When:  Thursday, October 8, 2020 @ 12pm EDT
Presenter:  Dr. Mel Andersen

Differential gene expression analysis (DEGA) has proved useful for assessing modes of action (MOAs) with various compounds both following in life exposures to intact animals and with in vitro exposures of cells in culture. Various tools have been developed over the past decade or so to assist in the analysis of these patterns of differential gene expression, including heatmaps, pathway enrichment analysis, benchmark dose estimations and network representations of affected pathways using different ontologies. MOAs inferred from using these gene expression results have sometimes confirmed expectations from conventional toxicity testing and sometimes proved divergent, giving a more comprehensive look at the affected biology with compounds such as styrene, dichloromethane and vanadium pentoxide. In this webinar we discuss modes of action inferred from gene expression studies in relation to dose response modeling, dose-dependent transitions, pathway perturbations and comparing results from one treatment condition with another. The application of these DEGA tools to both in vivo and in vitro patterns of gene expression will likely uncover subtle differences in response among even similar compounds and also provide new tools for assessing the biological consequences of exposures to bioactive compounds. Toxicologists and risk assessors need to be prepared for surprises as these new biological tools are applied to assess MOA even for well-studied compounds.

The objective of the workshop will be to foster knowledge exchange, networking, and discussions on the concept of the application of the AOP programme to the radiation community. Experts from chemical toxicology will provide experiences on the framework through interactive discussions. The workshop will introduce the AOP concept, how it is being used in other disciplines and areas where it can support the radiation community.

The scientific program consists of 13 topic sessions chaired by renowned colleagues in the field. Each of these sessions is arranged to encourage questions and exchanges between presenters and participants. Thanks to the international scientific committee, that developed the program, there will be the opportunity to discover the most remarkable innovations from all over the world, from fundamentals in microfluidics including cells on a chip to the most recent advances in instrumentation or couplings with CE or LC; from sample preparation and clinical applications to «omics».

At this one-day symposium we would like to paint a picture of the status quo on pesticide exposure and hazard assessment by inviting the leading Swiss experts from the research, regulatory and industry communities. In light of the upcoming popular initiatives aiming to restrict or ban the use of synthetic pesticides, what is the current state of the evidence on the health hazards of pesticides? Considering the public concern with pesticides, we would further like to give some insight into the perspectives of risk perception, communication and management. Finally, we would like to discuss how published research (in vitro, in vivo, epidemiology) on potential adverse health effects of marketed pesticides can have a regulatory impact.

See programme for further information.

Scheduled to take place from 12:30 – 14:00 p.m. CEST over three days.

The lunch webinar is jointly organised by Charite 3R, 3Rs-Centre Utrecht Life Sciences, the Swedish 3Rs Centre, the Danish 3R-Center, the NC3Rs, and the Swiss 3RCC. In 2020, this webinar will replace our Swiss 3Rs Day. Researchers funded by the six centres will be showcasing 3Rs projects from across Europe. Everybody using animals or interested in supporting the 3Rs from all career stages is encouraged to attend. The Swiss veterinary federation accredited the 3Rs webinar for a half day of continued education.

Topics include COVID-19, Predictive Toxicology and Safety Assessment Hackathon (Github, Web meeting and Slack). Supported by online tools for virtual poster presentations, webinars, hackathon, and communications. Deadline for poster submission is 31 August 2020.

Le programme provisoire est disponible ci-joint ou sur le site du ccCTA en cliquant sur ce lien, et il est possible de s'inscrire dès maintenant ici.

The webinar explains how novel methodologies are developed and approved through expert committees, eventually becoming internationally accepted standard methods used by governments, industry and independent laboratories to assess the safety of chemicals.

The webinar is relevant for any stakeholder interested in how chemicals are developed and demonstrated as safe for market, within a global framework of countries.

Wed, September 16, 2020, 2:00 PM – 3:30 PM CEST

This virtual meeting will include a perspective from Bob van de Water (University Leiden, DESI) and a discussion session. 

High drug attrition rates are the main cause for the (exponentially) increasing healthcare cost. The lack of predictive in vitro models to either accurately test drug efficacy or determine toxic side effects in an early phase of drug development is causing this high failure rate. At Leiden University we developed the innovative SafeDESIgn reporter platform that we use to accurately assess the efficacy and/or safety of chemicals. The generated fluorophore reporter cell lines can be imaged with a confocal microscope over time so that we can accurately quantify the early dynamic adaptive signaling changes. By doing so we can not only determine if a chemical at a certain concentration is toxic, but also which adaptive/adverse pathways are activated. This is crucial information if we want to predict human safety levels for these chemicals.

This virtual meeting will include a perspective from Laszlo Urban (Novartis) and a discussion session. 

Excipients, considered “inactive ingredients”, are a major component of formulated drugs and play key roles in their pharmacokinetics.  Despite their pervasiveness, whether they are active on any targets has not been systematically explored.  We computed the likelihood that approved excipients would bind to molecular targets.  Testing in vitro revealed 25 excipient activities, ranging from low-nM to high-μM.  Another 109 activities were identified by testing against clinical safety targets.  In cellular models, five excipients had fingerprints predictive of system-level toxicities.  Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency. While most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets.