensive databases 3.5 Demonstration using database case studies Implementation and stakeholder training

49 Risk estimation of ahlloysite use in large laboratory assuming that the kaolinite OEL: 2 mg/m 3 is valid

50 Next step (on-going): To construct the framework and validate models Risk Innovation Governance Interface Guidances Communication Implementation Intervention User-specific Risk Radar Risk mitigation Acceptance Avoidance Limitation Transfer Risk Management Decision support Safety-by-Design PC NM Model Based on stakeholders needs from the SoS risk innovation (SbD) governance framework? Integrated HRA inc Hazard Model Exposure Model Integrated Env.RA Hazard Model Exposure Model