Deliverable D1.4 Annual Summary Report (ASR) Y1 Reporting period from 1 May 2022 to 31 December 2022

EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Partnership for the Assessment of Risks from Chemicals Deliverable D1.4 Annual Summary Report (ASR) Y1 Reporting period from 1 May 2022 to 31 December 2022 Second version EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 2/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Technical References 1 PU = Public PP = Restricted to other programme participants (including the Commission Services) RE = Restricted to a group specified by the consortium (including the Commission Services) CO = Confidential, only for members of the consortium (including the Commission Services) Document history Version Date Reviewer name/institution Short description of changes 1 21/10/2022 GB members 2 23/11/2022 GSB members 3 20/02/2023 PARC Coordination Team and MB members Clarifications given in the first version of the ASR submitted on 05/01/2023, based on the comments received from HaDEA Work Package WP1 - Coordination and Management Task Task 1.2 - Scientific steering and implementation of Annual Work Plans Dissemination level 1 Public Lead Beneficiary ANSES Contributing Participants all Participants Responsible author(s) Pascal Sanders, ANSES, [email protected], Christophe Rousselle, ANSES, Christophe.rouss[email protected] Co-authors PARC Coordination Team, ANSES, WP co-leaders, Task co-leaders Reviewers GB and GSB members Due date of deliverable 31/12/2022 Actual submission date 05/01/2023 Submission date of the second version of the ASRY1 28/02/2023 EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 3/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 List of abbreviations 3R: Reduction, Refinement and Replacement ADME: Absorption, Distribution, Metabolism and Excretion AE: Affiliated Entity AI: Artificial Intelligence ANT : Acute NeuroToxicity AO/ AON/ AOP: Adverse Outcome/ AO Network/ Pathway API: Application Programming Interfaces ASR/ AWPs: Annual Summary Report/Work Plans CA: Consortium Agreement CL/ ML: Chemical Leader/ Methodology Leader CLP: Classification, Labelling and Packaging CMS: Content Management System COPCSD: Common Open Platform on Chemical Safety Data CSS: Chemicals Strategy for Sustainability CT: ANSES PARC Coordination Team DEPB: Data and Ethics Protection Board DMP: Data Management Plan DNT : Developmental NeuroToxicity DoA: Description of Action EC: European Commission ECHA: European Chemicals Agency ED/ EDCs: Endocrine Disrupters / endocrine disrupting compounds EDA: Effect-Directed Analysis EFSA: European Food Safety Authority ERA: Environmental Risk Assessment EUSES: European Union System for the Evaluation of Substances EWS: Early Warning System FAIR: Findable, Accessible, Interoperable, and Reusable FIP: FAIR Implementation Profiles GA: Grant Agreement GB: Governing Board GDPR: General Data Protection Regulation GFF: GO FAIR Foundation GIVIMP: Good In Vitro Methods Practices GS: Grant Signatory GSB: Grant Signatory Board HA: Hazard Assessment HBM: Human BioMonitoring KEs: Key Events KPI: Key Performance Indicator MB: Management Board ML: Machine Learning MCRA: Monte Carlo Risk Assessment LCA: Life Cycle Assessment MoA: Mode of Action MIEs: Molecular Initiating Events MS: Member States NAMs: New Approach Methodologies NGRA: Next Generation Risk Assessment NHs: National Hubs NR: Nuclear Receptor NHCPs: National Hub Contact Points NGTxC : Non-Genotoxic Carcinogens NTS: Non-Targeted Screening OECD: Organisation for Economic Co-operation and Development OO: Operational Objectives PFAS: perand polyfluoroalkyl substances PFDP: PARC FAIR Data Policy BPA: Bisphenol A PBK: Physiologically Based Kinetic PBTK: Physiologically Based Toxicokinetic PEC: Predicted Environmental Concentration POD: Point of Departure PPP: Plant Protection Products PSIP: Partnership Specific Impact Pathways QA/QC: Quality Assurance / Quality Control QAWG: Quality Assurance Working Group QIVIVE: Quantitative in vitro / in vivo Extrapolation QSAR: Quantitative Structure Activity Relationship RA/RM: Risk Assessment / Risk Management R&I: Research and Innovation RRM: Rapid Response Mechanism SDGs: Sustainable Development Goals S2PD: Science-to-Policy Dialogue SAICM: Strategic Approach to International Chemicals Management SF: Stakeholder Forum SO: Specific Objectives EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 4/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 HBM GV: Health-based Guidance Values IATA: Integrative Approaches for testing and Assessment IB: International Board IPM: Integrated Pest Management IPR: Intellectual Property Rights ISES: International Society of Exposure Science IVIVE: in vitro - in vivo extrapolation JRC: Joint Research Centre SRIA: Strategic Research and Innovation Agenda SS: Suspect Screening SbD: Safe-by-Design SSbD: Safe-and-Sustainable-by-Design T/TL: Task/Task co-leaders THSD: Tyroid Hormone System Disruption THS: Tyroid Hormone System TTC: Toxicological Threshold of Concern UCWG: Use Case Working Group(s) UNEP: United Nations Environment Programme US-EPA: US Environmental Protection Agency US-NTP: US National Toxicology Program WHO: World Health Organization WP/ WPL: Work Package / WP co-leaders Definitions SRIA (Strategic Research and Innovation Agenda): For the Year 1 of PARC, SRIA is an annex of AWPY1 presenting a summary of the projects organized by WPs/Tasks/Activities. The term SRIA has been replaced from year 2 by PARC Project Portfolio. From Year 2 of PARC, SRIA will be an overarching document presenting PARC at a strategic level with PARC vision, objectives, exit strategy, a description of what has been achieved and what will be done in the next year(s) organized by specific topics related to risk assessment (monitoring, hazard, environment, mixtures…). As Annexes to the SRIA, there will be a summary map of WPs and activities to understand the connections and a list of projects organized by specific topics. SRIA will be an additional deliverable attached to the GB meeting and then reported to the Commission every year. PARC Project Portfolio: Annex of the AWP from AWPY2 presenting a summary of the projects organized by WPs/Tasks/Activities with a short description of WP/Task as an introduction. Abstract The Annual Summary Report (ASR) reflects the results of the work achieved during the calendar year. As the project started on 1 May 2022, the first ASR covers the period from 1 May 2022 to 31 December 2022 (8 months). Main achievements are briefly described below: - WP1: An effective management and governance framework is set up and appropriate tools are provided. The monitoring framework is being discussed with the relevant actors to ensure it is adapted to the objectives and impacts of PARC. The Data and Ethics Protection Board (DEPB) is in the process of being set-up and first ethics and data protection discussions are being initiated. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 5/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 - WP2: A process and criteria for project review and approval is validated and implemented for the projects included in the PARC rolling SRIA. Preliminary discussions and conceptual developments have been initiated for the development of NGRAroute and PARCopedia and task forces created to structure the future work. The framework for Chemical Leaders (CLs) and Methodology Leaders (MLs) and their nomination is ongoing. A process for continuous dialogue with the National Hub Contact Points (NHCPs) is implemented and a first survey to collect input on needs, capacity building and sustainability has been launched. - WP3: The criteria for selection and a list of potential participants in the Stakeholder Forum and International Board are identified. The initial composition of the Stakeholder Forum (SF) and the International Board (IB) has been established. The graphical identity for PARC and a PARC website landing page is being created. The web development is initiated and the PARC communication and dissemination strategy is set. The rules for the establishment of official synergies between external projects and PARC are under development. - WP4: For HBM, three working groups each focusing on one aspect of the work: i) review and update of materials; ii) areas of needs and improvements in PARC; iii) solutions for inclusion of novel aspects in HBM studies implementation, are set up. The Quality Assurance Working Group (QAWG) is created and the needs for QA and comparability of the HBM data generated are identified. Two projects linking exposure and health related information are initiated. A first inventory of existing prioritisation schemes, as a preparatory work for the development of a framework for automated assessment and prioritisation of chemicals / matrices / endpoints deserving attention for future monitoring projects is initiated. A pilot project on the monitoring of per-/polyfluorinated alkylated substances (PFAS) and endocrine disrupting compounds (EDCs) in the environment is launched. Six projects relating to the alignment of main concepts and strategical vision regarding innovative methods, definition and harmonisation of QA/QC issues for suspect screening/ Non-Targeted Screening / (SS/NTS) approaches, relevant contribution to Early Warning System, elaboration of integrated Data Processing Workflow, as well as two first proofof-concept applications focused on perinatal exposure and wastewater based epidemiology are launched. - WP5: Groups of substances with data gaps on hazard for human health and environmental health that can be closed in PARC are selected for initial studies: these include natural toxins and Bisphenol A (BPA) alternatives. Endpoints to be tested are selected and projects defined and started. Projects related to the development of innovative methods and tools for toxicity testing and modelling for non-genotoxicity carcinogenicity, metabolic disruption, endocrine disruption, immunotoxicity, and developmental neurotoxicity have been initiated, as well as for environmental toxicology / ecotoxicology of BPA alternatives. A project on prioritised New Approach Methodologies (NAM)-based mechanistic hazard characterisation and translation to human pathophysiology is defined. A core group with expertise in methods for Adverse Outcome Pathway (AOP) development, three specialty groups immunotoxicity and Non-Genotoxic Carcinogens (NGTxC); endocrine disruption; neurotoxicity and an effect markers groups have started working on inventorying available methods and four different brainstorming groups within task 5.3 are established to develop a strategy for data recovery and development of case studies to EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 6/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 address knowledge as well as conceptual gaps in vitro to in vivo extrapolation Physiologically Based Kinetic (IVIVE-PBK) models. - WP6: Four projects aimed at the development, testing and evaluation of Integrative Approaches for testing and Assessment (IATAs) for genotoxicity, endocrine disruption and liver toxicity are launched. For the first round of IATA evaluation case studies, criteria and candidate substances are identified and discussions on how to best achieve incorporation of PBK modelling results are underway. For improving integrated risk assessment, two projects on aggregated exposure assessment from multiple sources and routes of exposure for the general population and workers are launched. The project are working on inventories of realistic source-to-dose models for the general population and the inventory of occupational and general life models to estimate exposure from various sources and routes of exposure. Two projects on the refinement and development of PBPK models for human risk assessment and mixtures risk assessment have started. Initial work is launched on a strategy to perform risk assessment of mixtures organised into 3 groups of experts working on (integration of exposure data, hazard assessment and grouping chemicals into mixture assessment groups and kinetics to bridge risk assessment based on HBM data with external exposure assessment as performed by the European Agencies). Two approaches for the identification of exposure to mixtures in real-life based on human biomonitoring observations are explored to better understand co-exposure to chemicals with the same health impact. Four projects on human health impact assessment and risk indicators have been started. Case studies reviewing substance-specific Risk Assessment (RA) depending on intended use and case studies reviewing effect-specific RA are initiated, as well as a project reviewing tools, criteria, and methods used in regulatory RA. Two projects and scoping activities are launched to contribute to the development of regulatory relevant approaches and methods for chemical mixtures and three to facilitate the regulatory acceptance and practical use of new methods. Initial landscaping exercises have been carried out for the evaluation of information on substances in products and materials and how it can be integrated in enforcement activities and life cycle assessments. Concerning ecological risk assessment to protect biodiversity, five projects are defined and initiated. - WP7: The development of an integrated approach to training in FAIRification according to the three-point FAIRification framework (3PFF) and support to the WP in development of conceptual models, vocabularies and ontologies has been initiated. The PARC initial Data Management Plan is set. Data Champions and Data Liaisons, and the FAIR Implementation Taskgroup (FIT) are established and training has started. Cross-work package working group on vocabularies & ontologies is established and collaborative workflows are available both for the onboarding of new PARC projects into the FAIR processes and for the triage and identification of FAIR Data Use Cases. Inventory of major databases, repositories and other relevant sources for chemical risk assessment is underway. Discussions on PARC-relevant domain-level FAIR implementation profiles (FIP) are initiated. The first year’s data use cases on human biomonitoring datasets, monitoring PFAS and endocrine disruptors and databases of chemicals in articles enable the identification of core data hub services and the gaps to be filled. A list of inventories of different statistical approaches and computational tools suitable for / used in metaand pooled analysis is available as well as a workflow for meta-analysis task and the use cases for the scoping review on the integration and analysis of (heterogeneous) FAIR data and scoping study on uncertainty analysis are identified. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 7/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 - WP8: An inventory and review of existing tools that are currently available from existing initiatives on Safe-by-Design (SbD) (nano) and Safe-and-Sustainable-by-Design (SSbD) has been carried out and user requirements and functional specifications of the PARC SSbD toolbox are mapped out. The optimal set of parameters for selecting potential use cases to test the methodology developed by the EC and complement the use cases chosen by the EC are identified and a set of potential case studies formulated. Standardised protocols for early warning monitoring tools are under development, with a particular focus on suspect/non-targeted/Effect-Directed Analysis (EDA)-based tools, as well as methods in line with NAMs. A literature analysis of existing Artificial Intelligence (AI) systems in Early Warning Systems) EWS and the summarising overview in the context of their reliability and usefulness for chemicals prioritisation regarding toxicity is ongoing. A selection of databases with chemical structure and identifier information has been carried out and a review of existing studies for the identification of possible case studies that can be used for establishment of early warning monitoring tools and prioritisation framework for humans, environment, and products is ongoing. Concerning integrative models, an inventory of existing front-end access platforms and a critical review from the user-perspective is carried out. A case study on bisphenols (BPA and alternatives) has been selected as an initial set of use cases. A first draft of an overarching conceptual model that maps models and platforms to user requirements and RA questions is developed. - WP9: Networks of contact points for laboratory and exposure monitoring networking is established. An online survey to gather information for the catalogues on laboratory and infrastructure expertise, availability and capacities in the different fields has been elaborated. Working groups for harmonising Quality Assurance (QA)/Quality Control (QC) protocols/guidance for sampling, for chemical analysis, and in toxicity testing and toxicokinetics are established and first alignment within WP4 and 5 is implemented. An online survey to gather information on initial training needs is developed and was sent to the National Hubs Contact Points NHCPs. “Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.” EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 8/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Table of content Document history ................................................................................................................. 2 List of abbreviations ............................................................................................................. 3 Definitions ............................................................................................................................ 4 Abstract ............................................................................................................................... 4 Authors and Acknowledgments .......................................................................................... 