Industry Hosted Sessions
Monday, September 19, 2022
12:00 PM - 13:00 PM
Chairperson(s): Abby Li (Exponent, Inc., USA)
Glyphosate products are widely used to combat weeds in agriculture and horticulture. Neurological outcomes spanning the age spectrum, including neurodevelopmental disorders and chronic neurodegenerative diseases such as Parkinson disease, have become increasingly prominent issues in human health risk assessments of pesticides, including glyphosate. Since glyphosate is measured in a number of food products and water sources, systematic reviews of the human epidemiological and animal neurotoxicology studies are needed to evaluate the potential neurotoxicity of glyphosate. This symposium will begin with a brief introduction of exposure considerations that are key to evaluating the quality and relevance of human and animal studies for risk assessment purposes. This will be followed by two lectures on the current state of the human and animal literature on the effects of glyphosate exposures on neurological outcomes. A weight-of-evidence approach with a priori quality criteria will be described, the results of the analysis by two separate panels of epidemiologists and neurotoxicologists will be summarized, and recommendations for how future studies can be more useful for risk assessment purposes will be discussed.
Abby Li (Exponent, Inc., USA):
The Who What Why of Glyphosate Exposure in Evaluating Neurotoxicology Studies for Risk Assessment (Intro)
Ellen Chang (Exponent, Inc., USA):
Application of US EPA Office of Pesticide Programs (OPP) Framework for Evaluation of Human Epidemiological Literature on Glyphosate Neurotoxicity
Virginia Moser (Independent Consultant, USA); Jason Richardson (Robert Stempel College of Public Health and Social Work at Florida International University, USA); Keith Morris-Schafer (Exponent, Inc., USA); Abby Li (Exponent, Inc., USA):
Expert Panel Review of the Neurotoxicology of Glyphosate in Mammalian Systems for Risk Assessment Purposes
Chairperson(s): Thierry Langer (University of Vienna, AT), Jacques Richard (Sanofi Aventis, FR)
The adverse effects of pharmaceuticals on the central or peripheral nervous systems are poorly predicted by the current in vitro and in vivo preclinical studies performed during Research and Development (R&D) process. Therefore, increasing the predictivity of the preclinical toolbox is a clear need, and would benefit to human volunteers/patients (safer drugs) and Pharmaceutical Industry (reduced attrition). By combining top level scientists in neurobiology/toxicology with successful software developers, the NeuroDeRisk | Neurotoxicity De-Risking in Preclinical Drug Discovery Consortium will aim at tackling three of the most challenging adverse effects: seizures, psychological/psychiatric changes, and peripheral neuropathies. Our approach will be global, starting with an in-depth evaluation of knowledge on mechanisms of neurotoxicity (biological pathways as well as chemical structures and descriptors, using in particular historical data). Then we will search
for innovative tools, assays and studies covering in silico, in vitro and in vivo approaches. This will include in particular:
molecular design platform, artificial intelligence, human induced pluripotent stem cells, blood-brain-barrier models, immunohistochemistry, transcriptomics, RNA editing biomarkers, video-monitoring and telemetry of animals, pharmacokinetics, etc. The last step will aim at combining these tools in an integrated platform for better risk-assessment and decision-points throughout R&D process, and thus better protection of human volunteers and patients.
Thierry Langer (University of Vienna, AT):
Overview of the Innovative Medicines Initiative NeuoDerisk Project
Ludmilla Mazelin-Winum (Sanofi R&D, FR):
Work Package 1 – Improving the Preclinical Prediction of Seizures
João Pedro Silva (UCIBIO-REQUIMTE, Faculty of Pharmacy, University of Porto, PT):
Work Package 2 – Improving the Preclinical Prediction of Psychological/Psychiatric Adverse Effects
Lorenzo Do Cesare Mannelli (University of Florence, IT):
Work Package 3 – Improving the Preclinical Prediction of Peripheral Neuropathies
Sharon Bryant (Inte:Ligand Software Enwicklungs und Consulting GmbH, AT):
The NeuroDeRisk Toolbox: DeRisking Chemical Structures for Neurotoxic Adverse Outcomes
Chairperson(s): Janet Kelly (WuXi AppTec, USA)
What is animal welfare and why is it important during your toxicology program? There are excellent opportunities to advance the welfare of animals by eliminating pain and distress, and systematically reducing the number of animals necessary for individual studies by implementing the 3Rs.
Janet Kelly (WuXi AppTec, USA):
The Importance of Animal Welfare During Your Toxicology Program
Tuesday, September 20, 2022
12:00 PM - 13:00 PM
Chairperson(s): Andy Forreryd (SenzaGen AB, SE)
The field of in vitro skin sensitization assessment is rapidly evolving, and novel methods are developed to increase predictivity, broaden the applicability and to provide reliable quantitative and qualitative potency assessments. This symposium will introduce the audience to GARD®, the genomic-based technology, and discuss the new opportunities it brings to the field of in vitro skin sensitization testing.
The session will start with an introduction to the key elements of the GARD technology followed by reviewing the performance and applicability of the GARDskin assay for in vitro skin sensitization testing. Results from the assessment of “difficult-to-test” samples including metals, complex mixtures, pre- and pro-haptens, surfactants and hydrophobic substances will be presented. Moreover, the capability of GARD for quantitative skin sensitizing potency assessment will be exemplified by several industry-sponsored case studies.
In summary, this symposium will highlight the performance and applicability domain of GARD and discuss its potential for addressing remaining challenges within R&D and regulatory skin sensitization testing.
The participants will have the opportunity to learn more about the following:
- Key elements of the GARD technology.
- Quantitative potency assessments on a continuous scale for use as point-of-departure in already established risk assessment procedures.
- The applicability domain of GARDskin and its performance for “difficult-to-test” samples including metals, complex mixtures, pre- and pro-haptens, surfactants and hydrophobic substances.
- User cases from industry-sponsored studies to exemplify how GARD can be used for R&D and regulatory testing.
About the GARD technology platform
GARD – Genomic Allergen Rapid Detection® – is a next-generation, non-animal-based testing platform for identification and potency assessment of chemical sensitizers. The GARD platform brings novel elements to the field of regulatory toxicology, and integrates state-of-the-art technological components, including human immunological cells, specific genomic biomarker signatures and machine learning-assisted classification models. As a result, GARD comprises an accurate, cost-effective and efficient method for assessment of skin sensitizing properties of neat chemicals, complex mixtures and medical devices and may successfully be applied throughout the product life cycle.
Andy Forreryd (SenzaGen AB, SE):
In vitro skin sensitization testing: new opportunities for hazard and quantitative potency assessment using genomics and machine learning technolog
- Derive clinically relevant translational end point measurements
- Avoid missing rare or human-specific metabolites
- Generate mechanistic signatures of toxicity
- Model the effects of acute and chronic dosing regimens
- Assess DILI responses of specific patient populations (e.g. patients with fatty liver disorders)
- Understand interactions between organs, such as inflammation, which drive disease and enhance certain toxicities