HESI Workshop
Quantitative Interpretation of Genetic Toxicity Dose-response Data for Risk Assessment and Regulatory Decision-making – State of the Science, Applications, and Persistent Challenges
Andreas Zeller (Roche), George Johnson (Swansea University), Paul White (Health Canada)
on behalf of the HESI GTTC
| HESI Workshop | Monday 15th May: 9:00 - 15:00 (Forum 2) |
|---|---|
| 8:00 - 9:00 | Registration & Breakfast |
| Quantitative Dose-response Analyses: State of the Science | |
| 9:00 - 9:10 | Welcome & Overview of Workshop Goals Co-chairs: Andreas Zeller (Roche, SWITZERLAND), George Johnson (Swansea University, UK), Paul White (Health Canada, CANADA) |
| 9:10 - 9:40 | Quantitative Interpretation of In Vivo Mutagenicity Dose Response Data for Risk Assessment and Regulatory Decision-Making Paul White (Health Canada, CANADA) & Stefan Pfuhler (Procter and Gamble, USA) |
| 9:40 - 10:10 | The interpretation of in vitro dose-response data for risk assessment and regulatory decision-making Marc Beal (Health Canada, CANADA) |
| 10:10 - 10:40 | Guided Discussion |
| 10:40 - 11:10 | Coffee Break |
| Application of Quantitative Data Interpretation to Pharmaceutical Impurities | |
| 11:10 - 11:40 | Nitrosamine impurity issues and potential resolutions George Johnson (Swansea University, UK) |
| 11:40 - 12:10 | In vivo genetic toxicity assessments for nitrosamines Maik Schuler (Pfizer, USA) or Shaofei Zhang (Pfizer, USA) |
| 12:10 - 12:40 | Defining a NOGEL for mutation induction in Muta™Mouse following exposure to N-Nitrosodimethylamine (NDMA) Anthony Lynch (GlaxoSmithKline, UK) |
| 12:40 - 13:40 | Lunch |
| 13:40 - 14:10 | Regulatory considerations related to mutagenic impurities in pharmaceuticals Roland Frotschl (BfArM, GERMANY) |
| 14:10 - 14:50 | Guided Discussion |
| 14:50 - 15:00 | Concluding Remarks |
15:00 – 15:30
REGISTRATION
15:30 – 16:00
Open Ceremony
16:00 – 17:00
RNA-mediated genome instability and transcription-replication conflicts
Andrés Aguilera (Keynote Speaker)
(University of Seville, SPAIN)
| Session 01: EEMGS New Investigators (EEMGS NI) | Monday 15th May 17:00 - 18:30 (Forum 2) | Chairs: Fiona Chapman (Imperial Brands, UK) & Julen Sanz (Vrije Universiteit Brussel, BELGIUM) |
|---|---|---|
| 17:00 - 17:30 | Helena Reinardy (Invited Speaker) (Scottish Association for Marine Science) UK A journey in pursuit of marine genetic toxicology |
|
| 17:30 - 17:45 | Julie Sanders (Sciensano) BELGIUM Mixtures of genotoxicants: does the principle of additivity applies? |
|
| 17:45 - 18:00 | Axel Rosendahl Huber (IRB Barcelona) SPAIN Estimating the mutation risks conferred by mutational processes |
|
| 18:00 - 18:15 | Demi Pritchard (Swansea University) UK Negative data is still useful data: investigating and detecting non-genotoxic carcinogens in vitro |
|
| 18:15 - 18:30 | Alba García-Rodríguez (Autonomous University of Barcelona) SPAIN Modeling human-derived in vitro barriers for environmental toxicology |
El Merendero de Antonio Martín
Pl. de la Malagueta, 4, 29016 Málaga
| Session 02: International Workshops on Genotoxicity Testing (IWGT) | Tuesday 16th May 9:00 - 11:00 (Forum 1) | Chairs: Andreas Zeller (Roche, SWITZERLAND) & Hans-Joerg Martus (Novartis, SWITZERLAND) |
|---|---|---|
