Consortium

Wageningen University & Research

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Wageningen University & Research (WUR) is one of the leading European universities in Life Sciences. It does so through interdisciplinary research and teaching, combining efforts of various fields of natural and social sciences. The scientific quality of the institute is affirmed by the prominent position occupied in international rankings. The last 19 years WUR was considered to be the best university based on student rankings in the Dutch Keuzegids Universiteiten. At WUR, more than 10,000 students are enrolled.

The university houses state-of-the-art research equipment for a broad range of life science studies and which are essential for the Create2Solve BID project. This includes a suite of analytical equipment including LC-MS/MS, QTOF, GC-MS, HPLC-UV/fluorescence and a radiolabelling lab as well as high-end cell culture, molecular biology and microscopy facilities.
Nynke
Dr. Nynke Kramer

  • Associate professor in toxicology at Wageningen University and Research
  • Project leader of the BID project
  • Expert in Quantitative in Vitro to in Vivo Extrapolation (QIVIVE)
WUR is the project leader of the BID project.

WUR is responsible for overseeing the research performed in the project, as well as applying the in vitro assay results to quantitative in vitro to in vivo extrapolation (QIVIVE).

RIVM

RIVM, the Dutch National Institute for Public Health and the Environment, works towards a healthy population living in a sustainable, safe and healthy environment. RIVM pursues those goals based on independent scientific research.

Working with our commissioning clients, we identify the research that is needed and conduct studies accordingly. We provide advice to the government, to professionals and to members of the public, and share our knowledge. This is how RIVM supports society in staying healthy and keeping our environment healthy.
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Dr. Yvonne Staal

  • Scientist at the Centre for Health Protection, Department of Innovative Testing Strategies
  • Expert in in vitro models for inhalation toxicity and mechanism-based toxicity
Peter Bos (MSc)

  • Senior Risk Assessor at the Centre for Safety of Substances and Products
  • Expert in risk assessment of inhalation exposures and in application of animal-free innovations in risk assessment
Evert Duistermaat

  • Technician inhalation toxicity
  • Expert in design and generation of inhalation test atmospheres and equipment
Dr. Véronique de Bruijn

  • Scientist at the Centre for Health Protection, Department of Innovative Testing Strategies
  • Expert in in vitro models for the gastrointestinal tract and physiologically-based kinetic modeling
The responsibility of RIVM will be to develop closed chambers that will be used for exposure to (semi-) volatile compounds.

In addition, RIVM will be involved in the inter-laboratory comparison for patrician controlled dosing and closed chamber experiments.

Furthermore, RIVM is responsible for dissemination of the project results to OECD platforms and JRC contacts to facilitate regulatory update of better in vitro dosing methods in guidelines.

Institute for Risk Assessment Sciences

The Institute for Risk Assessment Sciences (IRAS) is an interfaculty research institute within the faculties of Veterinary Medicine, Medicine and Science at Utrecht University, the Netherlands. The institute is supported by the National Institute for Public Health and the Environment (RIVM) and TNO Research and advice. The mission of IRAS is to provide education and conduct research in the field of health risks posed to humans by exposure to biological and physical agents (e.g. pathogens and particles), and chemical substances in the environment, at work and in the food chain. The Institute also studies effects on ecosystems.

The research within the Create2Solve BID project is performed within the Toxicology division of the Institute, where research focus is on toxicological mechanisms and exposure assessment. The exposure assessment group led by Chiel Jonker tries to predict and quantify actual exposure to chemicals in the lab (in vitro and in vivo assays) and in the environment. Fate of chemicals at both scales is investigated in terms of partitioning processes and with the help of chemical analytical techniques (GC-MS, LC-MS/MS), passive sampling/dosing, and modeling tools. Emphasis is on developing new approaches and tools for predicting and quantifying exposure, aiming to contribute to improved chemical risk assessment for humans and the environment.
Chiel Jonker
Dr. M.T.O. (Chiel) Jonker

  • Senior researcher and consultant in exposure assessment at IRAS
Within the BID project, IRAS will be responsible for developing the partition-controlled dosing and the non-depletive in vitro systems, as well as for performing the chemical analyses and determining exposure concentrations in all tests.

Furthermore, the Institute will contribute to the chemical selection, creation of the database, the chemical property cut-off assessment, closed chamber system development, and the interlaboratory transferability study.

Vivaltes

Vivaltes is a biotechnology company founded in 2016 and located in Bunnik, the Netherlands. Vivaltes offers in vivo testing of compound effects in C. Elegans, as well as data science solutions. These include: evolutionary cross-species conservation mapping, pathway mapping, statistical data analysis, metabolomics, RNAseq, microarray analysis, and biological data mining.

Vivaltes has experience with data science topics such as data mining, creating dashboards, and data management (to ensure FAIR data principles). Vivaltes has successfully completed previous data science projects, such as DARTpaths (An in-silico platform for cross-species integration of compound-induced phenotypic endpoints to predict molecular mechanisms of action) and Create2Solve phase I (Proof of concept automated pipeline to collect available (literature) data on chemical and biological properties of compounds).
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Dr. Marjolein Wildwater

  • Founder & General Director at Vivaltes
  • Expert in Developmental Biology, Toxicology, and Business Development
Dr. Eefje Poppelaars

  • Lead data scientist at Vivaltes
  • Project Manager for the Better In Vitro Dosing project
  • Expert in data mining, data analysis, and visualization
The responsibility of Vivaltes will be to establish a database that enables us to:

  • Collect data on chemical and biological properties of compounds (i.e., critical parameters for QIVIVE and the decision tree) from public databases and the experimental data generated by the Better In Vitro Dosing project;
  • Create and validate a decision tree for choosing assay set-ups;
  • Implement computational modelling to predict internal concentrations and in vivo toxicity (QIVIVE); and
  • Combine all knowledge in a proof-of-concept interactive local dashboard.

Toxys

Toxys is a global leading expert that develops and offers a broad spectrum of unique animal-free laboratory tests for the safety assessment of novel medicines, chemicals, cosmetics and food. We are experts in the fields of genotoxicity, developmental toxicology and mechanistic toxicity testing. We develop assays with the focus on understanding the mode-of-action of toxic compounds.

Our ToxTracker® assay accurately identifies genotoxic compounds, ReproTracker® detects developmental toxicity and the ToxProfiler™ assay provides a broad toxicity profile of compounds. Toxys is internationally recognised for its scientific expertise, high quality results and responsiveness.
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Dr. Giel Hendriks

  • CEO of Toxys
  • Expert in Genetic Toxicology
Dr. Marit Hoogenboom-Geijer

  • Scientist at Toxys
  • Expert in DNA damage repair and the transcription stress response
Nynke Moelijker

  • Associate Scientist at Toxys
  • Expert in in vitro toxicity assays
Toxys will contribute our cell-based assay technologies such as the ToxTracker and ToxProfiler assays. We will be performing the exposure protocols so that the observed toxicity accurately reflects the exposure levels of chemicals relevant to human health. Through our expertise, we will conduct exposure protocols within our cell assays and continually optimize them to achieve the most reliable and informative results. The combined efforts of our team will enable us to provide valuable insights into the safety and potential risks associated with chemical substances.

ToxTracker® is a unique stem cell-based reporter assay for reliable genotoxicity and carcinogenicity hazard identification. On top of superior sensitivity and specificity for the detection of genotoxic compounds, the ToxTracker assay provides insight into the mode-of-action of genotoxicity. The assay can discriminate between direct DNA reactivity and indirect genotoxicity related to oxidative stress or protein damage and can identify clastogenic and aneugenic compounds.
ToxProfiler™ is a human cell reporter assay that can accurately quantify the cellular stress responses that are induced by chemicals. The unique combination of seven fluorescent reporter cell lines for oxidative stress, genetic stress, ER stress, autophagy, ion stress, protein stress, and inflammation are applied to generate a toxicological fingerprint and provide insight into the toxic mode-of-action of compounds.

These unique animal-free in vitro assays provide reliable and accurate toxicity information that is relevant to human health. The assays are used for early compound screening, follow-up testing and mode-of-action assessment, potency ranking, and chemical read-across. They are particularly useful in weight-of-evidence (WoE) and adverse outcome pathway (AOP) approaches for chemical safety assessment.

Contact us

If you want to know more about the Better In Vitro Dosing project or contact any consortium partner individually, please send an e-mail to both:

  • Dr. Nynke Kramer (Project Leader): nynke.kramer@wur.nl
  • &
  • Dr. Eefje Poppelaars (Project Manager): es.poppelaars@vivaltes.com

Sponsors

The Better In Vitro Dosing project is sponsored by:

Advisory board

The Better In Vitro Dosing project is advised by: