Current Topics in Toxicology

Aim of the course and schedule

This course is intended for (registered) toxicologists who aim to stay informed about the latest advancements in their field. The upcoming edition will provide an overview of recent developments in Omics in Toxicology, Particle and Fibre Toxicology, and High Throughput Screening Approaches for Chemical Hazard Characterization. More detailed information is provided below.

Day 1 – October 17, 2024
12:30 – 13:30 Lunch and introduction
13:30 – 17:00 Topic 1: Omics in Toxicology
Prof. Dr. Theo de Kok (Maastricht University, The Netherlands)
Prof. Dr. Dick Sijm (NVWA – Netherlands Food and Consumer Product Safety Authority, Utrecht, The Netherlands)
Dr. Nicolaj Bischoff (Maastricht University, The Netherlands)
17:00 – 17:30 Drinks & networking
17:30 – 19:30 Topic 2: Particle and Fibre Toxicology
Dr. Roel Schins (IUF – Leibniz Research Institute for Environmental Medicine, Dusseldorf, Germany)
Prof. Dr. Flemming Cassee (Utrecht University / RIVM – National Institute for Public Health and the Environment, Bilthoven, The Netherlands)
20:00 – 22:00 Dinner

Day 2 – October 18, 2024
09:00 – 12:30 Topic 3: High Throughput Screening Approaches for Chemical Hazard Characterization
Prof. Dr. Bob van de Water (Leiden University, The Netherlands)
Dr. Giulia Callegaro (Leiden University, The Netherlands)
12:30 – 13:30 Lunch and evaluation

Presenters: Prof. dr. Theo de Kok (Maastricht University), Prof. Dr. Dick Sijm (NVWA), Dr. Nicolaj Bischoff (Maastricht University).

Aim: To demonstrate how the use of ‘omics approaches in toxicological reseach has evolved over time and how such techniques can be of added value in hazard identification and human health risk assessment.

Overview/Content: Omics techniques, particularly transcriptomics, are invaluable tools in toxicology for comprehensively understanding how toxicants affect biological systems. Transcriptomics focuses on studying the entire set of RNA transcripts within cells or organisms, offering a dynamic snapshot of cellular responses to toxic exposure. By analyzing transcriptomic data, researchers can identify genes that are upregulated or downregulated in response to toxicants, uncovering potential biomarkers of toxicity and elucidating underlying molecular mechanisms. Transcriptomics also enables the exploration of toxicant-induced alterations in signaling pathways, biological processes, and regulatory networks. Integration of transcriptomic data with other omics datasets enhances our understanding of toxicological responses at a systems level. Ultimately, transcriptomic analyses provide valuable information for predicting toxicological outcomes, assessing risks associated with chemical exposures, and developing targeted interventions for mitigating adverse effects on human health and the environment.

Method: An overview will be presented on the different ‘omics techniques that can be used to generate molecular data that provide insight in toxicological processes. A number of large project that apply such approaches will be introduced and examples will be provided. How this can contribute to risk assessment will be presented for the evaluation of food additive E171 (titanium dioxide) and we will organize a stakeholder debate representing positions from science, regulators and society in which participants will actively engage.

Outcome: The participants will gain insight into the different types of ‘omics techniques that are available for toxicological research, who these can be applied in the context of the development of NAMs, clinical and exposome research, and how ‘omics approaches can contribute to toxicological risk assessment.

Presenters: Dr. Roel Schins (IUF – Leibniz Research Institute for Evironmental Medicine, Düsseldorf) and Prof dr. Flemming Cassee (Utrecht University / RIVM)

Aim: This section of the course will focus on latest developments in the field of particle and fibre toxicology.

Overview/Content: Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. Over the past decades we have gained considerable experience in how particle properties and particle-biointeractions are linked to adverse human health effects. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles’ and fibres’ risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. We will address all these aspect in light of advanced and innovative nanomaterials and microplastics. In particular pitfalls related to interpreting in vitro tests (also referred to as new approach methodologies (NAMs)) will be addressed, which will be helpful when assessing data presented using these approaches.

Presenters: Prof. Dr. Bob van de Water (Leiden University) and Dr. Giulia Callegaro (Leiden University)

Aim: To teach participants the state-of-the art in advanced high throughput imaging and transcriptomics methods to uncover hazards for human safety assessment.

Overview/Content: The enormous number of chemicals that lack safety assessment requires fast, efficient, robust and cost effective methods to characterize potential hazards. Current understanding of human biology, mechanistic understanding of toxicity, advanced human test systems and innovative technologies including genome engineering, imaging technology and transcriptomics analysis and interpretation, now allows for this requirement and facilitate future Next Generation Risk Assessment (NGRA). We will introduce how mechanistic knowledge allows identification of biomarkers of toxicity and how these can be integrated in novel fluorescent reporter assays using advanced genome engineering technologies and applied in combination with automated live cell imaging to uncover chemical safety liabilities. Moreover, we will describe the application of high throughput transcriptomics using targeted RNA sequencing technologies and how this technology in combination with advanced human in vitro test systems can contribute to mechanism-based hazard characterization and support NGRA.

Method: After an introduction of the application of high throughput microscopy and reporter technology as well as high throughput transcriptomics-based approaches for hazard charactierzation, the participants will use a toxicogenomics dataset in combination with an intuitive toxicogenomics interpretation tool to qualify and quantify the mode-of-action of several selected chemicals.

Outcome: At the end of the workshop the participants will have insight how advanced mechanism-based screening methods based on high throughput imaging and transcriptomics can facilitate the characterization of hazards for safety assessment and be integrated in mechanism-based NGRA.

 

Coordinators: Prof. dr. ir. Juliette Legler and Prof. Dr. Flemming R. Cassee

Fee: € 510,- including dinner.

Please note that the course can be cancelled up to one month before its starting date, when the number of applications is below the minimum required. For general inquiries please contact the PET Office.

Developmental and Reproductive Toxicology
Cellular Toxicology