Research Lucia Vergauwen

Abstract

Chemicals risk assessors and managers are faced with data and knowledge gaps and lack of tools and methods, to speed up and prioritise risk assessments and capture risks from existing and emerging substances across regulatory domains. The lack of available or accessible information increases the risk of 'regrettable' substitutions and slows down the design of safer chemicals. A diverse landscape of regulatory frameworks and actors carrying out risk assessment of chemicals for their specific purpose has resulted in a fragmented approach. Risks to human and environmental health are still in certain cases considered separately, while in most cases they are inherently interrelated. To enable risk assessors and risk managers to respond to current and future challenges, the Partnership should stimulate research and innovation in chemicals risk assessment by developing a collaborative network with public research entities. A common research and innovation programme should be established by national and EU risk assessors and risk managers in consultation with relevant stakeholders (academia, industry, associations and others). Activities of the Partnership should be complementary and subsidiary to obligations under existing regulatory frameworks, and should coordinate with these as relevant. The Partnership should become a reference centre for research questions related to chemicals risk assessment, including those emerging from other Horizon Europe partnerships or missions. The Partnership is expected to establish relevant collaborations with other Horizon Europe partnerships and missions as set out in the working document on 'Coherence and Synergies of candidate European partnerships under Horizon Europe' as well as to explore collaborations with other relevant activities at EU and international level. The Partnership should align with EU-wide initiatives on open access and FAIR data.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: Bervoets Lieven
• Co-promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Co-promoter: Groffen Thimo
• Co-promoter: Poma Giulia
• Co-promoter: van Nuijs Alexander
• Co-promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

This PhD project will investigate life-stage specific effects in zebrafish embryos exposed to thyroid hormone system disrupting chemicals. Specifically, we study the impact on the function of the hypothalamus pituitary thyroid axis and the development of target organs. We use swim bladder and eye development as model organs and we distinguish between effects on early and late embryonic development. This knowledge is crucial to advance the use of the zebrafish embryo as alternative to animal testing in thyroid hormone system disruption research and in applications for chemical safety evaluation.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: Vergauwen Lucia
• Fellow: Van Dingenen Imke

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

ERGO presents a new approach that will support a paradigm shift in the regulatory use of standardized test guidelines (TGs) by breaking the existing wall between mammalian and non-mammalian vertebrate testing and assessment of endocrine disrupting chemicals (EDCs). The highly conserved thyroid system will be used as the "proof of concept", but also other conserved endocrine axes/systems such as the Retinoid X Receptor (RXR) and the Hypothalamus Pituitary Gonadal (HPG) axis can be adapted to the cross-vertebrate class approach. ERGO will investigate a battery of draft in vitro assays and evaluate thyroid-responsive biomarkers and endpoints (B/E) suitable for extrapolation of effects from fish and amphibian tests to humans and other mammals (and vice versa) and finally validate successful B/E for inclusion in existing in vivo or new in vitro OECD TGs. A cross-class adverse outcome pathway (AOP) network will provide the scientifically plausible and evidence-based foundation for the selection of B/E in lower vertebrate assays predictive of human health outcomes. In silico modeling and biotransformation data will support cross-vertebrate class effect extrapolation. Major outcomes of ERGO will be: 1) New thyroid-related B/E for inclusion in OECD TGs for improved identification of TDC. 2) An Integrated Approach to Testing and Assessment (IATA) of chemicals for TD based on a multi-class vertebrate AOP network connecting endocrine mechanisms in one vertebrate class to adverse outcomes in another class for safer regulation of EDCs. 3) A tool for TG end users, such as regulators and industry, to extrapolate thyroid effects between vertebrate classes. Implementation of the ERGO IATA strategy in regulations of EDC will make hazard and risk assessment faster, cheaper, simpler and safer and support industry in the development of EDC-free products beneficial for environmental and human safety.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

About 10-15% of all animals used as laboratory animals in Flanders are fish. While the assessment of animal welfare is well established for mammals, the optimal conditions for guaranteeing fish welfare are less known or documented. A formal framework for optimizing and monitoring zebrafish welfare does currently not exist. This project therefore aims to develop a guidance document providing scientific and practical instructions for improving zebrafish welfare in laboratory animal facilities. The guidance document will be relevant to animal caretakers, technicians, responsible scientists, members of ethical committees, and animal welfare inspectors.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: De Boeck Gudrun
• Co-promoter: Van Ginneken Chris
• Co-promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

There is currently an urgent need for new screening approaches to identify thyroid hormone disrupting chemicals, both in ecotoxicology and human toxicology. Toxicity testing in the 21st century increasingly relies on high throughput animal-free assays screening chemicals for their interaction with biological targets. While the thyroid system is highly conserved across vertebrate classes, conservation of the chemical susceptibility of the components of the thyroid system (enzymes, receptors) remains to be investigated. In this project, we will compare the deiodinase (the enzyme responsible for thyroid hormone (de)activation) inhibition potential of a set of test chemicals across zebrafish, pig, rat and man. This information is essential to bridge the gap between ecotoxicology and human toxicology and support the exchange of information.

Researcher(s)

• Promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

The presence of certain toxicants/chemicals can perturb the endocrine system and induce a variety of responses, some of which can cause severe adverse effects in humans and wildlife. In order to protect human health and the environment, it is therefore important to identify those substances that can cause adverse effects via disruption of the endocrine system. Availability of test methods is an important factor in our ability to identify the substances that cause adverse effects via disruption of the endocrine system and in ensuring a high level of protection of human health and the environment. To ensure that test methods are internationally and mutually accepted a test guideline development programme has been established under the auspices of the OECD. Despite the progress achieved on the development and validation of test guidelines for evaluation of endocrine disruptors over the last 20 years, there are still some gaps and weaknesses in the current test methods for evaluation of endocrine disruptors. The objective of this study is to develop study protocols for testing of endocrine disrupting effects in biotic systems to improve the identification of substances disturbing the endocrine system by enhancing already existing test guidelines.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

Nano-injection is a promising alternative exposure route for toxicological research using fish embryos. We recently started applying nano-injections and observed differences in toxicity compared to exposure via water. While it is plausible that uptake and biotransformation play a role in these differences, this has never been investigated. The aim of this project is to characterize and understand differences in toxicity following nano-injection compared to aquatic exposure. We will compare accumulation, biotransformation, molecular events and physiological effects after exposure of zebrafish embryos to the same chemical via both exposure routes. This information is essential to evaluate the applicability of this promising alternative exposure route in (eco)toxicology.

Researcher(s)

• Promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

This project aims to develop an alternative testing strategy to reduce the need for fish early life-stage toxicity tests (FELS) for the assessment of chronic toxicity of chemicals to fish, using the adverse outcome pathway (AOP) framework as a guidance for assay development. Currently, the FELS test (OECD TG 210) is one of the primary testing guidelines used to estimate the chronic toxicity of chemicals to fish. Results obtained using this TG are used to support risk assessment around the world. However, important limitations of this animal test are being recognized, including (1) the high numbers of fish used, (2) the relatively low-throughput, and (3) the lack of mechanistic information. In order to comply with the 3R principles, we are developing a non-animal testing strategy which includes both in vitro tests and in vivo whole organism alternative 120 hpf (hours post fertilization) ZFET (zebrafish embryo acute toxicity test) assays. One of the main research questions of this project is to what extent an assay development approach based on the AOP framework is capable of offering a mechanistic basis for selecting assays to develop an alternative testing strategy that allows the prediction of chronic FELS toxicity. This project is a follow-up of Cefic LRI-ECO20, and aims to validate assays that were developed during that project.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: Blust Ronny
• Co-promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

Endocrine disruption is a major concern for the health of wildlife populations. Although many studies have shown reproductive impairment as a consequence of endocrine disruption in adult fish, knowledge of the consequences of endocrine disruption for vertebrate embryonic and larval development is scarce. The zebrafish embryo is an ideal model system to investigate the fundamental mechanisms of endocrine disruption. We will first describe the timing of the normal embryonic activation of the hormone synthesis machinery, as well as the hormone profiles, during the early stages of vertebrate development, which has never been done so far. Secondly, using well-described endocrine disrupting compounds, we will specifically disrupt these profiles and propose mechanisms linking the changed profiles to observed developmental effects. We will then validate the proposed mechanisms of toxicity using targeted disruption techniques, including knockout and morpholino knockdown. This project will offer the information that is needed for follow-up projects to develop assays to specifically assess the risk associated with exposure to different classes of EDCs on embryonic and larval development, allowing discrimination among ER and AR agonism and antagonism, as well as aromatase inhibition. Such assays would fit perfectly within both EU and USA regulatory priorities for screening and prioritizing potential EDCs.

Researcher(s)

• Promoter: Knapen Dries
• Co-promoter: van Nuijs Alexander
• Co-promoter: Vergauwen Lucia
• Fellow: Periz Stanaćev Jelena

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

Several fish, amphibian and reptile species exhibit non-genetic sex determination, which is currently poorly understood. Recent advances have identified several genes and pathways involved based on expression patterns, but the functional role of these genes in sex determination and differentiation remains unclear. By endocrine disruption of this process, we will investigate the role of selected genes in sex differentiation in the zebrafish.

Researcher(s)

• Promoter: Vergauwen Lucia

Research team(s)

• Veterinary physiology and biochemistry

Project type(s)

• Research Project

Abstract

Aquatic organisms are constantly being exposed to changes in their environment. These changes comprise both natural fluctuations (such as changes in environmental temperature) as well as anthropogenic disturbances (such as chemical pollution). This PhD combines these 2 kinds of stressors, investigating the influence of environmental temperature on cadmum toxicity in zebrafish (Danio rerio). A wide set of analyses ranges from gene expression changes to changes in swimming performance.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Knapen Dries
• Fellow: Vergauwen Lucia

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: De Coen Wim
• Fellow: Vergauwen Lucia

Research team(s)

Project type(s)

• Research Project