Toxicology
Projects and initiatives
HealthToxicologyIn vitro
RISKHUNT3R project – interview by TOXstreams
Many studies are focused on finding the next best tool or test to assess the risk associated with chemical exposure. That is all well and good, but even the perfect assay needs to be accepted by regulators before seeing the light of the day. And how do we do that? The guests in this webinar have some ideas on that as principal investigators of the EU project RISK HUNT3R. Prof. Bob van de Water, Dr Mirjam Luijten and Dr Andrew White explain what RISK HUNT3R is doing, what next generation risk assessment means and why it is so important. Click on the link in the video to watch the whole interview.
Expert interviews
HealthToxicology
Ecotoxicology explained - interview by TOXstreams
Toxicology is a complicated area where you have to figure out if a chemical is safe for the entire human population? Well, some researchers in this field go even beyond, and instead of studying the safety of substances on “just” people, they focus on any living being on the whole planet. In this TOXstreams interview ecotoxicologists Dr Adam Lillicrap from the Norwegian Institute for Water Research and Dr Kristin Schirmer from the Eawag Science and Technology and co-founder of aQuaTox Solutions GmbH Solutions will explain what and how they do this. Click on the link in the video to watch the whole interview.
Projects and initiatives
HealthToxicologyIn vitro
PrecisionTox project – interview by TOXstreams
What do nematodes, zooplanktons, clawed frogs, fruit flies, zebrafishes and humans have in common? Well, they are all part of the EU-funded project PrecisionTox. In this teaser for the TOXstreams interview, PrecisionTox researchers explain how they are combining non-traditional test species with molecular and computational methods to better protect our society from toxic chemicals. Prof. John Colbourne, the project’s coordinator, Dr Gaëlle Hayot, Christina Cramer von Clausbruch will tell all you want to know. Click on the link in the video to watch the whole interview.
Projects and initiatives
HealthToxicologyIn vitro
ONTOX project – interview by TOXstreams
Have you ever wondered how one can actually develop a new approach method (NAM) to replace animal testing in toxicology? The ONTOX project is creating not just one but six different NAMs. Indeed, this EU-funded project is focused on building NAMs to study repeated dose toxicity effects, an area of toxicology that still relies heavily on animal testing. Prof. Mathieu Vinken, the project’s coordinator, Jian Jiang, PhD, Anouk Verhoeven and Jonas van Ertvelde explain their work to TOXstreams. Click on the link in the video to watch the full episode.
Innovation examples
ToxicologyIn vitro
Combatting the worlds deadliest infections using groundbreaking human-mimetic tools
Combatting the worlds deadliest infections using groundbreaking human-mimetic tools.
Zika, dengue & other viruses are typically tested in monkeys & mice. But is using animals really the most effective way? Find out what Dr. David Pamies of the @jhucaat - along with his colleagues at @JohnsHopkins - are doing to upend the status quo.
More information on:
https://www.eurekalert.org/pub_releases/2019-06/hsi-ctw061319.php
and
https://www.frontiersin.org/articles/10.3389/fcimb.2019.00223/
Expert interviews
Toxicology
How do we use human data in risk assessment
In this video, EFSA explains how they do risk assessment and what the role of NAMs can be in this process.
Projects and initiatives
HealthToxicologyInnovationIn vitro
Cells4Thought: using iPSCs for neurodevelopmental health
The prevalence of neurodevelopmental disorders (NDDs), including cognitive impairments, is increasing worldwide with great impact on daily life quality. There is evidence that exposure to chemicals may contribute to the incidence of NDD. However, a causal link is lacking. Towards this goal, a human-relevant in vitro model system mimicking parts of brain development, such as neuronal network functioning, could be used for mechanistic research on how gene-environment interactions contribute to the development of NDD. This is going to be studied in the project Cells4Thought, using induced pluripotent stem cells form different individuals to study the effect of chemicals on neuronal differentiation.
Meetings & conferences
HelpathonsHealthToxicologyIn silico
ONTOX Hackathon: Hack To Save Lives And Avoid Animal Suffering
Artificial Intelligence (AI) in toxicology – a potential driver for reducing or replacing laboratory animals in the future. ONTOX project is looking for solutions and innovative ideas to move forward. Are you going to help ONTOX to hack into these complex challenges?
The hackathon will be held from 21 to 23 April 2024 in Utrecht Science Park. The whole event is open to a diverse community of forward-thinkers and problem-solvers interested in the intersection of AI and ethical toxicology. The goal is to bring together passionate individuals who seek innovative solutions to critical challenges in toxicology.
Read more about the hackathon and register here (https://ontox-project.eu/hackathon/).
Innovation examples
HealthToxicologyInnovationIn vitro
Human based 3D liver models
Human-based in vitro models are increasingly being used in the hepatology field. And in addition to the obvious ethical arguments, they offer several advantages over the classical animal models. One of them is the ability to perform mechanistic research at the molecular level in a well-controlled setting and reduce species differences. These liver-based in vitro models can range from simple monolayer cultures of hepatocytes to the liver-on-chips systems in which all liver cells are cultured in a 3D configuration on a microfluidic platform. Liver-based in vitro models must be selected on a case-by-case basis and should fit the purpose of the research, which might go from fundamental to translational research.
Innovation examples
HealthToxicologyInnovationIn vitro
Platform for in vitro airborne inhalation testing
The air-liquid interface (ALI) technique uses lung cells cultured on a tiny polymer membrane in a cup. On one side of the membrane is a liquid containing the medium necessary for the cells to survive, while the other side is in contact with air. This is similar to the situation in the human lung. The compound to be tested is administered via an aerosol, vapor, or gas to mimic the situation in human lungs. By monitoring different parameters in the cell model before and after the compound is added, it is possible to measure the effects on lung cells. Depending on the test to be carried out, the lung cells can come from different regions in the respiratory tract and even from a variety of people, including individuals who smoke a lot or have specific diseases such as chronic obstructive pulmonary disease or asthma.
In vitro ALI inhalation testing (https://doi.org/10.1021/acs.est.7b00493) adds value for e.g. pre-clinical trials and research in the pharmaceutical industry and testing (new) compounds for the chemical sector and beyond. The advantages of ALI inhalation testing are that it is a non-animal method, it reduces the use of in vivo experiments, pre-clinical testing with human-derived cell models is more realistic and limits clinical trial failures and it provides faster and more efficient testing of compound
Innovation examples
ToxicologyIn vitro
Stem cell differentiation assays for animal-free developmental neurotoxicity assessment
Victoria de Leeuw was a PhD candidate in the research group of prof. dr. Aldert Piersma at the RIVM and Institute for Risk Assessment Sciences at Utrecht University. Piersma's lab studies the effects of compounds on development of the embryo during pregnancy with, among other techniques, stem cell cultures. The project of Victoria was aimed to differentiate embryonic stem cells of mouse and human origin into neuronal and glial cells, which could mimic parts of differentiation as seen during embryonic brain development. These models were able to show some of the known toxic mechanisms induced by these compounds, congruent with what they we hypothesised to mimic. This provides mechanistic information into how chemical compounds can be toxic to brain development. Therefore, these two stem cell assays make a useful contribution to the animal-free assessment of developmental neurotoxicity potential of compounds.
Victoria is nominated for the Hugo van Poelgeest prize 2022 for excellent research to replace animal testing.
Meetings & conferences
ToxicologyIn vitroAdvanced
Biotransformation of proteratogenic anti-epileptics in the zebrafish embryo
The zebrafish (Danio rerio) embryo has gained interest as an alternative model for developmental toxicity testing, which still mainly relies on in vivo mammalian models (e.g., rat, rabbit). However, cytochrome P450 (CYP)-mediated drug metabolism, which is critical for the bioactivation of several proteratogens, is still under debate for this model. Therefore, we investigated the potential capacity of zebrafish embryos/larvae to bioactivate two known mammalian proteratogens, carbamazepine (CBZ) and phenytoin (PHE) into their mammalian active metabolites, carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. Zebrafish embryos were exposed to three concentrations (31.25, 85, and 250 μM) of CBZ and PHE from 51⁄4 to 120 hours post fertilization (hpf) at 28.5°C under a 14/10 hour light/dark cycle. For species comparison, also adult zebrafish, rat, rabbit and human liver microsomes (200 μg/ml) were exposed to 100 μM of CBZ or PHE for 240 minutes at 28.5°C. Potential formation of the mammalian metabolites was assessed in the embryo medium (48, 96, and 120 hpf); pooled (n=20) whole embryos/larvae extracts (24 and 120 hpf); and in the microsomal reaction mixtures (at 5 and 240 minutes) by targeted investigation using a UPLC–Triple Quadrupole MS system with lamotrigine (0.39 μM) as internal standard. Our study showed that zebrafish embryos metabolize CBZ to E-CBZ, but only at the end of organogenesis (from 96 hpf onwards), and no biotransformation of PHE to HPPH occurred. In contrast, our in vitro drug metabolism assay showed that adult zebrafish metabolize both compounds into their active mammalian metabolites. However, significant differences in metabolic rate were observed among the investigated species. These results highlight the importance of including the zebrafish in the in vitro drug metabolism testing battery
for accurate species selection in toxicity studies.