| 9:00 - 9:30 | Mirjam Luijten (Invited Speaker) (National Institute for Public Health and the Environment) THE NETHERLANDS Evaluation of the Standard Battery of In Vitro Genotoxicity Tests for Human Health Risk Assessment through Mathematical Modelling: A Report of the International Workshop on Genotoxicity Testing (IWGT) |
|
| 9:30 - 10:00 | Carol Beevers (Corteva Agriscience) UK In Vivo Genotoxicity Testing Strategies: Report of the International Workshop on Genotoxicity Testing (IWGT) |
|
| 10:00 - 10:30 | Stephen Dertinger (Litron Laboratories) USA Assessing the Quality and Making Appropriate Use of Historical Negative Control Data: A Report of the International Workshop on Genotoxicity Testing (IWGT) |
|
| 10:30 - 11:00 | Hans-Joerg Martus (Novartis) SWITZERLAND Summary of 8th IWGT in Ottawa, Canada |
| Session 03: New Approach Methodologies (NAMs) | Tuesday 16th May 9:00 - 11:00 (Forum 2) | Chairs: Guillermo Repetto (Universidad Pablo de Olavide de Sevilla, SPAIN) & Isabel Gaivão (Universidade de Trás-os-Montes e Alto Douro, PORTUGAL) |
|---|---|---|
| 9:00 - 9:45 | Francesca Caloni (Invited Speaker) (University of Milan) ITALY 3Rs: from complexity to predictivity |
|
| 9:45 - 10:00 | Ludovic Le Hégarat (French Agency for Food, Environmental and Occupational Health & Safety - Fougeres Laboratory, Toxicology of Contaminants Unit) FRANCE The human HepaRG cell line: a brief history of its use in genetic toxicology: advantages, limits and future directions |
|
| 10:00 - 10:15 | Julia Catalán (Finnish Institute of Occupational Health) FINLAND In vitro cell transforming capacity of different types of nano-plastics |
|
| 10:15 - 10:30 | Elsje Burgers (Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research - Leiden University) THE NETHERLANDS In silico modelling of crosstalk between DNA damage and oxidative stress for prediction of cellular adversity |
|
| 10:30 - 10:45 | Lieselot Hemeryck (Laboratory of Integrative Metabolomics, Ghent University) BELGIUM Perspectives for DNA adductomics in large-scale exposomics: upscaling sample preparation and preprocessing data |
|
| 10:45 - 11:00 | Ann-Karin Olsen (Norwegian Institute of Public Health, Division of Climate and Environmental Health) NORWAY Oxidative Stress Disrupt Differentiation of Human Induced Pluripotent Stem Cells |
11:00 – 11:30
Coffee Break
| Session 04: International Comet Assay Working Group (ICAWG) | Tuesday 16th May 11:30 - 13:00 (Forum 1) | Chairs: Goran Gajski (Institute for Medical Research and Occupational Health, CROATIA) & Amaya Azqueta (Universidad de Navarra, SPAIN) |
|---|---|---|
| 11:30 - 12:00 | Bojana Žegura (Invited Speaker) (Department of Genetic Toxicology and Cancer Biology, National Institute of Biology) SLOVENIA Advanced 3D cell models and zebrafish embryos: A bridge between in vitro and in vivo |
|
| 12:00 - 12:15 | Mugimane Manjanatha (Division of Genetic and Molecular Toxicology, US FDA, National Center for Toxicological Research) USA Utility of 3D HepaRG spheroid model for testing genotoxicity using high-throughput CometChip platform |
|
| 12:15 - 12:30 | Miguel Collía (Department of Pharmacology and Toxicology, School of Pharmacy and Nutrition, Universidad de Navarra) SPAIN Use of the CometChip® for the in vitro, in vivo and Fpg-modifed assay |
|
