PROGRAMME Workshop on critical innovations in pesticides safety testing and chemical risk assessment for developmental neurotoxicity (DNT)
28-30 October 2024
Programme
OECD Workshop on Critical Innovations in pesticides safety testing and chemical risk assessment, for developmental neurotoxicity DNT
Day 1 – 28 October 2024
Theme: Leverage on available experience from applying DNT-In vitro Battery (IVB) data
9h00
Welcome by the OECD
9h15
Patience Browne and Anne Gourmelon, OECD Environment Directorate
Welcome by the CRP and introduction to the Programme
Lieve Herman, CPR Scientific Advisory Body
Session 1: Lessons learned from existing IATA case studies using DNT-IVB data
Chairs: Iris Mangas, European Food Safety Authority (EFSA), Italy and Tim Shafer, United States Environmental Protection Agency (US EPA), United States
Build off previous OECD IATA Case Studies on DNT and the Initial Recommendations on Evaluation of Data from the DNT-IVB published in 2022 and 2023, respectively. These efforts identified the need to elaborate on what was learned so far and identify the focus of additional efforts to accelerate the uptake of DNT-IVB for regulatory purposes. The ultimate goal of the first theme is to take a step forward from those efforts and discuss specific solutions to specific issues that were raised from the case studies to address different regulatory problem formulations (e.g., IVIVE, AOPs, in vivo and in vitro uncertainties, applicability domain, molecular characterisation, etc.).
09h30
US Division of Translational Toxicology (DTT): IATA case study for DNT to prioritise a class of chemicals
Helena Hogberg, NICEATM, US Division of Translational Toxicology (DTT), NIEHS, United States (presentation: 20min; technical Q&A: 5min)
09h55
Case studies from large European (Horizon 2020) projects to refine testing strategies
Marcel Leist, University of Konstanz, CAAT-Europe, Germany (presentation: 20min; technical Q&A: 5min)
10h20
US EPA Case-studies: Prioritisation, Weight of Evidence and Waiving in vivo DNT test studies
Tim Shafer, United States Environmental Protection Agency (US EPA), United States
3 (presentation: 20min; technical Q&A: 5min)
Tea/Coffee Break (10h45-11h15)
11h15
EFSA’s IATA Case Studies for hazard identification and characterisation lessons learnt
Iris Mangas, European Food Safety Authority (EFSA), Italy (presentation: 20min; technical Q&A: 5min)
11h40
Industry perspective on leveraging the mechanistic understanding from the DNT-IVB to optimise the development of safe pesticides
Agnes Karmaus, Syngenta, United States (presentation: 20min; technical Q&A: 5min)
12h05
Inclusion of the DNT-IVB in EU’s Pesticides Risk Assessment – a European Member State Perspective
Verena Haudek-Prinz, Austrian Agency for Health and Food Safety, Austria (presentation: 20min; technical Q&A: 5min)
Lunch break (12h30-13h30)
13h30
IATA for chemical classification: special considerations when using DNT-IVB data
Martin Paparella, University of Innsbruck, Austria (presentation: 20min; technical Q&A: 5min)
13h55
DNT-IVB data application for screening chemicals: industry’s perspective
Sue Marty, Dow Chemicals, United States (presentation: 20min; technical Q&A: 5min)
Session 2: Exposure assessment and Quantitative In vitro to in vivo extrapolation (QIVIVE)
Chairs: Cecilia Tan, United States Environmental Protection Agency (US EPA), United States, US and Jochem Louisse, European Food Safety Authority (EFSA), Italy
In risk assessment, tiered testing is a stepwise approach that combines existing information on both exposure and hazard with the goal of obtaining uncertainty levels acceptable to the regulatory need on both. Positive activity in one or more assays in the DNT-IVB should be coupled with existing exposure information and adequate uncertainty analysis to determine whether the data is acceptable for the regulatory need. The need to perform PBK modellingfacilitated QIVIVE of DNT-IVB data has been highlighted in the IATAs published with hazard characterisation or risk assessment problem formulations. Further work and a road map are needed to develop a tiered exposure modelling framework that will allow the use of the DNT-IVB in vitro bioactivities to derive a PoD (Point of Departure) for human health risk assessment.
14h20
Towards quantitative in vitro to in vivo extrapolation of DNT IVB data: principles and considerations for regulatory application
Jochem Louisse, European Food Safety Authority (EFSA), Italy (presentation: 20min; technical Q&A: 5min)
14h45
Maternal exposure and development neurotoxicity effects in offsprings: tiered modelling approaches
Cecilia Tan, United States Environmental Protection Agency (US EPA), United States (presentation: 20min; technical Q&A: 5min)
Tea/Coffee break (15h15-15h45)
15h45
Deltamethrin - PBK/IVIVE strategy to consider developmental neurotoxicity (DNT) in vitro data for human health risk assessment
Katrin Bothe and Dennis Mueller, Bayer, Germany (presentation: 20min; technical Q&A: 5min)
16h10
QIVIVE in developmental neurotoxicity: The role of in vitro distribution kinetics
Nynke Kramer, Wageningen University, The Netherlands (presentation: 20min; technical Q&A: 5min)
16h35
Panel Discussion of Sessions 1 and 2
Prioritisation of Future Efforts: Identification of common strengths and limitations of the approaches used among the various case studies. Aims to decide on the selection of strengths that can be standardised/reused and to identify current limitations (i.e., technical, lack of data, lack of specific guidance, etc.) that need development efforts. Within those limitations, identify those that must be solved to use the DNT-IVB data as PoD and those that would be nice to decrease the uncertainty when doing so and summarise future research or regulatory goals for each of them.
