We do this with pure chemicals as well as human and environmental samples. In line with contemporary (eco)toxicological hazard and risk assessment practice, we strive to investigate the toxic actions of chemicals using mostly protein- and cell-based assays and zebrafish embryo models. The cell-based assays, including more complex assays using co-cultures in transwell systems and organoids, allow us to study mechanisms of toxicity and screen compounds and environmental samples for toxicity in human models. Zebrafish embryos enable us to study toxicity within an intact vertebrate organism linking toxic mechanism to health outcomes that are relevant for wildlife and humans. Our toxicological focus is mainly on endocrine, metabolic and neurological endpoints, such as reproduction and brain development. To enhance the acceptance of our methods in (regulatory) chemical safety assessment practices, we actively initiate and participate in validation studies across laboratories and development of OECD test guidelines, which are used globally for chemical safety assessment.
To investigate perturbations of these endpoints in our different models, we use molecular techniques e.g. transgenic models, reporter-gene assays, protein-binding and enzyme activity assays, in situ hybridization, qPCR, and metabolomic and lipidomic techniques. The gained mechanistic knowledge is applied to develop novel and/or improve existing in vitro bioassays that are either high-content (i.e. low throughput, but with high information potential) or high-throughput (i.e. the potential to rapidly screen many chemicals and mixtures for potential effect on a specific endpoint). In addition, this toxicological information can be used to substantiate mechanistic descriptions of toxicological health outcomes, or adverse outcome pathways (AOPs).
At higher levels of organization, we study the impact of toxicants on cellular processes, organ development and behavior of our models. Our state-of-the-art histopathology lab includes all relevant instruments for automated tissue processing, cutting and staining. Image analysis is performed with an automated slide scanner that produces high-resolution images of microscopical sections. Our confocal microscope is used to image our different transgenic zebrafish models to study the chemical impact on their development, e.g. their endocrine organs or nervous system. An automated video tracking device is used for behavior analysis of zebrafish embryos. We have developed several assays to assess the toxicity of endocrine disrupting chemicals (EDCs), such as bioassays for thyroid hormone transport, steroid hormone biosynthesis, oocyte development and (zebrafish) embryotoxicity.
In addition, we apply our bioassays to screen for potentially harmful compounds in a wide variety of matrices, such as house dust, drinking water, human breast milk, (cord) blood, cerebrospinal fluid, meconium and placenta. To date, relatively little is known about the risk of these chemicals in/via these matrices, especially for the newer chemicals that are in our living environment including nano- and microplastics. The effect-directed analysis (EDA) approach that is implemented at the department in a close collaboration between the EH&T and CH&E sections, couples chemical fractionation of the sample with high-throughput toxicological hazard assessment to facilitate the identification of chemicals responsible for responses observed for example in exposed zebrafish embryos or cells. Thereby, our research clearly addresses a scientific and societal need for the identification and subsequent risk assessment of yet unknown but bioactive constituents in chemical mixtures present in humans and the environment.
Projects
NeXED (Lisa Baumann, Timo Hamers, Pim Leonards)
Network for Cross-disciplinary assessment of Endocrine Disrupting Compounds
MERLON (Majorie van Duursen, Lisa Baumann)
Merging scientific evidence with regulatory practices and leveraging identification of endocrine disruptors using new approach methodologies
IMITHRA (Lisa Baumann)
Impact of thyroid hormonal system disruption on the health of rainbow trout intergenerationally exposed to PFAS
Panoramix (Timo Hamers, Marja Lamoree, Maria Margalef)
Providing risk assessments of complex real-life mixtures for the protection of Europe’s citizens and the environment
ZeroPM (Timo Hamers, Majorie van Duursen, Lisa Baumann)
Zero pollution of Persistent, Mobile substances
PARC (Timo Hamers, Majorie van Duursen, Marja Lamoree)
Partnership for the Assessment of Risks from Chemicals
AURORA (Majorie van Duursen, Virissa Lenters)
Actionable European Roadmap for early-life health risk assessment of micro-an nanoplastics
ATHENA (Timo Hamers)
Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies
FREIA (Majorie van Duursen, Virissa Lenters, Eva Sugeng)
Female Reproductive toxicity of endocrine disrupting chemicals: a human evidence-based screening and Identification Approach.
ECHA tender project (Lisa Baumann, Nora Bouftas)
Scientific and technical support work related to hazard assessment and identification, including regulatory support of work on CLP, Dossier and Substance Evaluation, POPs, DWD and future tasks under certain water protection directives. Contract-based funding for specific tasks
PAN (Nora Bouftas, Majorie van Duursen)
Developing Adverse Outcome Pathways for endocrine disruptors
Validation studies
TTR assay: Competitive binding assay assessing the ability of a test substance to displace T4 thyroid hormone from its transporter TTR
H295R steroidogenesis assay: measurement of steroid hormones in human adrenal cell line
PPAR-gamma assay: transactivation of the peroxisome proliferator-activated receptor gamma thyroid hormone system disruption assessment in zebrafish embryos