| 12:30 - 12:45 | Lada Zivkovic (Department of Pathobiology, Faculty of Pharmacy, University of Belgrade) SERBIA Evaluation of antioxidative, antigenotoxic, and anticancer activities of commercial medical mushrooms products: Agaricus blazei, Cordyceps Sinensis and Immune Assist |
|
| 12:45 - 13:00 | Vanessa Andrade (Laboratory of Translational Biomedicine, Graduate Program of Health Sciences, University of Southern Santa Catarina – UNESC) BRAZIL Maternal exercise during pregnancy modulates genetic and biochemical damage caused by high consumption of fructose in offspring |
| Session 05: Ecotoxicology | Tuesday 16th May 11:30 - 13:00 (Forum 2) | Chairs: Awadhesh Jha (University of Plymouth, UK) & Óscar Herrero (Universidad Nacional de Educación a Distancia, SPAIN) |
|---|---|---|
| 11:30 - 12:15 | Marinella Farré (Invited Speaker) (Institute of Environmental Assessment and Water Research) SPAIN The challenge of assessing contaminants of emerging concern and microplastics |
|
| 12:15 - 12:30 | Awadhesh N. Jha (School of Biological and Marine Sciences, University of Plymouth) UK Assessing the Impact of Persistent and Emerging Contaminants on Aquatic Organisms |
|
| 12:30 - 12:45 | Fengjia Liu (The Scottish Association for Marine Science) UK Hydrogen peroxide-induced oxidative damage in sea urchin (Paracentrotus lividus) DNA |
|
| 12:45 - 13:00 | Mujo Hasanović (University of Sarajevo - Institute for Genetic Engineering and Biotechnology) BOSNIA & HERZEGOVINA Plant comet assay in biomonitoring of air pollution in Sarajevo, Bosnia and Herzegovina |
13:00 – 14:00
Lunch
| Pitch-poster Presentation 1 | Tuesday 16th May 14:00 - 14:30 (Forum 2) | |
|---|---|---|
| 14:00 - 14:05 | Carina Ladeira (Health & Technology Research Center, Escola Superior de Tecnologia da Saúde) PORTUGAL Blood molecular profile to predict genotoxicity from exposure to antineoplastic drugs – a comparison with cytokinesis-block micronucleus assay results |
|
| 14:05 - 14:10 | Alonso Rodríguez Pescador (University of Oviedo) SPAIN Internalization, toxicity, and genotoxicity of ultra-small non-magnetic iron oxide (III) nanoparticles in cultured cell lines and Drosophila larvae in vivo |
|
| 14:10 - 14:15 | Michaela Blažíčková (Biomedical Research Center) SLOVAKIA Determination of proliferation and genotoxic effect of thymol and acetyl thymol on in vitro intestinal model |
|
| 14:15 - 14:20 | Sharleen Friese (DUniversity of Potsdam) GERMANY Variations of Dietary Trace Element Supply and its Consequences on Genomic Stability in the Murine Cerebellum |
|
| 14:20 - 14:25 | Aliro Villacorta (Universidad Arturo Prat) CHILE A new source of representative secondary PET nanoplastics. Obtention, characterization, and hazard evaluation |
|
| 14:25 - 14:30 | Anastasiya Mircheva (Department of Pharmacology and Toxicology, Maastricht University) THE NETHERLANDS Investigation of base excision repair and oxidative stress in preeclampsia-complicated placentas – a pilot study |
14:30 – 16:00
Poster Session 1 & Sponsor Visit
(while coffee is served)
16:00 – 17:00
Chromosome instability, DNA repair deficiency and cancer: insights from Fanconi anemia
Jordi Surrallés (Keynote Speaker)
(Santa Creu i Sant Pau Hospital Research Institute Foundation, SPAIN)
18:30 – 20:30
Social Event
Plaza de la Merced
(meeting point)
| Session 06: ECETOC | Wednesday 17th May 9:00 - 11:00 (Forum 1) | Chairs: Roland Frötschl (BfArM, GERMANY) & Bennard van Ravenzwaay (Environmental Sciences Consulting, GERMANY) |
|---|---|---|
| 9:00 - 9:15 | Bennard van Ravenzwaay (Invited Speaker) (Environmental Sciences Consulting) GERMANY An Introduction to ECETOC’s workshops on Point of Departure and IVIVE modelling |
|
| 9:15 - 9:40 | Stephan Schaller (esqLABS) GERMANY Physiologically Based Kinetic Modelling applications in Chemical Risk Assessment |
|
| 9:40 - 10:05 | Richard Currie (Syngenta International Research Center) UK Applying transcriptomic benchmark modelling for toxicological decision making |
|
| 10:05 - 10:30 | Franziska Zickgraf (BASF) GERMANY Determination of point of departures based on high throughput in vitro metabolomics |
|
| 10:30 - 10:50 | Tim Gant (UK Health Security Agency) UK Summary of the ECETOC workshop from IVIVE to PODS – translating research methods to application |
|
| 10:50 - 11:00 | General Discussion |
| Session 07: DNA Repair, Chromatin Structure and Genome Stability | Wednesday 17th May 9:00 - 11:00 (Forum 2) | Chairs: María Teresa Roldán (Universidad de Córdoba, SPAIN) & Luisa María Sierra (Universidad de Oviedo, SPAIN) |
|---|---|---|
| 9:00 - 9:45 | Haico van Attikum (Invited Speaker) (Leiden University Medical Center) THE NETHERLANDS Specific killing of BRCA1-deficient cancer cells by depletion of EXO1 |
|
| 9:45 - 10:00 | Marina Jordano Raya (University of Córdoba) SPAIN Influence of orphan base and sequence context on the processing of AP sites by AP lyases in Arabidopsis thaliana |
|
| 10:00 - 10:15 | Helga Stopper (Institute of Pharmacology and Toxicology, University of Wuerzburg) GERMANY Role of Phosphatase and Tensin homolog (Pten) in Insulin mediated DNA damage |
|
| 10:15 - 10:30 | Thomas G. Hofmann (Institute of Toxicology, Johannes Gutenberg University of Mainz) GERMANY A direct role for HIPK2 in homology-directed DNA repair and the regulation of PARP inhibitor sensitivity |
|
| 10:30 - 10:45 | Ana Rita Guedes (CECAV– Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro) PORTUGAL Could DNA damage be a useful biomarker of diagnosis and prognostic in human breast and colorectal cancer? |
|
| 10:45 - 11:00 | Bernd Kaina (Institute of Toxicology, University Medical Center, Mainz) GERMANY Senescence and cell death triggered by the DNA alkylation damage O6-methylguanine |
11:00 – 11:30
Coffee Break
| Session 08: Machine Learning | Wednesday 17th May 11:30 - 13:00 (Forum 1) | Chairs: George Johnson (Swansea University, UK) |
|---|---|---|
| 11:30 - 12:00 | Steve Bryce (Litron Labs) USA Introduction to Machine Learning in Genetic Toxicology |
|
| 12:00 - 12:30 | Paul Rees (Invited Speaker) (Swansea University) UK Deep Neural Networks to Automate Scoring Of The Imaging Flow Cytometry In-Vitro Micronucleus Assay |
|
| 12:30 - 13:00 | Joost Beltman (Leiden University) THE NETHERLANDS Towards a quantitative understanding of the DNA damage response through data-driven dynamical modeling |
| Session 09: New Challenges In Genotoxicity Assessment | Wednesday 17th May 11:30 - 13:00 (Forum 2) | Chairs: Ricard Marcos (Universitat Autònoma de Barcelona, SPAIN) & Vanessa Valdiglesias (Universidade da Coruña, SPAIN) |
|---|---|---|
| 11:30 - 12:15 | Alba Hernández (Invited Speaker) (Autonomous University of Barcelona) SPAIN Understanding the health risks of exposure to micro- & nano-plastics |
|
| 12:15 - 12:30 | Massimo Aloisi (University of L’Aquila) ITALY Biological effects of chronic oral exposure to polystyrene nanoparticles in Drosophila melanogaster |
|
| 12:30 - 12:45 | Jolanta Kwasniewska (University of Silesia Institution in Katowice) POLAND Recent achievements in micronuclei characterization |
|
| 12:45 - 13:00 | Maricel Marin-Kuan (Nestlé Research, Vers-chez-les-Blancs) SWITZERLAND Novel methodology to assess genotoxicity in Food Contact Materials (FCM) |
13:00 – 14:00
Lunch
| Pitch-poster Presentation 2 | Wednesday 17th May 14:00 - 14:30 (Forum 2) | |
|---|---|---|
| 14:00 - 14:05 | Milda Babonaitė (Department of Botany and Genetics, Institute of Biosciences, Vilnius University) LITHUANIA Evaluation of Cytotoxicity and Genotoxicity of Nano-sized Plastic Particles |
|
| 14:05 - 14:10 | Cynthia Recoules (DToxalim INRAE) FRANCIA Effect of cell treatment procedure on in vitro genotoxicity assessment |
|
| 14:10 - 14:15 | Mojgan Najafzadeh (University of Bradford) UK A novel form of gallic acid to improve the compound bioavailability and cancer |
|
| 14:15 - 14:20 | Alba Garcia-Rodriguez (Universitat Autònoma de Barcelona) SPAIN Drosophila melanogaster as bioindicator of microbiome dysfunction |
|
| 14:20 - 14:25 | Kristyna Tomasova (Biomedical Center, Faculty of Medicine in Pilsen, Charles University) CZECH REPUBLIC A modified alkaline comet assay to measure base excision repair in mitochondria |
14:30 – 16:00
Fritz Sobels & Early Career Awards
16:00 – 17:30
Poster Session 2 & Sponsor Visit
(while coffee is served)
17:30 – 18:30
EEMGS General Assembly
18:30 – 19:30
SEMA General Assembly
20:30 – 00:00
Congress Dinner
El Balneario - Baños del Carmen
C/ Bolivia, 26, 29018 Málaga
| Session 10: error-corrected Next-Generation Sequencing (ecNGS) | Thursday 18th May 9:00 - 11:00 (Forum 2) | Chairs: Vanessa Moraes de Andrade (Universidade do Extremo Sul Catarinense, BRAZIL) & Anthony Lynch (GSK, UK) |
|---|---|---|
| 9:00 - 9:35 | Jiri Zavadil (Invited Speaker) (IARC) FRANCE NGS and toxicogenomic signatures of human carcinogens |
|
| 9:35 - 10:10 | Patrick van Eijk (Invited Speaker) (Cardiff University) UK NGS applications to assess vector mediated genotoxicity in genetic medicine |
|
| 10:10 - 10:45 | Clint Valentine (Twinstrand Bio) USA Genomic Safety Assessment with ecNGS: The Next Generation |
|
| 10:45 - 11:00 | Anthony Lynch (GSK) UK ecNGS analysis of induced mutagenesis in the low dose region. Case studies with noteworthy nitrosamines |
11:00 – 11:30
Coffee Break
| Session 11: Advances In Regulatory Genotoxicology | Thursday 18th May 11:30 - 13:00 (Forum 1) | Chairs: Birgit Mertens (Sciensano, BELGIUM) & Antonio Guzmán (Alexion Pharmaceuticals, Inc., SPAIN) |
|---|---|---|
| 11:30 - 12:15 | Marc Beal (Invited Speaker) (Health Canada) CANADA Modern in vitro screening tools to enhance quantitative chemical risk assessment |
|
| 12:15 - 12:30 | Anouck Ingrid Thienpont (Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel) BELGIUM The GENOMARK transcriptomic biomarker demonstrates a high predictivity for genotoxic hazards and utility in potency ranking in human HepaRG™ cells |
|
| 12:30 - 12:45 | Ann-Karin Olsen (Norwegian Institute of Public Health, Division of Climate and Environmental Health) NORWAY Assessing DNA damage in Testicular Germ Cells in the Comet Assay |
|
| 12:45 - 13:00 | Michele Davigo (National Institute for Public Health and the Environment (RIVM), Centre for Health Protection) THE NETHERLANDS Assessing the DNA damage potential of cigarette and iQOS emissions in human bronchial epithelial cells |
| Session 12: Human Biomonitoring | Thursday 18th May 11:30 - 13:00 (Forum 2) | Chairs: Stefano Bonassi (IRCCS San Raffaele Roma, ITALY) & Blanca Laffon (Universidade da Coruña, SPAIN) |
|---|---|---|
| 11:30 - 12:00 | Gareth Jenkins (Invited Speaker) (University of Swansea) UK Understanding blood cell mutational biomarkers for biomonitoring and disease purposes |
|
| 12:00 - 12:15 | Lucia Migliore (University of Pisa) ITALY The importance of gene – environment interactions in Alzheimer disease and the emerging role of epigenetics |
|
| 12:15 - 12:30 | Vanessa Sousa (University of Porto) PORTUGAL Assessment of DNA damage in cumulus cells from infertile women using comet assay |
|
| 12:30 - 12:45 | Soňa Vodenková (Charles University) CZECH REPUBLIC Association of mitochondrial DNA copy number and telomere length with colorectal cancer patient outcomes |
|
| 12:45 - 13:00 | Mirta Milić (Institute for Medical Research and Occupational Health) CROATIA The use of combined different approaches in assessing the conditions and making prediction models in severely obese BMI ≥ 35 kg m-2 (FFQ, DII, anthropometric, biochemical and DNA damage parameters) |
13:00 – 13:30
Closing Ceremony
HUMN Workshop
The buccal micronucleus (MN) cytome assay – New Horizons for its implementation in human biomonitoring and clinical studies
Michael Fenech (University of South Australia), Siegfried Knasmueller (Medical University of Vienna Institute of Cancer Research), Stefano Bonassi (San Raffaele University)
| HUMN Workshop | Thursday 18th May: 14:00 - 17:30 (Forum 2) |
|---|---|
| 13:00 - 14:00 | Registration & Lunch |
| Early afternoon Session 14:00 - 15:40 | |
| 14:00 - 14:10 | Welcome & Overview of Workshop Goals Co-chairs: Michael Fenech (Genome Health Foundation, AUSTRALIA), Siegfried Knasmueller (Medical University of Vienna, AUSTRIA), Stefano Bonassi (IRCCS San Raffaele Roma, ITALY) |
| 14:10 - 14:40 | The biology of buccal cells and the buccal micronucleus (MN) cytome assay Claudia Bolognesi (Ospedale Policlinico San Martino, ITALY) |
| 14:40 - 15:10 | Use of buccal cytome assays in the occupational exposure studies Georg Wultsch (Medical University of Vienna, AUSTRIA) |
| 15:10 - 15:40 | Association of buccal MN cytome assay biomarkers with disease and their relevance for clinical studies Stefano Bonassi (IRCCS San Raffaele Roma, ITALY) |
| 15:40 - 16:00 | Coffee Break |
| Late afternoon Session 16:00 - 17:30 | |
| 16:00 - 16:30 | Impact of nutrition and life style on formation of micronuclei and other nuclear anomalies in buccal cells Siegfried Knasmueller (Medical University of Vienna, AUSTRIA) |
| 16:30 - 16:45 | Automation of the Buccal Micronucleus Cytome Assay Michael Fenech (Genome Health Foundation, AUSTRALIA) |
| 16:45 - 17:00 | Artificial Intelligence in Microscope-Based Imaging: Automation of the Buccal Micronucleus Cytome Assay? Christian Schunck (MetaSystems, GERMANY) |
| 17:00 - 17:30 | Discussion on knowledge gaps regarding the buccal MN cytome assay and a roadmap for its translation into practice (open to all participants) |