Moderator: Patience Browne, OECD Environment Directorate
17h30 END OF DAY 1
Day 2 – 29 October 2024
Theme: Regulatory implementation of the DNT-IVB
09h00
Break-out group discussion on case studies, guided by charge questions. What can be a short-medium term plan for the use of the DNT-IVB for:
1. Use of DNT-IVB data as complementary information as part of the WoE in an IATA
2. Moving forward to an agreed tiered testing strategy
3. DNT Defined approach development
Breakout (BO) group Topic
BO group 1 Use the DNT-IVB data as complementary information and part of the WoE in an IATA. What are the next steps for standardisation?
BO group 2 Moving forward to an agreed-tiered testing strategy. What is still missing?
BO group 3 Defined approach/es development for DNT testing. Are we there yet?
Tea/Coffee Break (during the BO session)
Moderators
Moderators: Iris Mangas & Jochem Louisse
Moderators: Josh Harrill & Ellen Fritsche
Moderators: Helena Hogberg & Agnes Karmaus
Theme: Tiered testing strategy for application of DNT-IVB
Session 3: Tiered testing, Additional Assays and Non-Mammalian Animal Models– What do they have to offer to the DNT-IVB?
Chair: Ellen Hessel, RIVM, The Netherlands
The third session will focus on strategies for tiered testing, improvements to the current DNT-IVB, and non-mammalian models for DNT. It will be an opportunity to identify any knowledge gained from CROs’ or researchers’ experience with additional assays to cover neurodevelopmental processes not represented in the DNT-IVB and non-mammalian animal models. It will also highlight any areas of research that will inform revisions to Initial Recommendations 11h30
The EFSA DNT-RAP project - Laboratory transferability and accessibility of the DNT-IVB test methods
Katharina Koch, IUF – Leibniz Research Institute for Environmental Medicine, DNTOX, Germany (presentation: 25min; technical Q&A: 5min)
Lunch break (12h00-13h30)
13h30
Transfer of, data generation from, and comparison to existing data from the developmental neurotoxicity in vitro battery
Megan Culbreth, Human Foods Program, U.S. Food and Drug Administration (FDA), United States (presentation: 25min; technical Q&A: 5min)
14h00
Tiered testing and considerations for integrating additional assays and models to the DNT-IVB
Ellen Fritsche, SCAHT - Swiss Centre for Applied Human Toxicology, Switzerland (presentation: 25min; technical Q&A: 5min)
14h30
High-throughput Phenotypic Profiling with Cell Painting as a potential first-tier DNT Screen
Joshua Harrill, Center for Computational Toxicology and Exposure (CCTE), United States Environmental Protection Agency (US EPA), United States (presentation: 25min; technical Q&A: 5min)
15h00
3D human stem cell-derived models for developmental neurotoxicity studies
Lena Smirnova, Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, United States (presentation: 25min; technical Q&A: 5min)
Tea/Coffee break (15h30-16h00)
16h00
The added value of non-mammalian animal models to fill the gaps in developmental neurotoxicity
Lee Ellis, National Research Council of Canada, Canada (presentation: 25min; technical Q&A: 5min)
16h30
Panel Discussion of Session 3
Future directions: The ultimate goal of this discussion is to develop a roadmap through which improvements to the Initial Recommendations can be made. Specifically, i) identify the status of assay transfers and determine what additional efforts are needed, if any, ii) begin to define more clearly tiered testing approaches to DNT and how to implement them, and iii) understand the value of alternative species and how they fit into the current DNT-IVB.
Moderator: Tim Shafer, United States Environmental Protection Agency (US EPA), United States
17h30 END OF DAY 1
Day 3 – 30 October 2024
Session 3: Tiered testing, Additional Assays and Non-Mammalian Animal Models– What do they have to offer to the DNT-IVB? (Cont.)
09h00
Plenary feedback from breakout groups and discussion
Moderators from breakout groups: Iris Mangas European Food Safety Authority (EFSA), Italy, Josh Harrill United States Environmental Protection Agency (US EPA), United States and Helena Hogberg NICEATM, US Division of Translational Toxicology (DTT), NIEHS, United States
10h00
Developing new assays to predict glia-related KNDPs with transcriptomics data support Oddvar Myhre, Norwegian Institute of Public Health, Norway (presentation: 25min; technical Q&A: 5min)
10h30
Microglia for Studying Developmental Neurotoxicity
Kelly Carstens, United States Environmental Protection Agency (US EPA) (presentation: 25min; technical Q&A: 5min)
Tea/Coffee Break (11h00-11h30)
11h30
Evaluation of neurotoxicity for pesticide-related compounds in human iPS cell-derived neurons using microelectrode array: Japanese experience
Yasunari Kanda, Division of Pharmacology, National Institute of Health Sciences, Japan (presentation: 25min; technical Q&A: 5min)
Theme: Develop Action Plans to Implement Recommendations
12h00
Open Discussion-Workshop Results and Next Steps
Participants are invited to reflect on the presentations and discussions of the last two days and contribute to this agenda item to shape the recommendations, outcomes, and action plans for 1) Updating the Initial Recommendations to include transferability, 2) Efforts to develop tiered testing, and 3) Efforts to develop an IATA framework template and move gradually to defined approach(es) for DNT.
Moderators: Iris Mangas, European Food Safety Authority (EFSA), Italy, Tim Shafer, United States Environmental Protection Agency (US EPA), United States and Helena Hogberg, NICEATM, US Division of Translational Toxicology (DTT), NIEHS, United States, United States
12h45
Wrap-Up and Leaving Address by the CRP
13h00
Conference closes
Herman, CPR Scientific Advisory Body
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