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 predominantly in vitro cell-based assays, zebrafish embryo and nematode models. The cell-based assays, including more complex assays using cocultures 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. The nematode assays allow us to explore the impact of chemicals throughout the whole life of the worm (from birth to death), and how they can link to human-relevant endpoints such as aging, reproduction, neurodegenerative disease and obesity.
To investigate perturbations of these endpoints in our different models, we use molecular techniques e.g. RNAi, knock-out and transgenic models, reporter-gene assays, 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 zebrafish and C. elegans models to study the impact on their development, e.g. their endocrine organs or nervous system. An automated video tracking device is used for behavior analysis. 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, 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. 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 process of chemicals responsible for the observed bioassay response. Thereby, our research clearly addresses a scientific and societal need for risk assessment of mixtures of unknown constituents for humans and the environment.