10 Objectives........................................................................................................................... 10 1. Explanation of the work carried out per WP ................................................................. 11 1.1. Work package 1. Coordination and management ............................................................ 11 1.1.1. Task 1.1. Overall executive management and support of the Partnership ........................................ 11 1.1.2. Task 1.2. Scientific steering and implementation of Annual Work Plans ........................................... 13 1.1.3. Task 1.3. Impact evaluation and Monitoring of the performance indicators of the Partnership ....... 14 1.1.4. Task 1.4. Ethics framework ................................................................................................................. 15 1.2. Work package 2. A common science and policy Agenda................................................... 17 1.2.1. Task 2.1. Priority setting ..................................................................................................................... 17 1.2.2. Task 2.2. Knowledge management and uptake into policy ................................................................ 18 1.2.3. Task 2.3. Sustainability ....................................................................................................................... 20 1.3. Work package 3. Synergies, collaborations and awareness .............................................. 20 1.3.1. Task 3.1. Building effective interactions ............................................................................................. 20 1.3.2. Task 3.2. Communication, dissemination, and awareness ................................................................. 22 1.3.3. Task 3.3. Networking and Synergies ................................................................................................... 23 1.4. Work package 4. Monitoring and Exposure ..................................................................... 24 1.4.1. Task 4.1. Human Biomonitoring ......................................................................................................... 24 1.4.2. Task 4.2. Environmental and multisource monitoring ....................................................................... 29 1.4.3. Task 4.3. Innovative methods and tools for monitoring and surveys ................................................ 31 1.5. Work package 5. Hazard Assessment .............................................................................. 33 1.5.1. Task 5.1. Toxicity testing addressing data gaps of concern ................................................................ 33 1.5.2. Task 5.2. Innovative methods and tools for toxicity testing and modelling ....................................... 36 1.5.3. Task 5.3. Quantitative systems toxicology and development of new AOPs ....................................... 39 1.6. Work package 6Innovation in RA .................................................................................... 42 1.6.1. Task 6.1. Integrated Approaches to Testing and Assessment of Chemicals ....................................... 42 EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 9/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 1.6.2. Task 6.2. Integrative exposure and risk assessment........................................................................... 45 1.6.3. Task 6.3. Review of risk assessment methodologies .......................................................................... 49 1.6.4. Task 6.4. Transposing results to regulatory risk assessment methodologies ..................................... 52 1.7. Work package 7. FAIR Data ............................................................................................. 56 1.7.1. Task 7.1. FAIR Data Policy and implementation ................................................................................. 56 1.7.2. Task 7.2. Data libraries ....................................................................................................................... 59 1.7.3. Task 7.3. Innovative analyses ............................................................................................................. 62 1.8. Work package 8. Concepts and Toolboxes ....................................................................... 64 1.8.1. Task 8.1. Safe and sustainable by design (SSbD) ................................................................................ 64 1.8.2. Task 8.2. Scientific and technical basis for an Early warning system (EWS) on chemical risks ........... 68 1.8.3. Task 8.3. Integrative models ............................................................................................................... 70 1.9. Work package 9. Building Infrastructural and human capacities ...................................... 72 1.9.1. Task 9.1. Laboratory networking ........................................................................................................ 72 1.9.2. Task 9.2. Building exposure monitoring capacities ............................................................................ 73 1.9.3. Task 9.3. Joint activities – harmonisation ........................................................................................... 74 1.9.4. Task 9.4 Training ................................................................................................................................. 75 2. Overview manuscripts/publication .............................................................................. 76 EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 16/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 - The Deliverable D10.2 Ethic Assessment report for Year 1 (OEI - Requirement No. 2) has been submitted to the EC in June 2022. The D10.2 focuses on ethics issues related to the activities that will be implemented during the first year of PARC. - The Data and Ethic Protection Board (DEPB) is expected to be established by the beginning of 2023. The DEPB should be composed of two external experts and three representatives from the research and data-centric WPs of the partnership (WP4, WP5, and WP7). - To smoothen up the communication and implementation of data and ethics processes, all WPs have nominated an Ethics contact point. In addition, and in collaboration with WP7, Data contacts points have similarly been identified. - The Ethics Charter initiated by the PARC CT and Task 1.4 co-leaders has been prepared and disseminated amongst PARC participants. This document is intended to be a code of conduct, which highlight good practices and recommendations that should be followed by PARC participants to reduce and/or address ethical issues that may arise during the Partnership implementation. - The MB members have filled in and will maintain a Declaration of Interest annually. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays D10.2 OEI - Requirement No. 2 ANSES 31/05/2022 (M1) 13/07/2022 (M3) No significant delay MS1 Establishment of Data and Ethics Protection NIJZ/E HESP 31/10/2022 (M6) Ongoing Delayed Composition of the DEPB (the members of the DEPB will be selected by mid-February) D10.1 OEI - Requirement No. 1 ANSES 31/01/2023 (M9) Ongoing The members of the DEPB will be selected by mid-February and the report will be prepared consequently D10.3 OEI - Requirement No. 3 ANSES 31/12/2022 (M8) Ongoing Expected to be submitted by mid-February 2023 with the AWPY2. The PARC CT is collecting ethics information from the task co-leaders and project leaders to prepare the deliverable D1.5 Ethics and data protection policy NIJZ/E HESP 30/04/2023 (M12) Ongoing No significant delay expected at this stage, it will depend on the time of implementation of the board and how the interactions are made with WP7. Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: The deadline for candidates to submit their application for the DEPB has to be expanded as there were not enough candidates after the first round. Interviews will be organised in January 2023 and the official nomination will take place in February 2023. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 17/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 1.2. Work package 2. A common science and policy Agenda 1.2.1. Task 2.1. Priority setting Leader: ANSES (FR), ECHA (EU), EFSA (EU) Participants: EAA (AT), EEA (EU), UBA (DE), BfR (DE), ISS (IT), GCSL (EL), DGS (PT) Specific objective of the task for Y1: Developing and implementing a well-structured and transparent prioritisation strategy through a fluid dialogue between WP2 and other Work Packages (WPs) and making a proposal for a systematic, criteria-based prioritisation for projects and substances. Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  PARC prioritisation process including a process for project review and approval To ensure the delivery of PARC operational outcomes by the different work packages, most of the activities in PARC will be done through projects grouped and organised under the tasks/activities within the PARC work packages. In order to select projects that will be included in the rolling SRIA (Strategic Research and Innovation Agenda), T2.1 partners prepared a project review process that contains the following phases:  Initiation Phase: the project initiation request provides details on the project definition in terms of scope, data, risks and ethics and defines the partners involved in the project and the main budget requirements. The document is submitted to task 2.1 and is reviewed according to the developed criteria. The objective of the criteria is that the projects are fit for purpose so that the knowledge generated within PARC can contribute to EU and/or national regulatory science and policymaking. Further to the analysis of the relevance of the project, the projects that have been recommended through the Decision Memo submitted to the MB will enter the planning phase and will be added to the PARC rolling SRIA.  Planning phase: the project planning document specifies the project scope, the schedule for the planned tasks (which could be divided in several steps) and an estimate of the necessary resources. The document is established by the project team and once agreed and finalised, it is considered as a reference document for the project, agreed on by the partners and integrated in the PARC budget.  Implementation phase: this phase starts when the project team implements the project and produces the intermediate reports as outlined in the project plan. The monitoring process is organised by the Project Manager and the Task Leaders in close collaboration with the CT. The project implementation document will be updated each year and will be used for the production of the PARC ASR/AWP.  Closing phase: the Project Manager ensures that the final report produced is accepted by the WPLs/TLs. All project documents are correctly filled and archived and all resources used by the project are formally released. A project financial report is produced and the budget line is closed. The project ends at this date. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 18/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 An Excel file (PARC Projects cluster) with the list of the Tasks, Activities and related Projects for each WP is regularly updated on the PARC ANSES SharePoint. The Excel file also includes the names of the contact points and reviewers assigned to projects for project review during the different phases. The project review process has been made available to the consortium on 12 September on the PARC ANSES SharePoint after approval by MB. The project review process and criteria has been approved by the GB on 21st November (MS4). Projects description’s fiches have been updated according to these criteria. For Year 2, 7 new projects have been reviewed by T2.1 Contact Points and reviewers. Finally, 5 new projects have been included in PARC Project Portfolio in Annex of the AWPY2 (it has to be noted that one of these 5 new projects has been included as a new case study, part of the WP6 project P6.3.2.a_Y1_ToolsRA_SU of Year 1) and 60 projects are in the implementation phase.  Prioritisation criteria for substances and methods D2.1. Prioritisation criteria report (due date M9, January 2023) is being prepared in order to map the prioritisation criteria that have been already applied by PARC WP/Task leaders to select the compounds and methods included in the first AWP. To feed this Deliverable, a survey on prioritisation criteria for substances has been prepared. Questions are related to the following main criteria: regulatory status, hazardous properties, exposure characteristics and technical feasibility. The survey has been sent to WPLs/TLs end of October 2022 and analyses of responses have been used to draft the deliverable 2.1 by the end of November 2022. In parallel to the survey on prioritisation criteria for substances, discussions have been organised with WPLs 4-5-6 to identify the prioritisation process for methods. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays MS4 Approval of prioritisation criteria for projects ANSES 30/11/2022 (M7) 21/11/2022 (M7) Approval by GB on 21 November 2022 D2.1 Prioritisation criteria report ANSES 31/01/2023 (M9) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.2.2. Task 2.2. Knowledge management and uptake into policy Leader: BfR (DE), INSA (PT) Participants: AUTH (EL), UOB (UK) Specific objective of the task for Y1: Making conceptual developments and implementation of network and communication structure of the ad hoc network of international and external partners for EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 19/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 NGRAroute, scoping study to conceptually develop the information/knowledge management framework for PARCopedia as well as its implementation, and nomination of the Chemical Leaders (CLs) and Methodology Leaders (MLs). Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: After the start of the project in May 2022, Task 2.2 was launched and partner commitment and interest to participate in specific activities were investigated. An online kick-off meeting with Task 2.2 partners was organised on June 3, 2022. In this meeting the activities to be developed under Task 2.2 were presented to the partners, as well as the organisation structure proposed by the Task co-leaders. Key features of PARCopedia and PARCroute were identified; a table of contents for the scoping study (PARCopedia) and a pre-structure of the first strategic roadmap (PARCroute, NGRA route) were brainstormed at a physical meeting held in Thessaloniki, Greece, on 13 and 14 October 2022. During these meetings, the future work under Task 2.2 was structured into work items, and commitments to lead and/or participate in the “task forces” created to address these items under the overall coordination of the Task 2.2 co-leaders were collected from the participants. Regarding two of the deliverables of Task 2.2, i.e. a) an interim report on the progress with the NGRA roadmap (D2.3) and b) the scoping study for PARCopedia (D2.2). The collection of all the outputs from the individual task forces is planned to be complete by the end of the first annual work plan in April 2023 Until then, progress of the individual task forces will be monitored by means of regular online meetings. Procedures and Terms of Reference (ToR) for the nomination and role of Chemical Leaders (CLs) and Methodology Leaders (MLs) were developed, including a description of their tasks and responsibilities. Online meetings with the CT and partners were organised to obtain information concerning HBM4EU’s experience with the Chemical Group Leaders. The procedures and ToR were presented to and discussed with the MB at several MB meetings. An overview of the chemicals and methodologies being addressed under PARC was performed in order to identify the chemicals and methodologies proposed to have leaders. The procedures for the nomination and the ToR for the CLs and MLs were discussed by the MB. The official nomination of the CLs and MLs will take place in Spring 2023. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays D2.2 PARCopedia scoping study BfR 30/04/2023 (M12) Ongoing No significant delay expected D2.3 PARCroute roadmap 1 BfR 30/04/2023 (M12) Ongoing No significant delay expected MS9 Definition of the orientations of PARCroute BfR 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 20/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 1.2.3. Task 2.3. Sustainability Leader: INSERM (FR), NPHC (HU) Participants: DOMG (BE) Specific objective of the task for Y1: Developing a process for continuous dialogue with the National Hub Contact Points (NHCPs) on needs and a concept for capacity building, start developing an exit strategy and further developing and refining the monitoring framework with T1.3. Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: The survey focusing on the mapping of the existing knowledge gaps, requests, suggestions and expertise of the NHs was elaborated and launched during the second semester of 2022. This survey was applied to involve the NHs in the identification of PARC activities that need to be sustainable. Together with WP9, the basis of the peer-to-peer learning process were elaborated. Along the same lines a survey on the exit strategy was prepared and launched after that of the NH. The partners involved in this task first identified the major activities in PARC that need to be sustainable and included these in the survey. The survey is sent to the NH and asks them to prioritize the activities carried out in PARC that need to be sustained. HBM and the corresponding laboratory network have already been prioritized in HBM4EU, and it will obviously remain a priority for PARC. The other activities cover most of those of PARC, but they need to be prioritized by the NH and this task will then focus on those prioritized activities. The following activities are listed in the survey: environmental monitoring (taking into consideration current monitoring activities that are routinely carried out), non targeted screening activities both on human samples and environmental samples (taking into account the progress made in HBM4EU, other EU networks and the EIRENE ESFRI), New Approach Methodologies (NAMs) that are both developed in PARC but also in other EU clusters such as EURION and ASPIS; computational toxicology such as PBTK and AOP development, safe by design tools that are currently developed in PARC and in other EU projects, risk assessment activities and the national hub networks. Based on the survey outcomes, priorities will be identified and possibly other activities will be added and considered. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: Not Applicable. Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.3. Work package 3. Synergies, collaborations and awareness 1.3.1. Task 3.1. Building effective interactions Leader: EAA (AT), AUTH (EL) Participants: ANSES (FR), AGES (AT), EEA (EU), UBA (DE), IUSS (IT), LNS (LU), STAMI (NO), FMUL (PT), INSA (PT), APA (PT), NIB (SI), NKUA (EL), UOC (EL), GCSL (EL) EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 21/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Specific objective of the task for Y1: Setting up and running the International Board (IB) and Stakeholder Forum (SF), ensuring the representativeness of stakeholders from different sectors in the SF and that a high level IB is formed and, if relevant, assigning the PARC Ambassador. Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A3.1.1. Establishment and running the Stakeholder Forum The first Stakeholder Forum (SF) meeting is scheduled online in early 2023. The task co-leaders from EAA are responsible for the preparation and set up of the annual SFs. A kick-off meeting with Activity 3.1.1 partners took place to start the work on the establishment of the SF. Several meetings were held in order to develop and discuss the criteria to select stakeholders (Partners, MB, NHC) and to prepare the open call for membership in the PARC SF. The process was presented at a MB meeting and the feedback received was integrated in the document including the selection criteria. Finally, an open Call was distributed in October. A timeline for the activities proposed to conclude the selection of SF members and for information and approval of the proposed SF members by the MB and the GSB (December 2022) was developed. Codesign of Online SF event together with partners (agenda (tour-de-table, get-to-know, memorandum of understanding for SF participation, etc.), communication and management of registration of SF members) was performed (November and December 2022).  A3.1.2 Establishment and running of the International Board (IB) The criteria for selection of the IB members were prepared in cooperation with the partners involved and was presented at a MB Meeting for endorsement. In addition, the rules of procedure of the IB were also completed. Concerning the IB, a list of potential participants was prepared, according to their recognised expertise and high-level functions and an invitation was sent, including a previously prepared CV template. An algorithm was used to evaluate the candidates based on the CV provided and a list of potential members of the IB, together with the rules of procedure, was presented to the MB, and the GSB for approval. The first IB Meeting started to be prepared and is planned to be held in the first trimester of 2023. Strategies to manage the expectations from PARC and the IB members and maximise their inputs were discussed with the partners in order to be presented and discussed at the first meeting. Deliverable 3.3 was prepared for submission at M9. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays MS5 Establishment of SF, IB EEA/AUTH 31/01/2023 (M9) Ongoing No significant delay expected D3.3 Report on the establishment of the interactions with SF IB and ambassadors EEA/AUTH 31/01/2023 (M9) Ongoing No significant delay expected EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 22/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.3.2. Task 3.2. Communication, dissemination, and awareness Leader: EEA (EU), NPHC (HU) Participants: ANSES (FR), SpF (FR), EAA (AT), AGES (AT), UMIT (AT), VITO (BE), DOMG (BE), CIPH (CR), MOH-CY/SGL (CY), MU (CZ), HB (EE), TTL (FI), UBA (DE), BfR (DE), UI (IS), MOH-IL (IL), ISS (IT), UNINA (IT), RSU (LV), NPHSL (LT), LNS (LU), RIVM (NL), NIPH (NO), STAMI (NO), NIOM (PL), FMUL (PT), INSA (PT), APA (PT), ENSP (PT), UAVR (PT), SZU (SK), JSI (SI), NIB (SI), NIC (SI), NIJZ (SI), ISCIII (ES), KEMI (SE), SLV (SE), FOPH (CH), UKHSA (UK), UOB (UK), AUTH (EL), EFET (EL), NKUA (EL), UOC (EL), BPI (EL), GCSL (EL) Specific objective of the task for Y1: Developing and implementing the communication strategy for PARC Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: The graphical identity for PARC was produced based on ideas previously collected and discussed with the MB and the CT. It includes, among others, the logo package, graphic rollouts, templates and visual guidelines. A company contracted by EEA upon negotiated procedure, gave support with the branding, interactive media design and communication support services for PARC. Development of the PARC website: The navigation menu was drafted and discussed with the CT and all WP co-leaders. A service request was claimed at EEA and the web development was started in December 2022. Deliverable 3.2 on the PARC communication and dissemination strategy was prepared with the partners involved and submitted in due time (beginning of M7). A working group on risk communication was set up and a literature search was performed to establish a common strategy on risk communication. A roadmap for the activities was prepared and discussed. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays D3.1 PARC website EEA 31/07/2022 (M3) Ongoing This deliverable was delayed due to constraints with the procurement procedure to subcontract external services to design and develop the website. It has been internally shared with PARC participants by the end of December 2022 (M8). A first version of the PARC website will be launched in January 2023 (M9). EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 23/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 D3.2 Communication and dissemination strategy NPHC 31/10/2022 (M6) 09/11/2022 (M7) No significant delay MS8 Development of the overall architecture for information sharing VITO 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: The procurement procedure took more time than it was foreseen. EEA could not initiate the necessary procurement procedures for subcontracting of external services until the receipt of the amount of prefinancing (as of 23 August 2022) due to the constraints of the EEA financial regulation. 1.3.3. Task 3.3. Networking and Synergies Leader: INSA (PT), NKUA (EL) Participants: ANSES (FR), MU (CZ), UBA (DE), FMUL (PT), APA (PT), ENSP (PT), UAVR (PT), JSI (SI), NIB (SI), NIC (SI), NIJZ (SI), EFET (EL), UOC (EL), BPI (EL), GCSL (EL) Specific objective of the task for Y1: Exploring and establishing collaborations and synergies with other relevant scientific/regulatory/policy initiatives at national, EU and international level. Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: The rules for the establishment of an official synergy between external projects and PARC were created. The procedure was discussed among the partners of T3.3. In total, three web forms were created 1) The first form will be used for the expression of interest by external projects/activities to collaborate with PARC; 2) The second form will establish synergy with clear goals and timeline after the approval of the WP and task co-leaders; 3) The third form will contribute to the evaluation of the efficiency of the synergy and of the satisfaction of the external partners. The forms will be made available on PARC’s website. The aim is to map the synergies in a database and stimulate the cooperation with external projects by proposing further collaborations when possible. Moreover, the forms aim to create quantitative measures of the performance of PARC regarding synergies. The monitoring procedure is expected to demonstrate the effectiveness of PARC in acting as a central project for bringing together other EU projects and activities. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 24/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 D3.4 Database and roadmap for SYNnet INSA/NKUA 28/02/2023 (M10) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.4. Work package 4. Monitoring and Exposure 1.4.1. Task 4.1. Human Biomonitoring Leader: VITO (BE), ISCIII (ES) Participants: ANSES (FR), AU (DK), AUTH (EL), BPI (EL), CEA (FR), CSIC (ES), EAA (AT), EHESP (FR), FFA (FI), TTL (FI), FISABIO (ES), FOPH (CH), HSE (UK), KI (SE), IMROH (HR), INRAE (FR), INRS (FR), INSA (PT), INSERM (FR), INSST (ES), IOM (UK), IPA (DE), KUM (DE), ISS (IT), ISSeP (BE), IVL (SE), JSI (SI), KU Leuven (BE), LNS (LU), LSMU (LT), MOH-CY/SGL (CY), MOH (IL), MU (CZ), MUI (AT), MUW (AT), NIJZ (SI), NIOM (PL), NIPH (NO), NLZOH (SI), NPHSL (LT), ONIRIS (FR), UKHSA (UK), PIH (BE), REGIONH-RH (DK), RSU (LV), RUMC (NL), SCIENSANO (BE), SLU (SE), SpF (FR), STAMI (NO), SZU-CZ (CZ), SZU-SK (SK), THL (FI), UAntwerpen (BE), UBA (DE), UGent (BE), UGR (ES), UH (BE), ULFFA (SI), ULPGC (ES), ULUND (SE), UMU (SE),UMIL (IT), UNINA (IT), UNIPD (IT), UNISANTE (CH), UNIVIE (AT), UNN (NO), UOULU (FI), UOC (EL), UPV/EHU (ES), USI (CH), UU-IRAS (NL), WULS-SGGW (PL), CIPH (HR), SHSO (CY), SDU (DK), Fraunhofer-IBMT (DE), UFZ (DE), NPHC (HU), UI (IS), VSCHT (CZ), EASP (ES), SECO (CH), Specific objective of the task for Y1: Finalising study design and developing supporting materials for the general population survey, targeted surveys and occupational surveys, identifying exposure and effect biomarkers, proposing innovative (sampling) techniques for Human Bio-Monitoring (HBM) surveys and elaborating a roadmap to explore the links between prioritised exposures and health outcomes Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A4.1.1 Design, alignment and fieldwork of HBM studies The ultimate goal of this activity is to perform a range of overarching activities to promote the optimal use of supporting common materials conducive to comparable EU HBM data. The initial focus is placed on the update and further elaboration when needed of the materials developed in HBM4EU. We have established 3 working groups (WG), each focusing on one aspect of the work: i) review and update of materials (Fraunhofer, LNS, CIPH, EAA, EASP, IMROH, INSA, ISCIII, ISSeP, ISS, JSI, PIH, RSU, SpF, STAMI, UBA, ULUND, UPV/EHU, UOULU); ii) identify and address areas of needs and improvements in PARC (SpF, IDAEA-CSIC, CIPH, FOPH, Fraunhofer, EASP, IMROH, INSA, ISCIII, ISSeP, JSI, LNS, LSMU, NIJZ, NIOM, PIH, RSU, STAMI, THL, UBA, UMU, UOULU); iii) explore and propose solutions for inclusion of novel aspects in HBM studies implementation (ISCIII, SpF, CIPH, EASP, INSA, JSI, LNS, MUW, NIJZ, PIH, UBA, UMU, MOH-IL). Priority have been set in the first WG around the update of the informed consent in line with GDPR and the format-lay out of the forms for the general and occupational surveys. The second WG will define a minimal set of obligatory EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 25/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 questions and refine the questions considering the research and policy question and the mandatory variables in collaboration with 4.1.4 – data management. Solutions for the digitalisation of collection of information will be explored by the third WG who will provide guidance documents to inform the choices in the use of secure web applications for managing online surveys and databases. Projects progress (as described in the AWP1 SRIA): S4.1.1.1. Development of supporting materials for harmonized EU HBM conduct No project submitted at present S4.1.1.2 General population survey  P4.1.1.2.a_Y1_GenHBMSurvey_VITO: The general survey design has been developed by a core group of partners. Task 4.1 partners are contacted to collect information on planned HBM studies to check if they fulfil the study design criteria to contribute to the PARC general survey. First selection of studies is performed (to be finalised early 2023). S4.1.1.3. Targeted Surveys No project submitted at present S4.1.1.4 Occupational surveys  P4.1.1.4.a_Y1_OccupFeasability_TTL: Cd, PAHs and BPA were selected as priority substances for this study. General population surveys which have collected data on these substances have been identified. The study owners were approached during October to evaluate the available information on participants occupations and their willingness to share the data with the research group. Altogether 12 potential studies were identified for further evaluation. Final selection of studies will be made by beginning of March. This is followed by the identification of relevant occupational groups, coding of occupations and data analyses.  P4.1.1.4.b_Y1_SentinelSystem_KULeuven: A mapping exercise was performed among the participating countries (KUL, INSA, MU, UGR, AU, LNS, RUMC, DPH-UNINA, SpF, BPI; no answers from NIOM, ULUND, RSU and UNISANTE yet) to map in detail which institutes could contribute via sample collection, and which would only be able to contribute via questionnaires. Later on it was decided that the Sentinel Surveillance Project would not be embedded within the general survey, so that no samples could be collected, and all institutes would only collect questionnaire data. .  P4.1.1.4.c_Y1_HealthCareSurvey_TTL_RUMC: The outline of the occupational healthcare project was defined together with TTL, MU, ENSP, INRS, LNS, RUMC, ISS, UNINA, UMIL, UNIPD, RSU, SGGW, IOM, identifying the aims and scope of the project. The project will focus on hazardous medicinal products, inhalation anaesthetics and disinfection/cleaning products (biocides). So far, specific substances suitable for biomonitoring have been identified from each of these three groups. These include 12 cytotoxics, 5 anesthetic substances and 2 disinfectants. Further selection is made before M12 on the basis of the information received from hospitals regarding the most commonly used substances. These exposures will primarily be studied in hospital settings in 10+ EU member states. Potential biomarkers of exposure were identified. Relevant effect biomarkers applied in the study will be decided in collaboration with P4.1.3.3a (Roadmap to explore the links between prioritized chemical substances exposure and health concerns). Supporting occupational hygiene measurements were identified with RUMC, TTL, ISS, UNINA, MU and INRS. Partners have expressed their initial interest to be involved EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 32/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 ISCIII (ES), ISS (IT), IVL (SE), JU (CZ), KUM (DE), LNE (FR), NIB (SI), NIJZ (SI), NILU (NO), NIOM (PL), , OFB (FR), , STAMI (NO), SU (SE), SYKE (FI), THL (FI), TNO (NL), UG-AT (AT), UG-PL (PL), UKCEH (UK), UL (LV), ULFFA (SI), UNIADBN (UK), VSCHT (CZ), WULS-SGGW (PL) Specific objective of the task for Y1: Fostering the permeability and harmonisation between the environment-food-HBM communities and prioritised strategic development of innovative approaches from sampling to suspect/non-targeted/Effect-Directed Analysis (EDA) driven exposure data generation and related data processing Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: Six projects have been elaborated in year 1, in line with the roadmap established for task 4.3., which were primarily designed by the co-lead teams. These projects were then all started as planned, under the lead of the respectively appointed project leader teams.  A4.3.1 Transversal actions Projects progress (as described in the AWP Y1 SRIA):  P4.3.1.a_Y1_T01-Concept Paper_MU: this project relates on alignment of main concepts and strategical vision regarding innovative methods.  P4.3.1.b_Y1_T02-QAQC Issues_WR: this project relates to definition and harmonisation of QA/QC Issues for SS/NTS/EAD approaches  P4.3.1.c_Y1_T03-EWStools_SLU: this project relates to relevant contribution to Early Warning System  P4.3.1.d_Y1_T04-Data Processing Worflow_EHESP: this projects relates to the elaboration of integrated Data Processing Worflow  A4.3.2 Human samples based proof-of-concepts Projects progress (as described in the AWP Y1 SRIA)  P4.3.2.a_Y1_H01-Perinatal exposure_INRAE: this project relates to two first proof-ofconcept applications focused on perinatal exposure  A4.3.3 Environment samples based proof-of-concepts Projects progress (as described in the AWP Y1 SRIA)  P4.3.3.a_Y1_E01-Wastewater based epidemiology_UFZ-UBATH: this project relates to wastewater based epidemiology  A4.3.4 Food samples based proof-of-concepts No project submitted at present Formation of those project groups was addressed based on expressions of interest and expertise, and permitted to embed the majority of partners interested to contribute to the task. Most of the corresponding project kick-off meetings were organised and the further refinement and co-built detailed description and structuration of these projects are in progress EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 33/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays AD4.6 Concept paper regarding common definitions and short to medium term support to policy objectives of innovative (self-) sampling, suspect screening and NTS/EDA approaches INRAE/VUA 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: Difficulty to cope with requests from new partners willing to contribute in the task, and who were not initially included as contributors to the task, and to manage both capacity building and respect of common rules established for partner consultation and integration. Difficulty to have a consolidated vision on partner’s allocated resources due to discrepancies between budget data expressed by individual partners to the task co-lead teams and budget data as aggregated at their institutional level and possibly top-down adjusted at WP and/or whole project coordination level. 1.5. Work package 5. Hazard Assessment 1.5.1. Task 5.1. Toxicity testing addressing data gaps of concern Leader: NIPH (NO), INSA (PT), BPI (EL) Participants: Activity 5.1.1: ANSES (FR), AUTH (EL), AfR (DE), BPI (EL), CNRS (FR), IBMT (DE), IMR (NO), INRAE (FR), INRS (FR), INSA (PT), ISCIII (ES), ISS (IT), LIH (LU), MUI (AT), NIB (SI), NIPH (NO), NVI (NO), Sciensano (BE), STAMI (NO), TTL (FL), ULFFA (SI), UMIL (IT), UNAV (ES), UNIVIE (AT), WU-TOX (NL) Activity 5.1.2: BfG (DE), BPI (EL), CNRS (FR), EAWAG (CH), IEP-NRI (PL), IISPV (ES), INERIS (FR), MU (CZ), MUI (AT), NIB (SI), NIC (SI), NIVA (NO), SDU (DK), SLU (SE), UAntwerpen (BE), UAVR (PT), UFZ (DE), UG-PL (PL), UGent (BE), UPO (ES), UU (SE) Specific objective of the task for Y1: In order to close regulatory/policy data gaps on hazards, our steps in Y1 have been: i) to gather regulatory/policy needs from EU and national agencies on BPA alternatives and test item availability for prioritised groups of compounds. This was achieved through the organization of a workshop with key stakeholders (M1-4; AD5.1); ii) planning OECD test guideline studies to be conducted in years 2 and 3 (e.g. Extended One-Generation Reproductive Toxicity Studies (EOGRTS) (AD5.2)) and iii) conducting first in vitro studies on prioritised substances (M5-12). Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 34/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1  A5.1.1 Closing data gaps of concern for human health Natural toxins were selected at the beginning of PARC as a group of substances of priority with data gaps on hazard for human health that can be closed in PARC. Analogues from the Enniatins and Alternaria mycotoxins were selected to close data gaps on genotoxicity, endocrine disruption, immunotoxicity and some other selected hazards. Sourcing of the test items is ongoing. It is considered important that as much as possible the same batch of test item are used in the different studies. The first batches of test items are expected to be available late 2022. Two review papers are in preparation summarising the available data and identify data gaps. For the first round of studies, aiming at closing regulatory/ policy data gaps on hazards, substances were selected through consultation with partners involved in hazard and risk assessment in national and European Agencies (2022 06 17 BPA Alternative/Analogues dedicated workshop, AD5.1). Concerning the BPA alternatives that will be assessed to close data gaps on human health hazard, several priority substances were identified and are indicated in the Table 1, below. However, not all substances will be assessed for all endpoints and the inclusion of other alternatives/analogues outside the priority list is also be considered for specific endpoint, as was duly justified in light of knowledge gaps for specific endpoints. Table 1. List of Prioritised BPA alternatives and analogues Furthermore, there have been ongoing planning of OECD test guideline studies to be conducted in years 2 and 3 (e.g. Extended One-Generation Reproductive Toxicity Studies (EOGRTS)). Project progress (as described in the AWP Y1 SRIA):  P5.1.1a_Y1_Toxins_Bfr_UNIVE: in this project, data gaps on subforms of the mycotoxins Enniatins and Alternaria for human health will be closed. A number of discussions were held to EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 35/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 agree on a program of studies for genotoxic, endocrine disruption, immunotoxicity and selected other hazards. Sourcing of test items is ongoing. It is considered important that the same batch of test item is used in all the studies. Two review papers summarising the existing knowledge and data gaps are in preparation.  P5.1.1.b_Y1_BPA_Human tox: in this project, a meeting with stakeholders was organised to select the most relevant BPA analogues/alternatives for further testing (AD5.1). The selected chemicals will be tested for non-genotoxic carcinogenesis, endocrine disruption, immunotoxicity, developmental neurotoxicity, toxicokinetics and metabolism. Meetings to agree on a final program of studies are ongoing. One or two review papers summarising the existing data and data gaps are in preparation  A5.1.2 Toxicity assessment addressing data gaps of concern (Environment) Based on the prioritisation procedure followed within PARC, two groups of substances were selected for testing during the first years of the PARC in order to fill in the identified data gaps of concerns as regards the environmental health, i.e., naturally occurring toxins and BPA alternatives (AD5.1), therefore two projects were planned and during the first months of PARC implementation of these projects were developed in more detail and additional partners were included. Projects progress (as described in the AWP Y1 SRIA):  P5.1.2.a_Y1_NaturalToxinsAqua_Ugent project initial discussions on the selection of the natural toxins to be tested were carried out and UAVR joined as partner. Each partner will focus on specific organisms, but to ensure maximum data gap filling and impact, the selection of compounds will be streamlined between partners as much as possible. For the selection of the compounds, the environmental relevance of certain toxins as well as the exposure through food was considered. A first list of identified potential candidate compounds to be tested was created (i.e., microcystin, nodularin, yessotoxin, brevetoxin, okadoic acid) and further discussions will be carried out in the following period in order to finalise the list of individual compounds to be tested during Y2.  P5.1.2.b_Y1_BPAalternatives_BPI_MU project, a workshop was organised and the regulatory and policy needs were discussed by the EU agencies and key stakeholders (2022 06 17 BPA Alternative/Analogues dedicated workshop, AD5.1). As an outcome of this workshop a list of BPA alternatives was provided for which data gaps were identified as regards their possible adverse effects for human and environmental health. In parallel a literature search was carried out to collect monitoring data on environmental realistic concentrations of BPA alternatives as detected in different environmental compartments i.e., surface water, soil, sediment. The collection of monitoring data is currently on going. Finally, a review is under preparation in order to collect the available data and describe the identified regulatory gaps and needs. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 36/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 No. Title Leader Due date Actual Delivery date Explanation related to delays AD5.1 New tittle: Additional Deliverable AD5.1 List of prioritized BPA alternatives for WP5 Hazard Assessment activities Workshop Report WP5 (Previous tittle: Report on the workshop organised with national and EU agencies and stakeholders on the of-concern bisphenol A alternatives) BPI/NIPH/INSA 31/012023 (M9) Ongoing No significant delay expected AD5.2 Report of the description of the EOGRT study to be conducted BPI/NIPH/INSA 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: We experienced the common challenges when making e.g., 27 partners align in one project with very tight timelines. Specifically filling in all templates on time, but we are happy to apply different strategies and deliver the documents on time. We have a problem with identifying project leaders among the PARC partners for the BPA projects since this role is still not clearly defined and the most relevant people are very busy. Sourcing of test items might be challenging and some partners cannot hire personnel since contracts between the GS and the AEs are not finalised. However, the WP5 co-leaders found a solution to solve the issue. 1.5.2. Task 5.2. Innovative methods and tools for toxicity testing and modelling Leader: DTU FOOD (DK), VUB (BE); 5.2.2: MU (CZ) Participants: Activity 5.2.1: AIT (AT), ANSES (FR), BfR (DE), DTU (DK), IfaDo (DE), INRAE (FR), INSA (FR), INSERM (FR), IRAS (NL), IRFMN (IT), ISCIII (ES), IUF (DE), LIH (LU), MUI (AT), NIB (SI), NILU (NO), NIPH (NO), NMBU (NO), NPHC (HU), RIVM (NL), SDU (DK), TiHo (DE), UAntwerpen (BE), UFZ (DE), UIBK (AT), UKHSA (UK), UKL (DE), UKON (DE), UL-LACDR (NL), ULFFA (SI), UNAV (ES), UU (SE); VUA (NL), VUB (BE), WSFR (NL) Activity 5.2.2: BfG (DE), BPI (EL), CNRS (FR), EAWAG (CH), IEP-NRI (PL), IISPV (ES), INERIS (FR), MU (CZ), MUI (AT), NIB (SI), NIC (SI), NIVA (NO), SDU (DK), SLU (SE), UAntwerpen (BE), UAVR (PT), UFZ (DE), UG-PL (PL), UGent (BE), UPO (ES), UU (SE) Specific objective of the task for Y1: Developing innovative methodologies that will directly aid chemical hazard identification, Risk Assessment (RA) and regulation/policy. WP5 will focus on five different endpoints (immunotoxicity, non-genotoxic carcinogenicity, (developmental) neurotoxicity, endocrine disruption (thyroid) and metabolic disruption). EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 37/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A5.2.1 Innovative methods and tools for toxicity testing and modelling Project progress (as described in the AWP Y1 SRIA):  P5.2.1.a_Y1_NGTX_BfR Project work related to the development of tests that can identify tissue and substance specific effects related to distinct aspects of non-genotoxic carcinogenesis have been initiated. During the first 6 months, all the available assays and cellular models available at the different partners’ laboratories were listed. The most suitable assays to be conducted notably to avoid redundancy between labs were defined (needed for AD5.3). Currently, the list of NGTXCs chemicals to be tested to analyse the accuracy of the different assays is worked on (INRAE, BfR, ANSES, INSERM, NIB, UL-LACDR, UNAV, IRFM, RIVM, UKHSA, UKL, NILU).  P5.2.1.b_Y1_MD-EDC_INRAE The development of a battery of metabolic disrupting chemicals (MDC)-specific NAMs based on human as well as non-human models has been initiated. This work includes a comprehensive exploration of Nuclear Receptor (NR)-driven effects using stably transfected cell lines, NAMs encompassing hepatic and non-hepatic in vitro systems including multi-tissue cross-talk, a deep mechanistic exploration of key cellular pathways using human in vitro models, as well as parallel additional 3R-compliant models and novel methods, including imagery (needed for AD5.3). Synergies with ongoing projects such as the EURION cluster have been identified, the spectrum of MDC has been extended and there was active participation in the selection process of PARC priority-listed families of substances (INRAE, BfR, INSERM, UU-IRAS, UAntwerpen, UU, UIBK, UFZ).  P5.2.1.c_Y1_EDThDisruption_DTU Most partners (some will start only in Y2 or are in the phase of hiring personnel) have initiated their activities. After the ED-Thyroid kickoff meeting (3 June), a mapping of the activities of the different groups to the existing Tyroid Hormone System Disruption (THSD) AOP network has been established by individual project partners responding to activity map created by UAntwerpen (needed for AD5.3). Other work done so far includes the planning of the in vitro and in vivo studies as well as the multiorgan and cross-species transcriptomics studies, exploration of data sets relevant for QSAR-modelling (e.g. TTR), molecular docking simulations of human Thyroid hormone Receptor beta (hTRb) agonists and antagonists, characterisation of the evolutionary conservation of the Thyroid Hormone System (THS) axis in relation to invertebrates and non-mammalian vertebrates, literature review to extrapolate THSD from fish/amphibians to mammals/humans based on the existing cross-species AOP network. The proposal to publish the ‘ED-Thyroid project’ for publication in a Special Topic in Frontiers in Toxicology has been accepted and writing is ongoing (DTU, VUB, BfR, SDU, UAntwerpen, UFZ, VUA, ISCII, INSERM).  P5.2.1.d_Y1_Immunotox_INSERM The activities of partners have been organised in three groups: respiratory sensitisation (MUI, NPHC, RIVM), immunosuppression (INSERM, NIPH, INSA, LIH) and NAM development (IRAS, UL-FFA, INSA, UFZ, WFSR), reflecting different key events in immunotoxicity. This organisation is in line with that of Activity 5.3.2 on AOP development, thus ensuring coherent work across the two activities. Activities related to the set-up of in vitro systems that allow the assay of key events in the immune EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 38/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 system function or dysfunction have been initiated. Experimental models have been defined, discussed by all partners in dedicated workshops and SOPs are under preparation (needed for AD5.3). We had 5 workshops for the full projects (4th July, 30th August, 8th Sept, 12th Oct, 5th Dec 2022), each one consisting in presentations and discussions by the different partners. Each workshop lasts 2h at least. In addition to the global projects meetings, each subgroup (response sensitization, immunosuppression, NAM development in immune system) had more targeted meetings on a regular basis. Chemicals to be used in each assay have been identified and they correspond either to model chemicals or the priority chemicals identified in WP5. As soon as suppliers will be identified, chemicals will be purchased and experiments will start.  P5.2.1.e_Y1_Neurotox_UFZ_IUF_UU Regulatory testing for acute neurotoxicity (ANT) or developmental neurotoxicity (DNT) is currently performed in mammals (OECD TG #424, 426). We seek to develop, evaluate and implement new approach methods (NAMs) for DNT or ANT that, based on the mode of action of toxicants, inform on safe chemical concentrations. In WP5.1, established DNT/ANT assays with sufficient readiness will be used for chemical testing (i.e., BPA analogs, mycotoxins, PFAS). P 5.2.1 We focuses explicitly on the development of new assays that fill critical gaps in the existing DNT/ANT in vitro test batteries (IVB). Action 1 comprises the development of NAMs for detection of ANT. In the reporting period, we collected information on the partners’ acute neurotoxicity (ANT) assays, assay readiness levels and ANT modes of action. Action 2 seeks to fill gaps in the existing DNT in vitro test battery (DNT IVB). Here, we collected information on the partners’ DNT assays and readiness levels. The assay list is being used to design a comparative study on performance, sensitivity, specificity and redundancy of DNT test methods. With regard to chemical selection, candidate model compound lists from consortium member projects and via interaction with ASPIS cluster EU projects have been assembled and a semi-automatic workflow was prepared to compile candidate compounds with physico-chemical, structural and toxicological properties. Action 3aims to develop zebrafish assays to complement DNT and ANT IVBs. In the reporting period, we collected information on the partners’ zebrafish ANT/DNT assays and assay readiness levels. We took a key decision that, as the zebrafish light/dark transition test is undergoing an OECD ring study, P5.2.1e will focus on the development, evaluation, and use of novel DNT/ANT zebrafish assays. Novel endpoints include: learning, memory, startle response, social interaction, place preference, and anxiety-like behavior, and neuroendocrine system plasticity. The same chemical selection criteria applied to Action 2 will be used here (INSERM-UBX, UU, NIPH, IUF, UKON, RIVM, UFZ, ISCIII, TiHo, AIT, NMBU).  A5.2.2 Innovative methods and tools for toxicity testing and modelling for Environmental Toxicology / Ecotoxicology This activity has been developed during Y1 jointly with P5.1.2.b_Y1_BPAalternatives_BPI_MU, since both focus in the environmental aspect. The project has two main activities, one focuses on filling data gaps (5.1.2) and another one on NAMs development (5.2.2). The two activities have in common to study BPA alternatives on environment. Activity 5.2.2 is focused on the development of the new methodologies that cover a broad spectrum of approaches from in silico to in vivo and the spectrum of studied endpoints (e.g., neurotoxicity, oxidative stress, immunity, development, reproduction, behavioral, metabolisms and endocrine disruption among others). During Y1, partners’ information on NAMs were collected and discussed to identify synergies and overlaps. In addition, to identify BPA alternatives that will be suitable for the development of specific NAMs, experts have been working on a review summarising the toxicity of the BPA alternatives EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 39/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 identified from the BPA alternatives priority list (AD5.1). A joint meeting with Activities 5.1.1. & 5.1.2 was held, where the content and contributions of the review were discussed (11/2022). The meeting served also as a platform where 5.2.2. partners propose sophisticated studies to be conducted in years 2 and 3. In parallel, 5.2.2. is involved in an cross-task activity initiated by WP6: discussions and meetings around environment to identify synergies and overlaps. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays AD5.3 List of first assays to be developed for prioritised endpoints DTU FOOD/VUB/MU 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: The main difficulties relate to very short time that was requested to fill all necessary forms (updates of the project description, budget construction, annual summary report, annual work plan, etc.). In many cases TLs had limited chances to collect all information from all partners, specifically on cases where new information was required in forms that were available to TLs in short time before submission. For some partners, delays in contract finalisation and hence money transfer from GS to AE occur, delaying the process of hiring personnel and postponing the planned experimental work. 1.5.3. Task 5.3. Quantitative systems toxicology and development of new AOPs Leader: UL-LACDR (NL), SCIENSANO (BE), INSERM (FR), Fraunhofer-ITEM (DE) Participants: Activity 5.3.1: AUTH (EL), BPI (EL), IISPV (ES), INSERM (FR), IRFM (IT), ISCIII (ES), ISS (IT), KIT (DE), MUI (AT), NIPH (NO), NPHC (HU), Sciensano (BE), UFZ (DE), UGent (BE), UG-PL (PL), UHC (DE), UIBK (AT), UL-LACDR (NL), UMIL (IT), UNIABDN (UK), WSFR (NL) Activity 5.3.2: ACES/SU(SE), AU (DK), AUTH (EL), BfG (DE), BPI (EL), DTU (DK), IISPV (ES), INSERM (FR), IRSN (FR), ISS (IT), KI (SE), KIT (DE), KU-Leuven (BE), MUI (AT), NILU (NO), NIPH (NO), NPHC (HU), Sciensano (BE), SDU (DK), UAntwerpen (BE), UGent (BE), UG-PL (PL), UHC (DE), UIBK (AT), UL-LACDR (NL), UMIL (IT), UNIVIE (AT), WSFR (NL) Activity 5.3.3: ANSES (FR), ETHZ (CZ), Fraunhofer-ITEM (DE), IISPV (ES), INERIS (FR), INSERM (FR), ISCIII (ES), ISS (IT), NVI (NO), UHC (DE), UIBK (AT), UL-LACDR (NL), UNIVIE (AT); WR (NL), WU-TOX (NL) Specific objective of the task for Y1: i) Establishing different core or extended groups relevant for the activity of this task: omics, Adverse Outcome Pathways (AOPs), bioinformatics, effect markers, PBTK, in vivo/in vitro mode of action; ii) establishing an inventory and mapping available knowledge, reference in vivo/human datasets, activities and models in systems biology, PBTK and AOP frameworks and prioritising additional studies and iii) initiating studies to characterise coregulated gene networks, for already published AOPs (to make them quantitative) and linking chemicals to available AOPs, linking EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 40/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 omics data to human physiopathology, generating high quality ADME data and ultimately building new AOPs. Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A5.3.1 Prioritised NAM-based mechanistic hazard characterisation and A5.3.3 Translation to human pathophysiology (Systems toxicology approaches for mechanism-based chemical safety assessment). Project progress (as described in the AWP Y1 SRIA): These two activities were combined in a single project for coherence purposes:  P5.3.1.a_Y1_SystemsToxicology_UL-LACDR: In Y1, the project was further refined and several actions were defined involving different sets of partners. The actions are: to agree on data set recovery and systems toxicology tooling, coupled with a workshop on data requirement for systems toxicology; to identify and integrate Mode of Action (MoA) information using various data sources and to establish novel reference transcriptomics data sets for prioritised NAMs; to establish bioinformatics tools for systems toxicology-based hazard characterisation; to support human relevance by integrating human omics data sets, filling gaps in human pathophysiology using datasets from existing biobanks; to correlate in vitro and in vivo data on MoA with human data; to develop case studies; work on these objectives started in Y1 and will be further developed in Y2.  A5.3.2 AOP development based on integration Projects progress (as described in the AWP Y1 SRIA):  P5.3.2.a_Y1_AOPDevelopment_INSERM Different groups related to prioritised outcomes were constituted during Y1: a core group (CG) with expertise in methods for AOP development; three specialty groups (SG1: immunotoxicity and NGTxC; SG2: endocrine disruption; SG3: neurotoxicity) and an effect markers group. The groups started working by inventorying available methods, AOPs and effect markers in each topic. The CG further developed tools linking chemicals to AOP events and planned a workshop with international institutions involved in AOP development to support coordination (first trimester 2023).  A5.3.4 PBTK models and quantitative systems toxicology Projects progress (as described in the AWP Y1 SRIA):  P5.3.4.a_Y1_PBK models and quantitative systems toxicology_Fraunhofer In Y1, four different groups were established to develop a strategy for data recovery and development of case studies to address knowledge as well as conceptual gaps in IVIVE-PBK models. By this activity we will ensure that the PBK models developed in this project will be useful for the development of quantitative AOPs (a close link to 5.3.2) and also for in vitro to in vivo extrapolations (a close link to WP 6.1). Until end of 2022, a knowledge and data gap analysis are performed to develop case studies that specifically address these. The core group comprises experts in PBK modelling and/or in vitro ADME models (P5.3.4.a_Y1_PBK_Kinetics_Fraunhofer). It coordinates the selection of case study compounds EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 41/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 according to the identified data and conceptual knowledge gaps. The core group also coordinates the cooperation with WP 5.3.2 and WP6 to generate a harmonised framework for kinetic modelling. For this purpose, regular meetings are planned, once the case studies have started and results can be discussed (the first early 2023). The core groups will further reach out to other international organisations/projects driving PBK modelling, a workshop is planned for the second or third trimester in 2023. Three specialty groups (SGs) addressing PBK model approaches for the oral, or the inhalation route of exposure as well as for system toxicology have been built. An initial set of case studies has been defined. Each case study is led by one PBK modeller and one in vitro ADME expert. The planned case studies will address: impact of the human microbiome on xenobiotic metabolism and uptake; impact of isoform specific metabolism; tiered testing approach to address in vitro ADME models for inhalation exposure; PBK models for priority compounds i) Alternaria toxins; ii) Mycotoxins; iii) Enniatins; iv) BPA alternatives; iv) PFAS. Selection criteria for case study compounds include the availability of high quality in vivo ADME studies, which can be used to quantify the uncertainty of the obtained models. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays AD5.4 Inventory of omics data, biochemical data, other relevant readouts in public domain repositories for all PARC selected adverse outcomes ULLACDR,/SCI ENSANO/INS ERM/Fraunho fer 30/04/2 023 (M12) Ongoing No significant delay expected AD5.5 Inventory of the available (networks of) AOPs, prioritisation and establishment of the framework for further development in PARC ULLACDR,/SCI ENSANO/INS ERM/Fraunho fer 30/04/2 023 (M12) Ongoing No significant delay expected AD5.6 PARC Coordination Team ULLACDR,/SCI ENSANO/INS ERM/Fraunho fer 30/04/2 023 (M12) Ongoing No significant delay expected AD5.7 Draft strategy for the development of bioinformatics tools that are needed to link omics data and other mechanistic information to human relevant disease mechanisms ULLACDR,/SCI ENSANO/INS ERM/Fraunho fer 30/04/2 023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problems encountered. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 48/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 discussion between EFSA, RIVM, ANSES, BfR, EC-JRC and DG SANTE on regulatory implementation of dietary mixture risk assessment of pesticides.  A6.2.4 Human health impact assessment and risk indicators Project progress (as described in the AWP Y1 SRIA):  In P6.2.4.a_Y1_HIADataAvailability_VITO, a concise inventory was made of health impact assessments conducted for PARC priority chemicals and mixtures, based on expertise available among partners and literature search. Available external and internal exposure data and exposureeffect functions were collected as well and an overview of availability, quality and accessibility of European and national health data registries was made. First steps were made to evaluate possibilities to fill data gaps via in-silico modelling of exposures, derivation of population-specific exposures and spatio-temporal and interindividual variations, and establishment of exposure-effect associations by linking exposure, lifestyle, geographical, SES, and health status data, comparing multiple time frames, regions and populations.  P6.2.4.b_Y1_HIAMethod_UU-IRAS generated an inventory of methodologies and frameworks (including a glossary of definitions) for health impact assessment and environmental burden of disease calculations and associated uncertainties, which will form the basis for identification and planning of methodological improvements to be addressed in PARC.  P6.2.4.c_Y1_HIACaseStudies_ UU-IRAS started with definition of a framework to complete the first activities of the project, including a set of criteria for prioritisation of case studies to start in year 2, which were discussed with stakeholders, followed by a proof of concept in which the criteria were applied and a long list of case studies was proposed.  In P6.2.4.d_Y1_HIAIndicators_VITO, an inventory of existing types of risk and health impact indicators based on expertise available among partners, literature search, communication materials of (inter)national organisations, and stakeholder input (JRC and EEA for indicators related to the Chemical Strategy for Sustainability and Farm to Fork Strategy). Together with the case study prioritisation, this will form the basis for a proposal for indicator development from year 2 onwards. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays AD6.3 Roadmap on aggregated exposure strategy through different living environments sources and routes UNISANTE/ANSES 30/04/2023 (M12) Ongoing No significant delay expected AD6.4 Inventory of PBK models for assessing the internal exposure through life and for in-vitro-to-invivo extrapolation INERIS/AUTH 30/04/2023 (M12) Ongoing No significant delay expected AD6.5 Report describing co-occurrence probabilities of chemicals forming real life mixtures of the selected HBM studies across Europe and RIVM/ANSES 30/04/2023 (M12) Ongoing No significant delay expected EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 49/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 overview of the kinetic and grouping aspects of prioritised mixtures AD6.6 Inventory of existing HIA, exposure and exposure-effect data for chemicals prioritised in PARC VITO/UU 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: Some part of the work of the projects P6.2.1.a_Y1_SourcetoDose_VITO, P6.2.1.b_Y1_Aggregate_Anses, P6.2.4.b_Y1_HIAMethod_UU-IRAS and P6.2.4.d_Y1_HIAIndicators_VITO and some partners have started later because of financial and recruitment problems to involve staff to help leaders work on the projects. 1.6.3. Task 6.3. Review of risk assessment methodologies Leader: SU (SE), BPI (EL) Participants: UCL (UK), INSA (PT), EAA (AT), EAWAG (CH), TTL (FI), FOEN (CH), INERIS (FR), INSERM (FR), IRFM (IT), ISS (IT), ISSeP (BE), JSI (SI), KI (SE), LSMU (LT), MUI (AT), REGIONH (DK), RSU (LV), SCIENSANO (BE), STAMI (NO), SYKE (FI), UBA (DE), ULUND (SE), VUB (BE), UNIBAS (CH), KEMI (SE) Specific objective of the task for Y1: Initiating case studies reviewing selected methodologies and approaches for regulatory RA  A6.3.1 Substance and effect specific reviews Under the activity, two projects have been initiated: Case studies reviewing substance-specific RA depending on intended use (P6.3.1.a_Y1_SubstanceRA_SU) and Case studies reviewing effect-specific RA (P6.3.1.b_Y1_EffectRA_BPI). Project progress (as described in the AWP Y1 SRIA):  In P6.3.1.a_Y1_SubstanceRA_SU, three reviews (case studies) of substance-specific assessments depending on intended use have been initiated. The case studies have been designed to evaluate and understand differences and similarities, and subsequent implications, across legislations. (SU, UCL, SCIENSANO, IRFM, KI)  P6.3.1.a_Y1_CS12_MethodOSOA_SU: A prioritisation and selection of substances for a case study on risk assessment processes, including significant differences between processes, strengths of the current system(s), and potential gaps, overlaps, or inefficiencies has been initiated.  P6.3.1.a_Y1_CS13_PlasticizersRA_UCL: A mapping of known uses and corresponding legislations for selected plastic additives have been initiated, including comparisons of e.g., testing requirements, use and availability of modelling tools, weight-of-evidence approaches, and derivation of safety thresholds. Peer-reviewed publications are expected to be drafted during the year 2 of PARC. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 50/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1  P6.3.1.a_Y1_CS14_BiocidesRA_SU: A review on the regulation and assessment of biocides when used in cosmetic products compared to biocidal products has been initiated, including how scientific data is used and consequences of the potential differences in regulation and risk assessment.  In P6.3.1.b_Y1_EffectRA_BPI, six reviews of effect-specific assessments have been initiated, including sensitisation and developmental neurotoxicity as well as use of non-animal methods for identification of endocrine disruption, genotoxicity, and carcinogenicity. (REGIONH, STAMI, SU, IRFM, UNIBAS, VUB, ISS, NILU, INSA, BPI, KI, INSERM, INERIS, EAA, UBA)  P6.3.1.b_Y1_CS9_SKINSENSIRISK_REGIONH: A mapping of current practices under different regulations concerning risk assessment of skin sensitizer, including the scientific basis, has been initiated. A questionnaire has been sent to national and EU authorities, industry, and other stakeholders.  P6.3.1.b_Y1_CS10_ED-cosmetics_VUB: A critical analysis of SCCS risk assessments for a selection of the 14 high priority ED cosmetic substances (Group A), including methodology, NAMs, and alternative strategies (NGRA), has been initiated. Contacts with Cosmetics Europe and SCCS.  P6.3.1.b_Y1_CS11_GenotoxCarc_ISS: A mapping of existing documentation, regulations, and related guidelines as well as a review of the methodologies and practices employed under different regulatory frameworks related to genotoxicity and carcinogenicity assessment has been initiated.  P6.3.1.b_Y1_CS15_DNT_SU: An evaluation of conclusions drawn in guideline-compliant developmental neurotoxicity studies has been initiated, with a focus on data availability and data collection, also including if a uniform statistical analysis can identify previously unreported effects.  P6.3.1.b_Y1_CS17_ED-in vitro_BPI: Identification and prioritisation of end-points relevant for the assessment of endocrine disrupting chemicals has been performed. Literature and database search for the identification of available in vitro test methods assessing the prioritised endpoints has been initiated. Interaction with and implementation of results and methods from the EURION cluster.  P6.3.1.b_Y1_CS18_ED-classes_BPI: Identification of available in vitro test methods, in silico models/tools and read-across approaches relevant for the assessment of endocrine disrupting chemicals with regard to androgen, estrogen, steroidogenesis and thyroid modalities has been initiated. Interaction with and implementation of results and methods from the EURION cluster.  A6.3.2 Use of tools, criteria, and methods Under the activity, one project has been initiated: Case studies reviewing tools, criteria, and methods used in regulatory RA (P6.3.2.a_Y1_ToolsRA_SU). Project progress (as described in the AWP Y1 SRIA):  In P6.3.2.a_Y1_ToolsRA_SU, eight reviews on the use of tools, criteria, and methods in regulatory RA have been initiated, including general aspects such as application of risk-based benchmarks and uncertainty analysis as well as aspects related to occupational RA and ERA. (SYKE, ISSeP, SU, STAMI, UBA, JSI, UCL, TTL, KI, RSU, INERIS, MUI, KEMI, ULUND, BPI, LSMU, EAWAG, FOEN) EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 51/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1  P6.3.2.a_Y1_CS1_CARB_SYKE: A survey on risk-based decision benchmarks considered in risk assessment methodologies under different EU regulatory frameworks has been initiated. The scope and methodology have been defined and relevant data compilation is in progress.  P6.3.2.a_Y1_CS2_RiskReduction_SU: A literature review for the identification of available methods on how to evaluate the effectiveness of risk assessment for risk reduction has been initiated.  P6.3.2.a_Y1_CS6_SusChemControl_MUI: The development of a hierarchical mindmap has been initiated with the purpose to identify options beyond AOP, NAM and IATA development for a sustainable regulation of chemicals.  P6.3.2.a_Y1_CS16_UncertaintyRA_ULUND: The description of generic components of uncertainty analyses for common and relevant types of assessment has been initiated. Collection of information on practical challenges through a questionnaire with follow up interviews has been initiated.  P6.3.2.a_Y1_CS7_REGPREP_EAWAG: A review regarding aquatic and sediment RA has been initiated, including identification of substances and mapping of topics for the identification of similarities and differences, and areas requiring further analysis of several different effect values.  P6.3.2.a_Y1_CS4_SecPoisoning_INERIS: A review of current practices applied for secondary poisoning assessment across several regulatory frameworks has been initiated. Particular consideration has been made on the regular review for update of ECHA's chemical safety assessment and reporting tool (Chesar) and European Union System for the Evaluation of Substances (EUSES) under REACH.  P6.3.2.a_Y1_CS8_OccupReproDev_KI: A review of the EU and member state occupational exposure limits for reproductive toxicants 1A or 1B has been initiated. The review includes comparisons of key decisions in the hazard assessments, comparisons to other regulatory areas including REACH.  P6.3.2.a_Y1_CS3_WorkplaceRA_TTL: A review on the existing regulatory documents has been initiated with the purpose to identify case examples on the different options to regulate occupational chemical exposure either under OSH, REACH or both. Joint WP6 workshop A workshop with WP and task leaders, partners, and relevant stakeholders was organised at RIVM, Bilthoven, The Netherlands, on September 15-16, 2022. During day one the WP6 tasks presented their objectives, approaches, and projects. The second day was dedicated to presentations by stakeholders on priorities and regulatory needs as well as guided discussions on how WP6 can contribute to addressing the needs. Presentations were given by DG Sante, DG ENV, JRC, EFSA, ECHA and SCCS. The Coordination team as well as other PARC WPs were represented at the workshop. (KEMI, RIVM, all WP6 partners). List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: Not applicable Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: One case study (12 PMs) planned to be initiated during the period was withdrawn before the start of PARC. This has been communicated to the PARC Coordinator. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 52/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 1.6.4. Task 6.4. Transposing results to regulatory risk assessment methodologies Leader: AGES (AT), UNIBAS (CH) Participants: ANSES (FR), INERIS (FR), OFB (FR), EAA (AT), AGES (AT), MU (CZ), AU (DK), REGIONH-GR (DK), UT (EE), EFSA (EU), SYKE (FI), Tukes (FI), UBA (DE), UFZ (DE), UKOLD (DE), USO (DE), Fraunhofer (DE), UI (IS), ISS (IT), IRFM (IT), LSMU (LT), VUA (NL), NIPH (NO), STAMI (NO), NIVA (NO), NIOM (PL), IEP-NRI (PL), UG-PL (PL), INSA (PT), ENSP (PT), UC (PT), UAVR (PT), ISCIII (ES), UCLM (SI), UGOT (SE), ULUND (SE), RISE (SE), KEMI (SE), SLU (SE), AGROSCOPE (CH), EAWAG (CH), FOEN (CH), UNIBAS (CH), BUL (UK), UKCEH (UK), UOB (UK), BPI (EL) Specific objective of the task for Y1: Laying the groundwork for the development of efficient and protective regulatory RA and underpinning development of regulations through stakeholder workshops, review of knowledge, landscaping exercises, action plan developments and case studies which will inform the decisions on how (and which) approaches should be developed Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A6.4.1. Develop regulatory relevant approaches and methods for chemical mixtures Project progress (as described in the AWP Y1 SRIA):  P6.4.1.a_Y1_CS1_BRUNEL_UGot aims to perform a systematic comparative evaluation of current mixture tools (and those that are currently under development or might be developed within PARC). The mixture tools will be compared regarding their practicability, effectiveness and efficiency, level of protection, feasibility, applications domain and data demands. The first step was to complement the recent literature reviews on the current approaches related to mixtures with information on the current regulatory practices in order to identify the main gaps and needs and possible ways forwards across regulations. Further an overview of the different algorithms for estimating the MAF was made. A survey for collecting data through interviews on current assessment practices and data availabilities is in the initiation phase. A joint discussion with Project leaders of P6.4.1.b_Y1_CS2_UFZ and some partners (EAWAG/ UBA/UKCEH) and a separate discussion with AGES about case studies for further exploring the MAF (useability, size) took place at the WP 6 Workshop in Bilthoven, in the Netherlands on September 15-16 2022 .  In P6.4.1.b_Y1_CS2_UFZ the use of new approach methods (NAMs) i.e., bioanalytical methods for untargeted exposure detection and hazard identification in conjunction with chemical screening data, to deal with unknown mixtures will be compared with mixture risk assessment methods relying on component-based standard toxicity information. Monitoring information based on non-target chemical and bioanalytical methods will be utilised to define unknown mixture exposures. As a first step, a data research and retrieval were performed to build a reference background mixture for European wastewater treatment plant effluents based on monitoring and NAM data including initial data analyses and identification of data gaps. Further, a curation of NORMAN monitoring database for further analyses of compound cooccurrence and mixture heterogeneity across Europe with focus on chemicals regulated under REACH was done. Besides the research, several discussions about this project took place as a EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 53/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 joint discussion and case study identification with UFZ/ EAWAG/ UBA/ UGOT/ UKCEH at the WP6 kick off meeting in Bilthoven. Additionally, the regulatory purpose of the project was discussed on a joint session on mixture regulation by UBA/UFZ (regulators/scientists) at the annual meeting of Topic 9 - One Health of the Helmholtz Program Earth and Environment at UFZ. (AGES, EAWAG, UBA, UFZ, REGIONH, BPI, UI, ISS, LSMU, STAMI, NIVA, IEP-NRI, ENSP, UAVR, KEMI, UGOT, NILZOH, EA, BUL, UKCEH).  A6.4.2. Facilitate the regulatory acceptance and practical use of new methods Project progress (as described in the AWP Y1 SRIA):  P6.4.2.a_Y1_LandscapingSurvey_UNIBAS has conducted several scoping activities in the period June-September 2022, in coordination with WP2 and WP3, as part of its mapping of the status of integration and use of NAMs across the various EU chemical sectors and risk assessment processes. A pilot exercise was conducted combining peer-review & gray literature review with expert consultation to better understand regulatory gaps and needs, and to inform the planning, development, and implementation of a broad expert consultation exercise. In September 2022 we conducted structured interviews with EU risk assessment and chemical safety experts (regulatory and industry) at EU level (Commission and Member States), the UK and Switzerland. This expert elicitation phase informs the development of an online survey to target European chemical risk assessors during the period October-December 2022.  P6.4.2.b_Y1_NGRA_applied in practice_NIPH_VKM started in May 2022 with a planning and scoping phase combining literature review and expert consultation to identify existing tools for evaluating in vitro and in silico studies in a hazard/risk assessment context. To avoid duplicating efforts and create synergies with major US and EU science and regulatory organisations with similar aims and objectives, as well as to recruit specific subject matter expertise in risk assessment and evidence synthesis methods use & tool development, VKM has successfully established an external scientific Advisory Group including 13 participants (Anna Beronius (Karolinska Institutet), Fleur van Broekhuizen (ECHA), Patience Browne (OECD), Ingrid Druwe (U.S. EPA), Thomas Hartung (CAAT, Johns Hopkins), Sebastian Hoffmann (EBTC), Carlijn Hooijmans (Radboud University), George Kass (EFSA), Pilar Prieto-Peraita (JRC), Joshua Robinson (University of California San Francisco), Erwin Roggen (ONTOX), Andrew Rooney (NIEHS), Mathieu Vinken (ONTOX, ASPIS) as well as WP2 and WP3 representatives as observers). Preparatory work for setting the Advisory Group was done in August and September 2022, in close collaboration with WP3, with inputs from WP2 and ANSES. These activities involved drafting a Terms of Reference. The first Advisory group meetings were held in September 2022, which started the work on developing the protocols for evaluation of internal and external validity of in vitro studies. P6.4.2.c_Y1_ML-AI-QSAR_UT started with an exploratory analysis (scoping exercise) for defining the research priorities, incl. target chemical groups and properties, through literature review and consultation with partners (May-August 2022). Due to shared interest with P6.4.2.a_Y1_LandscapingSurvey_UNIBAS, the project is conducted jointly with UNIBAS. Specific inputs were therefore given to UNIBAS to review the literature to support the development of working definitions for artificial intelligence (AI) and machine learning (ML) methods; and develop questions specific to in silico methods to be included in the online survey (August-September 2022). The outcome of the literature review will serve to collect AI&ML-driven QSARs published in the scientific journals and public resources (e.g. source code repositories) (October-December 2022). EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 54/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1  A6.4.3. Developing information transfer structures and enforcement methodology for chemicals in articles to support the transition to a circular economy Project progress (as described in the AWP Y1 SRIA):  P 6.4.3.a_Y1_SuProM_MU will evaluate the currently available information on substances in products and materials and how this information can be integrated in enforcement activities and life cycle assessments, based on a comprehensive review of chemical databases and gap and needs analysis of analytical testing methodologies. In P 6.4.3.a_Y1_SuProM_MU, the initial landscaping exercises were initiated in three key aspects: o 1. Development of a survey distributed to national chemical agencies to gather information on the current use of databases for the implementation and enforcement of chemical regulations, as well as what enforcement activities are done at a regional/national level. This survey was distributed with the support of WP3. This identified agencies that will be active stakeholders in the continuation of P 6.4.3.a. o 2. Mapping of existing (outside of PARC) activities on substances in products and materials, to evaluate the methods used to gather information on substances in products and materials. This was summarised in an internal online workshop in December 2022. o 3. Inventorying of existing databases that can be used to inform on substances in products and materials in conjunction with basic information regarding scope, access, and methods. This was informed from the survey outcomes as well as the internal expertise of the project team.  A6.4.4. Risk assessment to support and promote efficient overall protection of biodiversity Project progress (as described in the AWP Y1 SRIA):  In P6.4.4.a_Y1_CS1_KEMI a series of meetings and workshops have been organised (KEMI, UBA, FOEN). Details on these meetings and workshops including a summary of the minutes will be indicated in the deliverable AD 6.7 (Technical report outlining the regulatory needs for ERA development areas, M24)  The purpose has been to map regulatory needs as expressed in EU Green Deal strategies (e.g. Chemicals strategy / PARC concept paper, Farm to fork and Biodiversity strategy) as well as individual bodies strategies (e.g. EFSA PERA initiative) and transform them into ERA development needs and subsequently into research questions, into identified data gaps and into project deliverables. The meetings and workshops have involved the regulatory core group (KEMI, UBA, FOEN, EFSA and ANSES), project leaders (CKB, UFZ, UKOLD and ISCIII) as well as other partners. An online kick-off meeting involving all partners in 6.4.4 took place on 16 June. A two-half-days physical kick-off workshop involving also all partners in 6.4.4 was held October 6-7 in Berlin. Meetings have also been organised to establish connections to new partners with strategic competence and data resources in ERA and landscape ecology. Work remains to identify and fully integrate available resources among the partners involved in 6.4.4 in terms of data, tools and research competence.  P6.4.4.b_Y1_CS2_SLU aims at exploring ways of simplifying the Predicted Environmental Concentration (PEC) calculations within the Ecological Risk Assessment (ERA). Monitoring datasets and predictive model tools have been identified. Collaboration with WP 4.2 on EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 55/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 gathering monitoring datasets throughout the EU on national and regional level has been initiated. Recruitment of scientific staff has also been done.  P6.4.4.c_Y1_CS3_UFZ aim to develop a protective ERA with reduced complexity and resources required while keeping it as information-rich as necessary. This will be achieved by including only the information and processes that have been proven by ecosystem monitoring and effect modelling to be relevant. Currently, the project is scoping a meta-database which will be used to gather information and data on monitoring of environmental effects that are species related (e.g. ecological and trait based), site related and methods related (e.g. omics data, trait and sensitivity based effect monitoring ).  P6.4.4.d_Y1_CS4_UKOLD aims to ensure that results of any independently performed ERA of a Plant Protection Products (PPP) can be used as a benchmark for ERAs of other PPPs, i.e. comparing and ranking risk profiles of PPPs among substances and in different areas (e.g. for selected organism groups) of the ERA when assessed on the basis of similar level of refinement. This project is still in the scoping and planning phase and the conceptual work has so far been conducted mainly in connection with P6.4.4.a_Y1_CS1_KEMI. Furthermore, data acquisition has begun.  P6.4.4.e_Y1_CS5_ISCIII will develop and explore how landscape-based ERA integrating landscape structures and aggregated (several crops) and combined (several pesticides) exposures can be used to improve the current risk assessment methods. This project is in the conceptualisation phase. The project has started the identification of relevant areas for conducting the case studies and the networking with farmer associations, Integrated Pest Management (IPM) specialists and voluntary initiatives stakeholders to setup the design of each case studies. In parallel, the development of a conceptual model for the use of scenarios in landscape risk assessment has been initiated with a set of brainstorming workshops conducted during 2022. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: Not applicable Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: In general, the activities in the task are delayed by four-six months. The main reason is the short lead time between the approval of PARC application and formal project start, which has given limited time for partners to recruit research staff. There will therefore be a general need to transfer person months from year 1 to year 2 for most projects under 6.4. The project 6.4.2.a_Y1_LandscapingSurvey_UNIBAS has experienced some delays due to intense and sustained administrative and coordination activities with internal PARC partners and external stakeholders, which have significantly slowed down the implementation of planned research activities during the period M1-M6. Several other factors have also contributed to the delays: (i) A number of research projects at EU (and international) level are currently up and running, with very similar aims and objectives to A6.4.2 (how to promote regulatory acceptance of NAMs). This required establishing a fruitful dialogue with a number of organisations outside PARC, as well as with partners across WPs and Tasks, to avoid duplication of efforts and create synergies inside and outside PARC; (ii) because EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 56/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 the Swiss budget was only secured very late, the recruitment process for a new collaborator started late (and is still ongoing). Therefore, AD6.8 “Technical report: mapping exercise assessing the status of integration and use of NAMs across sectorial frameworks” has been postponed to M24, and will be merged with another Additional Deliverable AD.16. This will achieve better coherence, since both deliverables are overlapping, and form two parts of the landscaping exercise. We will report on the outcome of the expert consultation exercise (structured expert interviews, online survey) at the end of Y1. The project P6.4.4.a_Y1_CS1_KEMI has been delayed in terms of contacts and engagement with regulators and policy makers. To avoid duplicate work and promote an efficient use of the time of regulatory agencies and other stakeholders, the dialogue needs to be coordinated with other parts of PARC via WP2 and WP3. Therefore, the Additional deliverable AD6.7 Technical reports outlining the regulatory needs for ERA development areas (M12) has been postponed to month 24. In Y1 this deliverable will be replaced by Draft reports outlining current state of consensus of regulatory needs for ERA development areas. 1.7. Work package 7. FAIR Data 1.7.1. Task 7.1. FAIR Data Policy and implementation 2 Leader: TNO (NL), UOB (UK) Participants: ANSES (FR), BRGM (FR), VITO (BE), MU(CZ), UZIS (CZ), UBA (DE), ISS (IT), KWR (NL), UL-LACDR (NL), UU-IRAS (NL), NIVA (N), UG-PL (PL), JSI (SI), KI (SE), AUTH (EL) Specific objective of the task for Y1: Developing the first version of the PARC FAIR Data Policy (PFDP) and Data Management Plan (DMP), with PARC scientists, stakeholders and the FAIR community, and starting with the implementation of FAIR awareness and skills within PARC Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: General: - Go FAIR Foundation subcontracted to deliver an integrated approach to training in FAIRification according to the three-point FAIRification framework (3PFF) and support in its concrete implementation, and to support the WP in development of conceptual models, vocabularies and ontologies. GFF provides expertise in all relevant FAIR principles, techniques, and technologies, such as persistent unique identifiers, controlled vocabularies, semantic modeling, and ontologies in order to be able to develop FAIR implementation profiles providing machine actionable metadata. - WP7 online kick-off session on May 2022; 2-days physical and online meeting in Brno October 2022, plus numerous task-level and WP-level meetings. Much of the work in WP7 in year 1 was transversal in nature, and significant effort was dedicated to understanding the needs of the other WPs and the first round of projects. Based on these ongoing discussions, WP7-specific projects will be defined during AWPY2 and beyond. 2 The titles of the activities A7.1.1, A7.1.2 and A7.1.3 were not included in the AWPY1 and SRIA. These titles have been added between the submission of the AWP Y1 and the submission of the ASR Y1 and will be added in AWPY2 and its Annex PARC Portfolio project. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 57/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1  A7.1.1 PARC Data Policy and Data Management Plan The following activities were undertaken as part of the development of the initial PARC DMP: - Collection and evaluation of a range of existing DMPs to identify the general and domain-specific best practice. - Outlining of the content of the DMP, and assignment of drafting responsibilities for specific sections. - Facilitation of several discussion and drafting sessions to add content to the initial PARC DMP, identify areas for additional clarification, and build consensus. - Presentation of the initial DMP outline and proposed sign-off process to the PARC MB. - Facilitation of feedback session from WPs / MB on the Initial DMP to ensure it captures all relevant concerns. - Finalisation of the Initial DMP for submission. In parallel, and intensively during the 2-day WP7 meeting in Brno, discussions got underway regarding the content of the PARC Data Policy – an initial Table of Contents (ToC) was prepared and authoring / text drafting responsibilities were assigned, with first drafts of the sections completed by end November 2022, with a further meeting held in early December 2022 to maintain momentum. The ToC was shared with the PARC MB on 10th October, with a request for feedback and any additional suggestions for topics to be covered by the November 7th MB meeting, as the PARC data policy will apply to all PARC partners and thus all should have an opportunity to feed into it. No project submitted at present  A7.1.2 Training and organisation Role descriptions for the Data Champions and Data Liaisons, and the FAIR Implementation Taskgroup (FIT) were developed, and refined based on discussions within WP7 and with the broader PARC team. Once the roles were defined, the process of collecting volunteers for these roles was implemented, with all PARC projects expected to have a data Champion and a Data Liaison, but that each champion and liaison could be responsible for several projects whose activities are clustered based on the type of data they are working with, or the type of challenges they are facing in terms of their data management needs. Training is a core component of the Task 7.1 activities, and has been aligned to the different roles and responsibilities identified as part of the DMP – namely Data Liaisons (from within WP7), data champions (from other WPs / Tasks / projects) and the FAIR Implementation Taskgroup (FIT) who are being trained as trainers to enable them to facilitate further training activities within PARC. The GO FAIR Foundation (GFF) have developed various training activities from FAIR awareness (bottom of the training pyramid as shown in Figure 7.1) up to the Metadata for Machines workshop (M4M) facilitators and trainers. The training to be provided to each of the data champions, data liaisons and FIT experts is shown schematically in Figure 7.1 below. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 64/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022 for the activity 7.3.3: Slightly delayed start. After the dropping out of UU-IRAS, the current co-lead IISPV was leading this activity solo, but now a new co-lead, UoB has been selected and agreed to work on this task. For the scoping study, there is no problem encountered during the implementation of the work planned during this period. However, we may experience common challenges of aligning partners’ expectations in domain-specific case studies as there is still no defined scope in other WPs. We expect it may get more clarified as once other WPs get more organised with their tasks.  A7.3.4 – Identify additional needs in PARC for innovative analyses and promising evolutions in the data science landscape, and translate them in use cases for evaluation The objective of this activity is to identify emerging needs in PARC for innovative analyses on one hand, and promising innovative techniques on the other hand. For this year, we have taken two case studies for the scoping study, which will be further refined and implemented in subsequent years. Activity 7.3.4 has taken a new use case in consultation with WP5 and WP8 and has started working on Activity 7.3.4.a. Pharmacophore modelling using machine learning for screening BBB permeation of xenobiotics. This activity is complementing with data generated in Task 5.1a and the computational tools for the early warning system in Task 8.2. Activity 7.3.4 is collaborating with A6.4.3: AI&ML-driven computational NAMs for use in NGRA lead by UT (EE) and work on Landscaping and readiness of NAMs based on advanced AI&ML approaches for use in chemical RA Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022 for the activity 7.3.4: No problem encountered. List of the deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023 for the task 7.3: Not applicable Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022 for the task 7.3: Described under each activity of the task 7.3 1.8. Work package 8. Concepts and Toolboxes 1.8.1. Task 8.1. Safe and sustainable by design (SSbD) Leader: RIVM (NL), EMPA (CH), AUTH (EL) Participants: INERIS (FR), BNN (AT), MU (CZ), DTU (DK), SYKE (FI), TTL (FI), UBA (DE), ISS (IT), IRFM (IT), IUSS (IT), UNINA (IT), NILU (NO), NMBU (NO), UG-PL (PL), FMUL (PT), NIC (SI), INSST (ES), IVL (SE), BUL (UK), Cefas-Defra (UK) EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 65/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Specific objective of the task for Y1: Increasing the knowledge on methods related to SSbD and providing an inventory of the methods and tools to put SSbD into practice, paving the way towards the operationalisation of the SSbD framework developed by the EC across the various users (industry, regulatory bodies and in academia) Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: Focus has been paid to the development of an efficient communication plan and infrastructure blueprint for an effective science-policy-user interphase, resulting in inclusive dialogue with the EC, users and relevant stakeholders inside and outside PARC, resulting in a collection of first indication on the gaps, barriers, and incentives to gain insight in the completeness, feasibility and applicability of the EC JRC framework has been carried out. For the development of the toolbox, an inventory and review of existing tools that are currently available from existing initiatives on SbD (nano) and SSbD has been carried out. Based on this review, and accounting for the steps identified in the JRC methodology for SSbD assessment, user requirements and functional specifications of the PARC SSbD toolbox are mapped out. In addition, the requirements for use of FAIR data are also explored. In practice, the toolbox is designed to accommodate the translation of the criteria for SSbD and to collate the necessary knowledge along the entire value chain. In this context, an inventory of existing toolboxes and assessment of their applicability will be made to assist in the operationalisation of the SSbD concept in chemical management and innovation. Identification of the most optimal set of parameters for selecting potential use cases to test the methodology developed by the EC and complement the use cases chosen by the EC has also been carried out and based on the discussions so far in Activity 8.1.1 and 8.1.2, a set of potential case studies has been formulated that will allow the testing of the applicability of the EC SSbD criteria and methodology, engaging relevant stakeholders in the value chain, accounting for on the barriers as well as incentives for implementation of different stakeholders that are involved in the use cases. Cooperation with IRISS on value chain interaction is initiated. The development of a systematic approach for knowledge sharing as well as education within PARC and with relevant stakeholders outside PARC (“inception plan”), included the development of an inventory of platforms, initiatives and materials for knowledge and information sharing.  A8.1.1. Translate EC SSbD criteria & methodology towards operationalisation No project submitted at present. In Activity 8.1.1, particular focus has been paid to the development of an efficient communication plan and infrastructure blueprint for an effective science-policy-user interface, resulting in an inclusive dialogue process with the EC, users and relevant stakeholders inside and outside PARC. EU project IRISS is an important partner in addressing the specific needs of the value chains. On top of that, and to keep pace with the state of the art and the lessons learned, a collection of first indications regarding gaps, barriers, and incentives to gain insight in the completeness, feasibility and applicability of the EC JRC framework has been carried out. This was also highlighted in the respective technical kick-off meeting of the activity that took place on 20/09/2022 where the links with the policy developments through contributions from DG RTD, JRC and ECHA were made explicit. To facilitate the process, a communication plan has been coined with the aim to cover: (a) a structured dialogue with the EC; (AUTH, RIVM, DTU) (b) communication inside the PARC consortium (AUTH, RIVM, IVL, DTU, NILU, SYKE, ISS) and outside the PARC consortium (RIVM, AUTH, BNN, IVL, DTU, NILU, INERIS, SYKE, UBA, EMPA, INSST). EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 66/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 The communication plan will be implemented in close collaboration with WP3. In order to review the gaps, incentives and barriers for the practical application of EC framework for SSbD criteria and methodology, the following actions are currently ongoing:  Gathering of lessons learned from best practices focusing on the ‘by-design’(RIVM, AUTH, INSST, ISS, INERIS, TTL, NILU, IUSS, DTU, UBA);  Identification of gaps, barriers, and assessment of completeness, feasibility and applicability of the framework for SSbD criteria by means of focus groups through interviews with all relevant stakeholder groups; in addition, stakeholders will be provided a questionnaire to address these issues comprehensively (IUSS, INSST, TTL, SYKE, RIVM, BNN).  Keeping pace with state of the art (RIVM, TTL, NILU, UBA, AUTH, INERIS). Towards this aim, the SSbD expertise developed within the EU projects RiskGONE and SABYDOMA, and CEFIC-LRI project DOREMI will facilitate the contacts with these projects and the participation to the EC SSbD network. Additionally, a review on risk assessment and management SbD SOPs applicable in early development of nanomaterials is currently ongoing, while this experience will be further explored for broader applications on other chemicals and materials.  A8.1.2. Toolbox development Projects progress (as described in the AWP1 SRIA):  P8.1.2.a_Y1_SSbDToolbox_AUTh For the development of the toolbox, an inventory and review of existing tools that are currently available from existing initiatives on SbD (nano) and SSbD has been carried out. Based on this review, and accounting for the steps identified in the JRC methodology for SSbD assessment, user requirements and functional specifications of the PARC SSbD toolbox are mapped. A list of actions is currently being implemented to aid in this process:  Determination of Gaps and Opportunities (RIVM, UBA, IVL, BUL, UNINA, NILU, TTL)  Priorities for Innovation; Identification of information needs along the innovation process (EMPA, RIVM, ISS, BUL, NILU, UNINA, TTL) In addition, the modalities and need for use of FAIR data is also explored. In practice, the toolbox is designed to accommodate the implementation of the SSbD framework and test its applicability with a view to optimising its practical exploitation. The translation of the framework for Safe and Sustainable by Design (SSbD) chemicals and materials is essential to collate the necessary along the entire value chain. In this context, an inventory of tools in existing toolboxes and assessment of their applicability is being made to assist in the operationalisation of the SSbD concept in chemical management and innovation. In order to operationalise the SSbD framework, existing tools (IVL, IUSS, AUTH, EMPA, NILU, IVL, TTL, RIVM), as well as tools developed within PARC (AUTH, IUSS, RIVM, NILU, IVL, ISS), are being identified and adapted. Furthermore, the conceptual design of the toolbox is being carried out (AUTH, EMPA, IUSS, NILU, BUL, IVL, ISS). Based on this conceptual design, the implementation of the compiled tools into the alpha version of toolbox is currently ongoing (AUTH, IUSS, EMPA, NILU). Towards this aim, existing knowledge gained on toolbox development in other EU SbD and SSbD initiatives is brought in and a direct link with the IRISS project has been established (RIVM, EMPA) to explore the user needs for the toolbox functionalities. The review of existing tools for SSbD assessment has contributed to the determination of gaps and opportunities of the SSbD toolbox regarding data and tool requirements (AUTH). Key input incorporated in the toolbox is also the knowledge and experience on tools for risk and sustainability assessment, as well as the experience of other modelling tools for RA that account for EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 67/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 chemical risk and sustainability assessment such as the INTEGRA LCA (AUTH). At the same time, close collaboration with Task 8.3 has been established, to ensure the proper linkage of the PARC SSbD toolbox within the overall PARC model network (AUTH).  A8.1.3. Towards operationalisation: Use case & indicators In Activity 8.1.3, most of the work carried out so far regards the definition of suitable criteria to select potential use cases to test the methodology developed by the EC and complement the use cases chosen by the EC. Based on the discussions so far in Activity 8.1.1 and 8.1.2 and according to such criteria, a set of potential case studies has been formulated. The following actions are currently underway to facilitate the definition and execution of use cases: • Pilot case study/studies for better common understanding of the SSbD components (IVL) • Establishment of case studies criteria (IVL, UNINA, EMPA, NILU, RIVM) • Finding suitable case studies and organising case studies (IVL) • Operation of case studies; first iteration (IVL) • Summary of learnings and feedback to EC (IVL) • Determination of Gaps and Opportunities (RIVM, UBA, IVL, BUL, UNINA, NILU, TTL) The use cases are defined with a view to allow the testing of the applicability of the EC SSbD criteria and methodology, engage relevant stakeholders along the value chain, consider barriers as well as incentives for implementation relevant to the stakeholders that are involved in the use cases (AUTH). Moreover, an initial inventory of relevant indicators to follow the progresses of sector applicability of the toolbox is made, accounting for initiatives by the EC, including the indicator programme foreseen by EEA and in collaboration with task 3.2 (NILU). Experience on case studies formulation has been brought by several partners work in the domain of nanomaterials and nano-enabled products (RIVM, EMPA).  A8.1.4 Knowledge sharing & Education as key factors for efficient SSbD operationalisation Work carried out in Activity 8.1.4 has been focused on the development of a systematic approach for knowledge sharing as well as education and training within PARC and with relevant stakeholders outside PARC (“inception plan”). This included the development of an inventory on platforms, initiatives and materials for knowledge and information sharing, and education related to SSbD (RIVM, AUTH, UNINA, DTU, IUSS, TTL), the identification of relevant stakeholders and strategies of how to reach them and finally (UBA, RIVM, AUTH, UNINA, IUSS), the connection to WP2 and more specifically to PARCopedia (AUTH) and WP9 and in particular to Task 9.4 training (RIVM, AUTH, UBA, IVL) to develop an approach of how knowledge and education on SSbD can be facilitated within PARC. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays D8.1 Report on the conceptual design of the SSbD toolbox AUTh/EMPA/RIVM 30/04/2023 (M12) Ongoing No significant delay expected EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 68/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.8.2. Task 8.2. Scientific and technical basis for an Early warning system (EWS) on chemical risks Leader: SLU (SE), INSERM (FR) Participants: INRAE (FR), AU (DK), UBA (DE), ISS (IT), IRFM (IT), UniLU (LU), UU-IRAS (NL), VUA (NL), WR (NL), NILU (NO), NMBU (NO), UG-PL (PL), DGS (PT), NIC (SI), IISPV (ES), INSST (ES), ORU (SE), IVL (SE), SLV (SE), UMU (SE), EA (UK), AUTH (EL), EFET (EL), NKUA (EL), UOC (EL) Specific objective of the task for Y1: Developing concepts and protocols for early warning monitoring tools, creating the prioritisation framework Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A8.2.1 EW monitoring tools Projects progress (as described in the AWP1 SRIA):  P8.2.1.a_Y1_EWS_SLU Within T8.2.1, standardised protocols for early warning monitoring tools are currently under development (SLU, INRAE, UniLU, NILU, AU, MTM-ORU, NKUA, UU, VITO, EA), in collaboration with the work done in WP4, with a particular focus on suspect/non-targeted/EDA-based tools for both environmental (SLU, MTM-ORU) and human samples (INRAE, UOC, ISS, VITO). In line with the introduction of NAMs in the RA process, metabolomics-based biomarkers have been defined, together with computational tools that allow their proper interpretation, such as AI methods and advanced bioinformatics algorithms (WFSR, UMU, MTM-ORU, INSERM, UG, AUTH, IRFM, NKUA, UU, IISPV). Towards the aim of information collation, monthly meetings have been organised (SLU). Close collaboration has also been ensured with a dedicated project under task 4.3 (SLU, AU, UU, VITO) to ensure good integration of EWS expectations with regard to innovative screening methods. Moreover, results of monitoring studies (in collaboration with other partners and WP 4) are currently analysed to prioritise substances which are “safe” or with adverse properties, also considering the JANUS software for prioritisation (IFRM). Scoping out metadata terms and suspect lists relevant for this task, along with prioritisation of use data, as well as keywords for scientific and grey literature search for EWS in food safety that are using AI and/or big data analytics (WFSR, UMU, MTM-ORU, INSERM, UG, AUTH, IRFM, NKUA, UU, IISPV) has also been carried out, to search public scientific databases and various EWS systems were identified (AUTH). Main features of the identified systems are now detailed and reported. Also, a literature analysis of existing AI systems in EWS and the summarizing overview in the context of their reliability and usefulness for chemicals prioritisation regarding toxicity is currently ongoing, while an extensive review of the operational EWS from England, namely Prioritisation and Early Warning System (PEWS) for chemicals of emerging concern, has also been completed (EA, AUTH).  A8.2.2: Identification framework EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 69/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 Towards the development of the identification framework in A8.2.2, databases with chemical structure and identifier information have been selected to facilitate the development of computational method for systematic identification and prioritisation of new substances (NKUA, UMU, AUTH). Human biomonitoring samples including available long-term target and non-target screening data from the German environmental specimen bank that are relevant for this task (UBA), and a curated list of currently marketed substances together with other relevant information is collated (UBA). Molecular features which are connected to adverse or critical effects (IRFM, AUTH), from a human toxicological point of view also considering environmental and ecotoxicological aspects are collected, initially characterised by structural alerts (thus local, molecular features) and global parameters (thus properties related to the whole molecule). Metadata terms and suspect lists relevant for this task have been scoping out, along with prioritisation of use data in cooperation with WP7 and WP4 (AU, INERIS, SLV, MTM, NMBU, SLU-IVM, SLU-BVF, NKUA, UBA, EA). Work on the evaluation of existing computational methods and selection of the most promising tools in the context of prioritisation framework is also carried out (UMU, INSERM, AUTH, IRFMN, UG, UniLU, UU), together with a review of scientific articles to recognise main principles and the mechanisms that the system relies on to determine and identify emerging risks (AUTH, SLU). Furthermore, a review of the European institutions libraries (i.e. ECHA, EFSA), grey literature in scientific and public databases (NGO) using keywords for EWS using machine learning to detect hazardous substances in the food safety area has been carried out (INSERM, AUTH). A key work relevant to the identification framework, is the review of the DG ENV Pilot project, that focused on emerging chemical risks to the environment, new substances at research and development stage, new synthetic substances on the market and known or unknown substances that have already been present for some time and for which emerging evidence raises concerns (AUTH).  A8.2.3: Validation of EWS in case-studies Review of existing studies for the identification of possible case studies that can be used for establishment of early warning monitoring tools and prioritisation framework for humans (SLU, AUTH, INRAE, IISPV, UOC, VITO), environment (SLU, MTM, SLV, UOC, EFET, UU), and products (SLU, INRAE, UU) is ongoing; at the moment, two relevant projects, have been identified, (a) one that makes use of long-term non-target screening data in the German riverine environment (UBA) and (b) one in an industrially contaminated area in Greece (AUTH).  A8.2.4: Computational framework to support EWS For the development of the computational framework to support the EWS, a review of existing initiatives has been carried out (AUTH, NKUA, UMU). Given the importance of access to data to feed the EWS, active collaboration with WP7, regarding the FAIR principles to make them accessible for researchers, regulators, policy and other stakeholders (e.g. NORMAN) has been ensured (NKUA, UMU, SLU, UniLU). The evaluation of the available in silico systems and chemical and toxicological screening data for the development of a systematic scoring system to rank and prioritise substances using multicriteria decision analysis is carried out (IRFMN, UG-PL), and the gaps identification will feed the design of the PARC EWS (AUTH). Additional work in A8.2.2 includes the incorporation of a computational framework for screening possible neurotoxins and the prediction of substance transfer across the BBB using AI/ML (IISPV), in line with experimental work and data generated in Task 5.1a. Finally, updates on the NORMAN Suspect List Exchange (NORMAN-SLE) relevant for this task before the end of the year are also introduced, providing feedback on the needs of EWS (NKUA, UMU, MTM, SLU). EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 70/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays AD8.1 Concept and plan of effectbased monitoring of chemicals in the environment SLU/INSERM 30/04/2023 (M12) Ongoing No significant delay expected D8.2 Report on the conceptual design and development guidelines of the PARC EWS SLU/INSERM 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.8.3. Task 8.3. Integrative models Leader: WR (NL), AUTH (EL) Participants: ANSES (FR), INERIS (FR), ISSeP (BE), MU (CZ), DTU (DK), SYKE (FI), TTL (FI), IRFM (IT), IUSS (IT), UL-LACDR (NL), UU-IRAS (NL), WU-TOX (NL), NIVA (NO), NMBU (NO), NIC (SI), IISPV (ES), INSST (ES), UU (SE), UOC (EL) Specific objective of the task for Y1: Deriving the user requirements and the overarching conceptual model for the PARC integrative risk modelling network Summary of the work achieved during the period from 1 May 2022 to 31 December 2022:  A8.3.1: Modelling network, model governance and user requirements For developing a better understanding on the needs of the modelling network, stakeholders have been contacted through an online survey (AUTH, WR. IUSS) and in selected interviews to propose an overview of needs, regulatory user requirements and boundary conditions for relevant RA questions, in addition to the information they receive about existing or planned models (AUTH, WR) across PARC. Task Leaders of 8.3 (AUTH, WR) are also in close collaboration with WPs 3, 4, 5 and 6, receiving input for modelling needs of these WPs and to accommodate their needs in potential case studies. At the moment, the inventory of existing front-end access platforms has been completed (AUTH, WR, DTU, SYKE, IUSS) and a critical review from the user-perspective is carried out (IUSS, UOC). In addition, a case study on bisphenols has been selected as an initial set of use cases (AUTH, IUSS), that comprises a set of compounds both data rich (BPA) and data poor (BPS, BPF and other BPA alternatives).  A8.3.2: Designing and implementing the PARC model network Projects progress (as described in the AWP1 SRIA):  P8.3.2.a_Y1_DIMN_AUTh EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 71/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 The key component of the work foreseen in Task 8.3 for Y1 was the first draft of an overarching conceptual model (AUTH, WR), to map models and platforms to user requirements (AUTH, WR, ANSES, INSERM, IRFM, IISPV) and RA questions (WR, ANSES, INSERM). In this direction, the conceptual PARC model has been designed (AUTH, WR) as an open-source dynamical system under version control, to allow continuous development and adaptation to regulatory needs to create web service connections between models and platforms in the area of chemical RA, covering the whole source to effect and impacts continuum. In the Task 8.3 kick-off meeting, held virtually on 26/09/2022, all partners had the opportunity to present models such as MCRA, INTEGRA, USEtox, VEGAHUB, ConsExpo, PACEM, (AUTH, WR, ANSES, INSERM, INERIS, ISSeP, DTU, SYKE, IRFM, IUSS, ULLACDR, UU-IRAS, NIVA, IISPV, INSST, UU, UOC) which facilitated the process for the preparation to connect them in the PARC model network. Uncertainty issues across the overall chain of calculations have been discussed as well (MU, IISPV, WR, AUTH), in close collaboration with Task 7.3. Six focus groups have been proposed (integrated platforms and cross cutting issues (AUTH, WR, DTU, UU, IISPV, VITO), QSAR models (IRFM, UT), PBK models (INERIS, AUTH, IISPV, IUSS, ANSES, WR), hazard models (IRFM, UL-LACDR, AUTH, WR), and application in case studies (NIC, NIVA, NMBU, VITO, VUA, WU-TOX) to organise practical collaborations for the PARC model network. Task 8.3 is also member of the cross-WP group on development of a PARC ontology (WR, IISPV, AUTH, VITO), to support FAIR data sharing and model integration within the PARC model network. With regard to individual model development to be included in the model network: - Initial links between the MCRA model (WR) and tools for HBM data (VITO) analysis were established, to support the research activities in the real-life mixtures project (6.2.3). In addition, multivariate statistical methods for real-life mixture selection from HBM data were implemented in MCRA, and functionality to link PBK models (INERIS) to MCRA was developed. - The developers of INTEGRA (AUTH) are working on the link of internal dose estimates of parent compounds and metabolites with system biology models (UOC, IUSS), towards systems biology based AOPs (INSERM). In order to render INTEGRA interoperable with the rest of the model network, modifications will be done in the direction of following the common inputoutputs formats (entry points) that will be commonly decided in T8.3 for the PARC model network, including necessary modules for adapting to the required spatial and temporal scale(s). - The UNEP/SETAC global scientific consensus model USEtox (https://usetox.org) was adapted to include risk screening metrics applicable for use in European chemical RA (DTU), while being fully consistent with mass balance-based approaches used in Life Cycle Assessment (LCA) assessment as e.g. implemented in the European Product Environmental Footprint (PEF) and SSbD frameworks, both coordinated by JRC. The adaptations under PARC ASRY1 cover both chemical emissions along product and technology life cycles as well as chemicals in product and process applications, and are internal contributions to PARC from the USEtox International Centre. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays AD8.2 First draft conceptual model describing models in the modular network and their connections WR/AUTH 30/04/2023 (M12) Ongoing No significant delay expected EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 72/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 D8.3 Report on the conceptual design of the integrative tools WR/AUTH 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered.  A8.3.3 Application of the integrative model network in use cases This activity has not started during the Y1 of PARC. 1.9. Work package 9. Building Infrastructural and human capacities 1.9.1. Task 9.1. Laboratory networking Leader: ISCIII Participants: ANSES, INERIS, Oniris, BRGM, LNE, ISSeP, Sciensano, MU, VSCHT, AU, IPA, RSU, NPHSL, LNS, NIPH, STAMI, NMBU, FMUL, INSA, SZU-SK, UK, CSIC, FISABIO, FNS, BPI, GCSL Specific objective of the task for Y1: i) Establishing the network of WP9 partners, contact points from other Work Packages (WPs), and expert groups, ii) identifying priority infrastructural needs through consultations with WPs 2-8, ii) finding consensus on the overall architecture of information catalogues, iii) landscaping and developing pilot information catalogues and networks for laboratories Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: The network of task 9.1 partners has been established. Consultations with other WPs on the laboratory networking needs and priority areas are performed on an ongoing basis supported by contact points, especially with WP4, on human biomonitoring and environmental monitoring. The structure and characteristics of catalogues are being defined in collaboration with WP7 and several meetings were held for this purpose in Oct/Nov 2022, in the frame of Task 9.1 and 9.2. The collection of information from laboratories in the field of human biomonitoring has been initiated in close collaboration and coordination with Task 4.1 (in particular activity 4.1.2), and the initial catalogue will be available by M12 (ISCIII has led the activity with the contribution from ANSES, LNE, ISSeP, Sciensano, MU, VSCHT, AU, IPA, NPHSL, LNS, NIPH, STAMI, NMBU, FMUL, INSA, SZU-SK, UK, CSIC, FISABIO, FNS, BPI, GCSL). Regarding the creation of air, indoor or consumer products laboratory catalogues, partners with expertise in these fields have been identified through consultation. ISCIII and MU led this activity, with contribution from Task 9.1 and 9.2 partners. Survey formatting, distribution, and collection were discussed and aligned with WP2 and WP3 (Oct/Nov 2022). A self-administered online survey was developed to gather information on laboratory availability and capacities in the different fields. One specific survey for HBM was distributed in collaboration with activity 4.1.2 among PARC partners and beyond, to detect laboratories interested in being a member of the network. Another survey, including information about biomarkers and analytical capacities will be launched at the beginning of 2023. Regarding laboratories on air, indoor and articles (consumer products), planned by Y1, other surveys will be developed early in 2023, to detect laboratories with expertise in these fields and their capacities. Data collected in the surveys will be analysed/compiled in the specific catalogues. EUROPEAN PARTNERSHIP This partnership has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 73/77 PARC — HORIZON-HLTH-2021-ENVHLTH-03 Contract No. 101057014 D1.4 ASRY1 The collection of information from partners and laboratories depends on the availability and dissemination of surveys. The interdependency of activities in PARC in general and in this activity in particular with WP2 and WP3, to define the format and distribution in a coordinated way, might delay the information collection and thereby the initial catalogues. T9.1 has been working mainly in A9.1.1 over these 8 months of PARC, to create the initial catalogues of laboratories. A9.1.2 and 9.1.3 as described in the AWPY1 SRIA will be in charge of develop networking activities to secure the coordination and activity of the networks and the development of the less developed networks. These will be done over the next years, once the networks and members had been identified. A9.1.4 will define the design of the laboratory dashboard, to be done in 2023. List of deliverables, additional deliverables and milestones to be achieved during the period from 1 May 2022 to 30 April 2023: No. Title Leader Due date Actual Delivery date Explanation related to delays D9.1 Initial laboratory catalogue and design of the network platform (dashboard) Y1 ISCIII 30/04/2023 (M12) Ongoing No significant delay expected Problems encountered during the implementation of the work planned during the period from 1 May 2022 to 31 December 2022, if any: No problem encountered. 1.9.2. Task 9.2. Building exposure monitoring capacities Leader: MU Participants: ANSES, Inserm, Oniris, LNE, SpF, ISSeP, Sciensano, IMROH, AU, NPHC, NPHSL, LNS, UU-IRAS, STAMI, FMUL, INSA, ENSP, SZU-SK, CSIC, ISCIII, AUTH, BPI, GCSL Specific objective of the task for Y1: Establishing the network of WP9 partners, contact points from other WPs, and expert groups, ii) identifying priority infrastructural needs through consultations with WPs 2-8, ii) finding consensus on the overall architecture of information catalogues, iii) landscaping and developing pilot information catalogues and networks for exposure monitoring networks. Summary of the work achieved during the period from 1 May 2022 to 31 December 2022: Task 9.2 partners (MU) has led the activity with the contribution from ANSES, AU, AUTH, GCSL, INSERM, NPHHC, RIVM, SpF, and UU-IRAS) contributed to the mapping and discussion of the existing platforms and systems potentially suitable for building the catalogues of environmental and biomonitoring networks. Possible solutions were presented to partners in WP9 and WP7 (Oct-Nov 2022), due to the need to take into account FAIR aspects already in the initial phase of catalogue building, and summarised in a report (Oct/Nov 2022). In addition, the development of catalogues on air monitoring (in cooperation with 4.2) and Human Biomonitoring/population studies/networks (in collaboration with 4.1) and on networks related to articles/indoors (in cooperation with 6.4.3), including the available sample and data collections in support of their further use in WPs 4-8, was initiated, where the initial inventories will be available by M12 (AU (domains: air, articles, indoor), CSIC (domain: air), ISCIII (domain: HBM), ISSeP (domains: