Research Adrian Covaci

Abstract

Ion mobility-high resolution mass spectrometry (IM-HRMS) is the next-generation analytical platform in research and industry. Unlocking its full potential across applications as varied as biotherapeutics, environment and food safety requires not only pushing back the frontiers of instrumentation, fundamental understanding and applications – but harmonisation is essential. To achieve this, current shortcomings in data collection, analysis and reporting across instrument types, laboratories and research areas need to be scrutinised and overcome. The MobiliTraIN Doctoral Network will form 10 Doctoral Candidates(DCs) who will bring a new fundamental understanding of IM-HRMS, provide reference materials and guidelines for standardisation, develop state-of-the-art methods for the application of IM HRMS in biopharmaceutical development, biological 'omics studies, and nontarget screening of contaminants, and lay the foundations for IM-HRMS adoption in industry. Through an interdisciplinary research programme, including an open science approach and training in technical, business and transferable skills, the MobiliTraIN DCs will become leading experts in ion mobility with a unique skill set to successfully advance their careers while supporting Europe's innovation capacity. Building on existing collaborations and research excellence covering the entire innovation chain of IM-HRMS development and application, MobiliTraIN unites 8 academic institutions, 3 leading instrumentation companies, 1 regulatory agency, 1 pharma industry leader and 5 SMEs from 8 countries. With complementary expertise, know-how and mentoring experience, our consortium is ideally suited to unveil the potential of IM-HRMS as a key technology for safer therapeutics, better understanding of complex disease progression and improved monitoring of food, water and public health safety

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project will extract information from urban wastewater regarding (il)licit drug use in communities, with a focus on new and emerging trends. The 2021 European Drug Report from the EMCDDA acknowledges that new and alternative monitoring tools are needed to increase the knowledge on the use of emerging substances such as ketamine, (non-pharmaceutical) benzodiazepines and opioids. This project will help to implement the wastewater-based epidemiology (WBE) approach to fill this knowledge gap. In first instance, a list of relevant substances and their biomarkers (parent compounds and/or metabolites) will be selected based on literature search and contacts with relevant partners (e.g. EMCDDA, Sciensano). Based on this list, multi-residue robust analytical procedures based on sample preparation (micro-solid-phase extraction) and liquid chromatography coupled to (high-resolution) mass spectrometry (LC-(HR)MS) will be developed and validated according to the EMA guidelines for the analysis of these biomarkers in urban wastewater. Long-term daily influent wastewater sampling and analysis in selected communities in Belgium will result in information on the spatial and temporal variations in the consumption of the selected substances and in the set-up of the most optimal sample strategies for large-scale WBE applications.

Researcher(s)

• Promoter: van Nuijs Alexander
• Co-promoter: Covaci Adrian
• Co-promoter: Poma Giulia

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a collaboration between European Monitoring Center for Drug and Drug Addiction and the Toxicological Center for the analysis of various drugs of abuse of wastewater samples collected in Georgia

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Extensive knowledge of contaminants of emerging concern (CECs) which humans are exposed to is highly required. Wastewater-based epidemiology (WBE) consists of the analysis of chemical markers for internal and external exposure in influent wastewater (IWW) and can be employed as a complementary approach to map the exposome in the general population. Due to the low concentration levels of CECs in IWW and the complexity of the matrix, there is a need for novel multidimensional chromatographic and high resolution mass-spectrometric approaches to accurately and precisely identify and quantify CECs in IWW. By applying novel analytical techniques (e.g., two-dimensional chromatography, ion-mobility mass spectrometry and high resolution mass spectrometry), the STYX project will acquire fundamental knowledge on various aspects related to human exposure to novel CECs using a WBE approach. Additionally, this project will unify and harmonize suspect screening and target analytical workflows for detection and identification of CECs and their metabolites in IWW to assess internal and external exposure to CECs in different communities. To achieve this, innovative sample preparation methods will be developed and validated to extract the CECs and metabolites from IWW and suspended particulate matter. Furthermore, systematic and comprehensive investigation of spatio-temporal trends will elucidate patterns of exposure to CECs and prioritize locations with a high burden of CEC exposure.

Researcher(s)

• Promoter: van Nuijs Alexander
• Co-promoter: Covaci Adrian
• Fellow: Boogaerts Tim

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Belgian and European citizens are exposed to multiple environmental stressors, such as chemical pollution, noise or lack of green space. The actual PFAS crisis in Flanders illustrates the urgent need for scientific evidence to shape environment & health policy making. EIRENE-Flanders is the Belgian hub of EIRENE RI, the European Environmental Exposure Assessment Research Infrastructure. In line with the holistic 'exposome' approach, it will allow to capture the complex interactions between environmental exposure, lifestyle and socio-economic variables, their impact on biological processes in the human body and effects on human health. It provides the infrastructure for large scale collection of human samples and data, efficient measurements of large sets of chemicals, metabolites and proteins, connection to existing datasets, and use of advanced bioinformatics and data science methods to process these large amounts of data. EIRENE-Flanders will contribute to reduce the environmental burden of disease through scientific evidence for environmental, chemicals, food safety and preventive health policies both at Flemish and at European level, and personalised medicine approaches.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Jorens Philippe

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Per- and polyfluoroalkyl substances (PFAS) are chemicals globally present in the environment and biota, as a result of their massive production and use in numerous applications, such as food contact paper, fire-fighting foams, textiles, construction and cleaning products. Their bioaccumulative and persistent properties have led to global regulatory measures for PFOS and PFOA. These are the most frequently detected legacy PFAS and their concentrations are still very high in the environment and biota. In addition, there are many emerging PFAS alternatives developed, with similar structures and chemical properties, not yet regulated and hence used unrestrictedly. However, very little or no information is available on the bioavailability, biomagnification and toxic effects of these emerging compounds, particularly for the terrestrial environment. PFAS may thus accumulate in the environment, posing risks to organisms. There are also many uncertainties on which factors might influence the bioavailability and biomagnification, especially of emerging PFAS. The identification of emerging PFAS, which have largely replaced the legacy PFAS, would allow us to investigate the environmental relevance of currently-used PFAS, as well as to characterize possible point sources. Detailed field studies on soil, plants, invertebrates (e.g. earthworms, woodlice, caterpillars, snails, slugs, and spiders), and great tits (Parus major; a songbird model species) planned in this project will provide us with: 1) an overview of the distribution of legacy and emerging PFAS present in the terrestrial environment near a fluorochemical polluting hotspot in Antwerp, 2) how the concentrations in the food chain are influenced by soil properties, and 3) their potential toxicity in key model species. In addition, experimental lab studies with PFAS and elevated temperature (T) as stressors on terrestrial invertebrates and plants will be performed to: 4) disentangle causal links from confounding effects regarding the soil properties, 5) verify whether or not increased T and PFAS have an additive toxic effect when combined, and 6) create a mechanistic framework explaining the underlying subcellular basis of root growth responses towards PFAS/increased T in the plant model species Arabidopsis thaliana. This project will allow us to understand the bioavailability and mechanism of the toxicity of emerging and legacy PFAS in plants, invertebrates, and birds and will offer instruments for regulators to assess the environmental risk and potential effects on human health.

Researcher(s)

• Promoter: Bervoets Lieven
• Co-promoter: Covaci Adrian
• Co-promoter: Eens Marcel
• Co-promoter: Prinsen Els
• Co-promoter: Vissenberg Kris

Research team(s)

• Ecosphere

Project type(s)

• Research Project

Abstract

This policy-oriented scientific research generates new human biomonitoring data and data from environmental measurements to examine to what extent and how adolescents in Flanders are exposed to environmental pressure and what this exposure does to the body. The study design is interdisciplinary. All Flemish universities, VITO, PIH and INBO contribute; VITO is the research coordinator. In this configuration, CRESC takes the lead of the social sciences aspects, including the research of socio-stratification in participation rates and study results, of risk perception, risk communication and stakeholder involvement in the study.

Researcher(s)

• Promoter: Bergmans Anne
• Co-promoter: Bervoets Lieven
• Co-promoter: Covaci Adrian
• Co-promoter: Crabbé Ann
• Co-promoter: Groffen Thimo
• Co-promoter: Vandermoere Frederic
• Co-promoter: Verschraegen Gert

Research team(s)

• Centre for Research on Environmental and Social Change

Project type(s)

• Research Project

Abstract

In the indoor environment, children are exposed to many contaminants of emerging concern, many of them being largely understudied. Two groups of such contaminants, namely the high molecular weight phenolic antioxidants (HMW SPA) and the organic phosphite antioxidants (OPA), have received limited attention. Human exposure to these novel antioxidants (AOXs) has not yet been investigated in Europe. Therefore, this project aims to develop mass spectrometric methods to assess human exposure to novel AOXs, including the first human biomonitoring assessment on AOX metabolites. These innovative methods will employ liquid chromatography coupled to tandem mass spectrometry (MS/MS), including target and non-target MS screening and novel acquisition approaches, such as iterative MS/MS. Different actions will be undertaken to assess the exposure of children to novel AOXs in the indoor environment. First, the degradation and human biotransformation products of novel AOXs will be identified and quantified. Second, in vitro bioaccessibility studies will allow for the implementation of this critical variable within exposure through ingestion. As a result, the quantification of AOX in samples relevant for children's exposure (e.g. dust and consumer products) and children's urine will provide a first overview of their exposure to novel AOXs in Flanders. The developed approaches can be used in upcoming European biomonitoring programs, e.g., PARC, to assess exposure to AOXs on a larger scale.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Roggeman Maarten

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Alcohol abuse is a major cause of liver disease worldwide. Despite the high prevalence of alcoholic liver disease (ALD), there is currently a lack of sensitive and specific early biomarkers, resulting in diagnosis at late (irreversible) stages of disease progression. Hair has considerable potential as a new, promising matrix to diagnose ALD early. Segmental hair analysis is based on its growth rate (a length of 1 cm corresponds to ± 1-month growth), constituting a promising method to retrospectively assess biomarkers levels over extended periods (weeks to months). This PhD project aims to explore the applicability of hair as a complementary matrix to identify and monitor early-stage biomarkers of ALD. For this approach, a multiplatform untargeted metabolomics workflow, including a unique analytical platform (liquid chromatography-ion mobility spectrometry-quadrupole time-of-flight mass spectrometry), will be employed. Furthermore, several steps will be undertaken to establish fundamental knowledge on human hair's position and utility as a diagnostic matrix, 1) the global composition of hair metabolome and lipidome will be elucidated, and 2) the relationship between the hair and plasma metabolome and lipidome will be investigated. The results of this project will improve our understanding of the position of hair as a diagnostic matrix in chronic (liver) diseases, and the identified ALD biomarkers have the potential to assist disease management in the early disease stage.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: van de Lavoir Maria

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Metabolomics is the holistic study of endogenous metabolites (lipids, amino acids, sugars, small polar organic acids) and their function within cells, tissues, or organisms. Metabolomics may detect low, but critical effects that are not observed by conventional toxicological methods following exposure to external factors. Exposure to chemical compounds, even at trace levels, may indeed cause measurable changes and biochemical alterations for a given physiological state. To investigate these changes in humans, metabolomics is ideally performed in blood (i.e., plasma, serum) and/or urine. To cover the vast array of metabolites, the Toxicological Centre (TC) of the University of Antwerp has developed in-house untargeted metabolomics and lipidomics analytical platforms based on liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS) for the analysis of different biological matrices, such as cell extracts and animal tissues1-3. However, there is an urgent need to evaluate and refine these platforms for the analysis of human biological fluids, such as blood and urine. The methods used for human biological fluids may differ from those used for cells and tissues due to a higher complexity and different abundances of various metabolites. The general objective of the Postdoc Challenge at the TC is to attract a post-doctoral researcher with expertise in the sample preparation, data acquisition and data processing for untargeted metabolomics and lipidomics in human biological samples. Specific objectives are: - To develop and optimize sample preparation procedures for blood and urine to ensure a wide coverage of endogenous metabolites in these complex matrices - To tailor the current untargeted metabolomics and lipidomics platforms based on LC-QTOFMS for the specific needs and characteristics of these matrices - To investigate the usefulness of including additional separation dimensions, such LCxLC or ion mobility in the acquisition of data of higher quality - To refine the current data processing and metabolite annotation workflows using vendor and open access software tools for the specific needs of human metabolome and lipidome - To propose a set of QA/QC measures and criteria for the data acquisition and data analysis workflows to ensure the production of high-quality data. The outcome of this project would be to establish the first untargeted metabolomics/lipidomics platform at UAntwerpen for human biological samples. A high quality and high-end metabolomics platform using state-of-the-art technology and bioinformatics is crucial in order to obtain reliable data which can be used in clinical and biological fields. The applicability potential of such platform is large with direct application in life sciences for the discovery of effect biomarkers associated with a wide variety of diseases (chronic inflammation, metabolic disorders, liver diseases, etc.), but also possibly linked to exposure to chemicals present in our daily life.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

DNA adducts provide information on the exposure and biological effects of chemical hazards. Hence, the birth of DNA adductomics has not gone unnoticed in the era of exposomics, in which the aim is to study the whole of environmental exposures and biological consequences thereof. This project will apply DNA adductomics in large-scale exposomics for the very first time, to further unravel the determinants of food allergy and esophageal cancer. Firstly, this project aims to lay the foundation for DNA adductomics data preprocessing. The second and third aim are to study differences in DNA adduct formation in food allergy and esophageal cancer cases versus controls. Observed shifts in the DNA adductome will be linked to exposure to environmental pollutants, as assessed in children with food allergy in the ENVIRONAGE cohort in Flanders (n > 400), and to (multiple) mycotoxin exposure(s) in adults with esophageal cancer in an IARC/WHO sub-Saharan esophageal cancer cohort (n > 300) using state-of-the-art multivariate and machine-learning based modelling. Results will be explored mechanistically using in vitro digestions and/or in vivo rodent or zebrafish experiments, to increase knowledge on the molecular underpinnings of environmental exposures in relation to food allergy and esophageal cancer and infer causality to proposed determinants. Furthermore, this project will pave the way towards scientific independence and the very first dedicated DNA adductomics research line in Europe.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

INQUIRE aims to protect citizen health by providing knowledge, tools, and measures to substantially improve indoor air quality (IAQ). We will conduct research and evaluate innovative actions to reduce hazardous chemical and biological determinants in homes, positively impacting the health of residents. INQUIRE will focus particularly on infants and young children (<5 years old) as highly sensitive groups that spend a substantial time in the home environment. INQUIRE will comprehensively advance our understanding of the determinants of IAQ in homes by implementing innovative, low-cost, non-invasive sampling strategies (sensors, indoor/outdoor passive sampling, urine biomonitoring) to characterize determinants of household IAQ and their importance to human exposure. To capture the breath of IAQ determinants across Europe, the study will monitor for one month over 200 homes distributed across 8 countries, covering a gradient of conditions in each country. Tiered high-resolution chemical and biological screening techniques and wide-scope holistic characterisation of hazards will provide a comprehensive assessment of the determinants of IAQ. Multifaceted data analysis techniques (including machine learning, exposure modelling, geospatial analysis), will link chemical, biological and toxicity profiles with drivers of IAQ to identify sources and prioritize pollutants. Source identification will feed directly into the testing of both novel technologies and readily deployable strategies to improve IAQ, resulting in evidence-based recommendations and a draft of policy strategy for developing IAQ standards. INQUIREs Open Science approach and generated FAIR data on hazardous determinants, their effects, risk factors and sources will endorse continuous exploitation of results. Open dissemination of generated knowledge will raise citizen awareness while exploitation by industry and policy makers will endorse a transition towards homes with zero pollution. The project INQUIRE is part of the European cluster on indoor air quality and health (name and acronym to be decided).

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Poma Giulia

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Volatile and semivolatile chemicals are recognised as byproducts of disease, boosting volatile analysis as paramount instrument to monitor health and disease, personalize health care and objectively establish the effect of different treatment strategies. Next to volatile organic compounds (VOCs), semivolatile compounds (SVOCS) are present in the environment and in biological matrices, but most of them need to be chemically and structurally identified and their role in health and disease is yet to be explored. In this proposal, we describe the set-up of a highend GCxGC-QTOF-MS facility for analysis of VOCs and SVOCs in biological samples like breath, blood, urine, faeces of humans and animals, and in the headspace of cells. The goal is to set up an infrastructure that allows to assess and investigate multiple biological sample types and their headspace for monitoring health and disease, to identify disease biomarkers, to intensify research on the environmental health issues of modern life, and to tackle the hurdles presently encountered in the metabolomics analysis of steroids and small organic acids. By this means, we intend to team up and complement with international volatomics research groups. In Flanders, such a specialised facility is lacking, and will be unique. It combines high sensitivity, ultralow detection limits for analysis and validation of the molecular composition of biological and headspace samples, with specific sampling devices and advanced data processing.

Researcher(s)

• Promoter: De Winter Benedicte
• Co-promoter: Covaci Adrian
• Co-promoter: Lamote Kevin
• Co-promoter: Lapperre Therese
• Co-promoter: Laukens Kris
• Co-promoter: Samson Roeland
• Co-promoter: van Meerbeeck Jan
• Co-promoter: van Nuijs Alexander
• Co-promoter: Wouters An

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

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

The purpose of this project is to perform a systematic survey of the objects in the collection of the Africa Museum (Tervuren, Brussels) for the presence of inorganic and organic toxic substances. This information will be highly relevant for the museum with the aim of handling and preserving their collection in an optimal and sustainable manner.

Researcher(s)

• Promoter: Janssens Koen
• Co-promoter: Covaci Adrian
• Fellow: Alvarez Martin Alba

Research team(s)

• Antwerp X-ray Imaging and Spectroscopy (AXIS)

Project type(s)

• Research Project

Abstract

Halogenated organic pollutants (HOPs) released into the environment may cause adverse effects on the human health. To assess the human exposure risk of HOPs, it is thus necessary to investigate their environmental levels and consider the multiple exposure pathways of people in high-risk areas. Non-target screening (NTS) analytical approaches allow the early detection of potentially harmful novel HOPs. In addition, some novel HOPs may cause remarkable changes in cell metabolites, although they do not exhibit significant dose-effect relationships. Metabolomics may detect low, but critical effects that are not observed by conventional toxicological methods. The application of NTS and metabolomics on sensitive populations (e.g. pregnant women) in the vicinity of halogenated chemical industrial parks would thus provide a screening of high-risk HOPs. Through the cooperation of the Belgian and Chinese teams in this project, we aim at 1) identifying novel HOPs in multiple environmental media relevant for human exposure in the vicinity of chemical industry parks, 2) clarifying the dominant exposure pathways of novel HOPs through the comparison of exposure levels and characteristics of human internal and external exposure, 3) investigating the effects of combined exposure to HOPs on the metabolome of pregnant women, and 4) identifying biomarkers for high-risk HOPs. Altogether, our results will provide the basis for environmental and chemical management of novel HOPs.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Poma Giulia
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Persistent and mobile chemicals (PMs) are man-made and highly polar organic chemicals. Due to potential risks to the environment and humans, policy needs are currently identified. However, there is limited knowledge on PMs, especially on reliable screening and target analytical methods and human exposure pathways. In order to fill knowledge gaps, this research project aims to develop suitable analytical methods using state-of-art mass spectrometric techniques, to screen and prioritize PMs, to explore the occurrence of PMs in environmental matrices relevant for human exposure, and finally to assess the human exposure to PMs. Reliable, sensitive and robust methods using liquid chromatography-ion mobility-high resolution mass spectrometry and liquid chromatography-tandem mass spectrometry will be developed and validated for the screening and quantification of the analytically-challenging PMs. Using these methods, the occurrence and distribution of PMs will then be measured in various environmental samples relevant for human exposure (e.g. dust, fish), consumer products and in human biological samples. Finally, major exposure sources and hazard quotients of PMs will be identified to assess the human exposure to PMs. The outcomes of this research project will further be valuable in establishing policies for the management of human exposure to PMs.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Kim Dahye

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

FoodTraNet is designed to provide high-level training of a new generation of high achieving early stage researchers (ESRs) in a common platform of advanced mass spectrometry tools for food quality, safety and security. Due to the fast growing and changing area in food science researchers need a multidisciplinary, intersectoral grounding in these tools to extract all the potential from traditional and new available methodologies and techniques. Although already available there is still a big gap between research capability and industrial uptake that needs to be bridged to assure their use in more practical and efficient way. The network is designed to bridge this translational gap by creating a multidisciplinary training and research network that will give ESRs the ability to transfer their knowledge from basic sciences to industrial applications. FoodTraNet will cover techniques including stable isotopes, target, suspect, non-target screening and mass spectrometry imaging to obtain the following objectives: 1) identify biomarkers and bioactive compounds to assure food quality and traceability; 2) characterize novel foods to support food safety and security; and 3) developed and characterize new products based on the latest advances in nanotechnology: edible photonic barcodes; nano-sensors; multi-functional polymer nanostructured materials; and new, active and intelligent packaging. These goals will be achieved by a unique combination of "hands-on" research training, non-academic placements/courses and workshops on scientific and complementary transferrable skills facilitated by the academicnon- academic composition of the consortium. Strong industry involvement in the project, with full participation of CONCAST and SMEs from different sectors, will provide ESRs with the transferable skills necessary for thriving careers in a burgeoning area that underpins food sustainability through innovative technological development across a range of diverse disciplines.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project website

Project type(s)

• Research Project

Abstract

The human exposome covers the totality of non-genetic exposures from conception throughout the life course. The Flemish exposome project, FLEXiGUT, combines the unique and complementary expertise in Flanders on dietary- and environment-related human biomarkers and biomonitoring, metabolomics, microbiome research and epidemiology to investigate the complex human exposome. This first large-scale Flemish Exposome study, will make use of biomonitoring and -omics based technologies on the available biological matrices of the Flemish Environage Birth and the Flemish Gut Microbiome cohorts. Associations between the acquired exposome metadata and chronic low-grade gut inflammation parameters and related diseases will be analysed using an integrated -omics approach. Our pioneering results will be validated through extension towards other international cohorts.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

- Phthalates (i.e. DEHP) and alternative plasticizers (APs) are used in plastics to increase their elasticity and extend their lifetime. - Leaching of plasticizers from indwelling medical devices used in the neonatal intensive care unit (NICU) might expose neonates to these chemicals at levels far exceeding tolerable daily dose recommendations. - Although awareness of these plasticizers is growing, they are still used in many (most) medical devices even in the NICU. - Premature neonates are extremely vulnerable to external insults. - This project aims to explore the utility of levels of plasticizers and their metabolites in a keratinous non-invasive matrix (hair) and in urine as a diagnostic tool for cumulative and past exposure in the neonatal intensive care unit. - The possibility that this matrix can detect past and cumulative exposure in this vulnerable population is a novel approach and is expected to provide fresh insights into the detection of past exposure to these chemicals. - The studied plasticizers have toxic effects on neuronal and pulmonary cells, as proven in in vitro and in vivo (animal and human) models. - Based on these pathophysiological effects, we hypothesize that exposure to these plasticizers during the NICU stay contributes to the long-lasting impaired (neurocognitive and lung) development that is frequently observed in neonates after discharge from NICU.

Researcher(s)

• Promoter: Jorens Philippe
• Co-promoter: Covaci Adrian
• Co-promoter: Mulder Antonius

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Emerging contaminants (ECs) are a group of anthropogenic chemicals widely distributed in the environment. These chemicals are of growing concern due to their ubiquitous presence in the environment and potential hazardous effect to humans. Thus, it is critical to investigate the levels and patterns of exposure to ECs in the environment/human to provide a better assessment of the health risks. Since people are exposed to a mixture of complex chemicals in the environment, the assessment of personal exposure is the key to link the external and internal exposure and eventually the health effects. Silicone wristband represents the aggregate personal exposure of multiple exposure pathways, which would be ideal to predict the internal exposure. In this study, we will use the silicone wristbands as sampler to monitor the external exposure to ECs on the individual level, quantify the external and internal exposure concentration and then use a refined model to predict the internal exposure concentrations from the silicone wristband exposure data. We will also use suspect screening techniques to explore and identify new ECs using silicone wristbands to aid future exposure studies. This study aims to provide new insights into the exposure levels and patterns, gain better understanding for the correlation between external and internal exposure and refine and develop a method to predict the internal exposure dose thus simplify the exposure assessment in the general population.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Poma Giulia
• Fellow: Yin Shanshan

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Owing to the increasing plastic production, humans are exposed to a rising number of plastic additives. Many of these have been associated with neurotoxicity and adverse effects on the endocrine system. In the past, several new compounds linked to plastics have been identified, which are designated as "contaminants of emerging concern" (CECs). This project aims to identify new CECs derived from plastics. A novel, ultra performant analytical approach based on the hyphenation of liquid chromatography, ion mobility spectrometry and high-resolution mass spectrometry (LC-IM-HRMS) will be used for the creation of a database containing collision cross section (CCS) values of known and new CECs. Non-target and suspect screening approaches will be applied for the identification of new CECs in plastic and indoor dust samples. Using in vitro experiments in hepatic systems, Phase I and II metabolites of the new CECs will be identified. Screening of human urine samples will be conducted to confirm the metabolite's occurrence and identify the most relevant biotransformation products in vivo. Furthermore, a quantitative method using LC-MSMS will be developed and validated. Using this method, a proof-of-concept study on a set of 100 human urine samples will be conducted with the purpose to establish time-trends for these new CECs. The results obtained with this workflow will deepen the knowledge about human exposure to CECs and have an influential input on future biomonitoring programs.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Belova Lidia

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

We will develop a pioneering holistic framework based on innovative approaches to explore the human exposome in terms of exposure leading to adverse effects with a focus on endocrine-modulated neurological and metabolic disorders by: i. Identifying and characterizing the exposure sources of relevant chemicals in the context of the xposome framework; ii. developing and applying in silico, in vitro and in vivo human and animal models to investigate the absorption, distribution, metabolism, and excretion processes after exposure to chemicals; iii. setting up relevant clinical/epidemiological exposure-wide association studies to better understand the associations between exposure and neurological and metabolic disorders in longitudinal and (nested) casecontrol cohorts and including birth cohorts to understand transgenerational mechanisms; iv. using targeted and untargeted omics techniques (e.g. metabolomics and transcriptomics) in human and animal biological systems to aid data-driven discovery of causal factors for adverse health effects; v. linking exposure to mixtures by integrating exposome research with the adverse outcome pathway concept, a novel toxicological framework structuring the cascade of biological events from an initial molecular-level perturbation of a biological system to an adverse health outcome.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Bervoets Lieven
• Co-promoter: Blust Ronny
• Co-promoter: Eens Marcel
• Co-promoter: Jorens Philippe
• Co-promoter: Knapen Dries
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This budget represents the yearly financial support from the University of Antwerp to our research group (Toxicological Center) for maintenance of the current instrumentations (headspace-GC-FID, GC-MS, GC-MSMS, LC-MSMS, LC-QTOFMS).

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a collaboration project between the Aarhus University and the Toxicological center, involving the analysis of persistent organic pollutants in bones and blubber of dolphins and relating these results to atherosclerosis observed in these animals.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The levels of organophosphorus flame retardants (PFRs) and plasticisers are to be investigated in 51 food samples belonging to 17 food groups purchased in the frame of the most recent Swedish food market basket study. Samples will be analysed in LC-MS/MS.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Persistent and Mobile chemicals (or PMs) are at this moment insufficiently considered in chemical regulation and management. One important group of PM chemicals is the group of per- and polyfluoroalkyl substances (PFAS). In this project, we aim to investigate the identity, occurrence, fate and sources of PMs in order to elucidate the major exposure pathways and to assess the current human exposure to several groups of PM chemicals, including PFAS.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

In this assignment, we want to use non-target screening to find out which substances may be present in indoor dust samples and, based on this, to evaluate their possible effect on health. The assignment consists of 4 different phases: - In phase 1 a selection of indoor environments with possible sources for a wide variety of (new) chemical substances will be made in consultation with the steering committee. - In phase 2, based on this selection, indoor dust samples are collected from all addresses, whereby a sufficient quantity of samples is collected for the possible application of an additional analysis for concentration of certain chemical substances. After appropriate sample preparation, a non-target / suspect screening is first performed on the samples obtained. - In phase 3, the identified chemicals are evaluated for possible effects on human health. If necessary and possible, in this phase, a re-analysis of the collected dust samples is carried out, in which the concentrations of the most important chemicals found are determined semi-quantitatively (this is after all important for both the effect on health and an estimation of sources). - Based on the results obtained, in phase 4 a sampling and analysis strategy will be drawn up in function of human biomonitoring, taking into account the results of the non-target screening and the effective concentration determinations.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease. Despite the high prevalence of ALD, diagnosis and disease staging are still missing sensitive and specific biomarkers. As a result, most patients are diagnosed only at an advanced stage, leading to frequent hospitalization, increased medication use and liver transplantations, a high-burden option for patients and health-care systems. This PhD project (METABOLHAIR) aims to explore the applicability of human hair as a new diagnostic matrix in metabolomics to identify and detect early-stage biomarkers of chronic ALD. This project strives to elucidate the global hair metabolome composition, its inter-individual variations and possible influencing parameters. Identification of ALD biomarkers will be performed using an advanced metabolomics workflow, including a unique analytical platform (two-dimensional liquid chromatography-ion mobility spectrometry-quadrupole time-of-flight mass spectrometry). Furthermore, the applicability of the biomarkers in segmental hair analysis to predict disease progression and diagnose the different stages (alcoholic fatty liver disease and alcoholic steatohepatitis) of ALD will be investigated. The METABOLHAIR project will help improve the current knowledge on the hair metabolome and can be used to screen individuals with alcohol use disorders for ALD to prevent the development of end-stage liver diseases.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: van de Lavoir Maria

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Within the indoor environment, humans are exposed to a diverse group of contaminants of emerging concern (CECs), who remain largely understudied. Two groups of ubiquitous CECs, namely the high molecular weight phenolic antioxidants (HMW SPA) and the organic phosphite antioxidants (OPA), have received little attention in literature. These novel antioxidants exposure has only been accessed in Asia and North-America by applying methods that focus on a small subset of novel antioxidants (AOXs). Therefore, the goal of this project is to develop both qualitative and quantitative exposure methods, including a human biomonitoring method for novel AOXs metabolites. These innovative methods will be applied in Flanders, providing the first exposure studies in Europe for the novel AOXs. This goal will be achieved by employing state of the art mass spectrometry (MS) equipment coupled to liquid or gas chromatography. By developing target and non-target MS screening methods and applying novel techniques such as iterative MS within the screening methods. This project will result in the first biomonitoring method of novel AOX metabolites accessing human exposure in Flanders. The developed methods can be used in upcoming European biomonitoring programs, accessing exposure on a larger scale. In conclusion, this project will be of great added value as it will be the first in Europe to access human exposure to novel antioxidants by employing innovative techniques.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Roggeman Maarten

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

An important issue encountered in the historical artworks is the fading of the original colors because of their strong light sensitivity, infamously leading to the discoloration of masterworks even within an artist's lifetime. This phenomenon is clearly evidenced in many paintings of 19th century European impressionist artists, such as van Gogh, in particular when Organic Red Pigments (ORP) have been used. The identification of these ORP in historical paintings remains a main challenge because of (1) the generally low concentration of the original pigment remaining after an aging period of ca. 100 years, (2) the scarcity of the paint micro samples available for analysis and the difficulty of obtaining additional ones and (3) the complexity of degradation behavior in the presence of oxygen, inorganic semiconductor pigments, binding media or varnish. The objective of the RED-OPEN project is to develop a multi-analytical approach based on mass spectrometry and spectroscopic techniques (A) to understand their discoloration mechanism and (B) to identify their breakdown products, even if the original molecules are no longer present in the artworks. The successful completion of RED-OPEN will have a major impact in the understanding of the original artwork's appearance and will provide comprehensive and detailed knowledge of the progressive changes throughout the painting's history. RED-OPEN will generate knowledge that will help conservators and conservation scientists to understand the causes of discoloration and formulate mitigating actions, preserving invaluable art for future generations and further proposing a digital reconstruction of its originally intended appearance.

Researcher(s)

• Promoter: Janssens Koen
• Co-promoter: Covaci Adrian
• Fellow: Alvarez Martin Alba

Research team(s)

• Antwerp X-ray Imaging and Spectroscopy (AXIS)

Project type(s)

• Research Project

Abstract

This project aims to utilise the Australian Census 2021, a unique opportunity to link exposure to chemical and biological hazards with catchment socio-demographic data via systematic wastewater analysis. The project is expected to advance our capabilities to identify emerging hazards and understand factors that affect spatiotemporal trends in hazards across Australia. Moreover, in a world first, the project aims to assess chemical fate on a national level by linking sales/use with fate and release from wastewater treatment plants and assess treatment efficiency at >100 plants around Australia. The project expects to provide insight for government, wastewater managers and industry into hazards that may affect environmental and human health.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The specific project to be developed at UA aims at identifying emerging chemicals in novel food items for human and animal consumption (including edible insects, farmed fish, insect-fed fish, beehive products, and dairy products) using non-target and suspect screening based methods. Year 1. At first, suitable workflows for non-target and suspect screening methodologies based on liquid chromatography and high-resolution mass spectrometry (LC-HRMS) will be developed and harmonized for the identification of emerging chemicals present in the selected food. Such methods are currently in full development for human biological samples (urine and serum), and it is expected that they could serve as basis for the methods to be developed in food. In case of non-target methods, data analysis will be carried out without any a priori defined suspects, while for suspect screening methods a comprehensive list of emerging chemicals that are suspected/expected to be present in the analyzed samples (e.g. emerging pesticides, per- and polyfluoroalkyl substances, chlorinated paraffins, new plasticizers, etc.) will be set up. Then a selection of relevant samples (e.g. n=3 per food category) belonging to each novel food category will be purchased and analyzed. Year 2. Once the results of this first screening will be available, the dataset of samples belonging to the above-mentioned novel food categories will be widened (to n=10 per food category) and analyzed using the optimized methods. The performance of such analytical platforms and the generated results will then be critically assessed by chemometric data processing (combining multivariate analysis – like principal component analysis (PCA), random forest classification and support vector machines – with the application of univariate tests). The results of the statistical analysis will be combined with available information about food production, in order to establish differences and similarities in the patterns of emerging chemicals in novel food items. This information will be also transferred to the European Food Safety Authority (EFSA) to assess the necessity of including these emerging chemicals in regular monitoring schemes. The outcomes of this project will contribute to a preliminary food safety assessment of the potential of such matrices to be used as alternative food sources. Additionally, this specific project will offer insights on the most "promising" novel food categories present on the Belgian market to favor. In parallel, the EU ETN proposal FoodTraNet will be re-submitted and the coordinator of FoodTraNet, Dr. Nives Ogrinc has supplied a letter of support stating this engagement. As such, this proof of concept of contamination with emerging chemicals will be able to increase the chances of success of the resubmitted proposal and will be able to extent the investigation at broader European level.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a contract between the Endocrine Society and the University of Antwerp for the analysis of organophosphate flame retardants in urine samples. These results will be used to investigate the current contamination status of highly-ranked EU persons to these contaminants.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a contract between the University of Antwerp and Hokkaido University for the analysis of organophosphate flame retardants in urine samples collected from the Japanese children. These results will be used to investigate associations with the children exposure to these contaminants.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a service contract between the University of Antwerp and Griffiths University (Australia) for the analysis of organohalogenated contaminants, such as POPs, BFRs, and their metabolites in tissue samples from marine animals

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a contract between the University of Antwerp and VITO for the analysis of organophosphate flame retardants, phthalates and alternative plasticizers in Democophes urine samples. These results will be used to investigate associations with the past children exposure to these contaminants.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Globally, coastal ecosystems are undergoing rapid changes with respect to habitat degradation and pollution, which is especially true along the East Asian coastline due to rapid industrial and urban development. This has led to effects on coastal wetlands in terms of biodiversity and also on the quality of the stopover sites for migrating birds, such as shorebirds. Shorebird populations are declining at an alarming rate along the East Asian Australasian flyway (EAAF), the reasons for which are currently unknown. The role of pollution in these declines, which is unknown, is suspected to play a role. One way that pollutants might decrease survival during migration may be via immunomodulative properties that can affect the susceptibility to disease. Pollution has indeed been related to the outbreaks of disease and increase in disease as early as the 1960s in animals, including birds, and humans. In this study, we aim to study the impact of pollution on the biodiversity of littoral macroinvertebrates in coastal wetlands in East Asia, and the resulting combined impact of food availability, pollution and disease on migrating shorebirds using these wetlands as stop-over sites. The potential combined impact of pollution and resultant disease on the fitness and decline of shorebirds has been neglected until now. The proposed project will pioneer investigations into the combined impact of pollution and disease on the decline of migratory shorebirds along the EAAF, with a specific focus on pollution picked up along the Chinese coastline during migration. As there is no information on the impact of pollution (in combination with other stressors e.g. lack of food, disease and high energetic demands during migration) on migratory shorebirds along the EAAF, nor in other flyways (e.g. the East-Atlantic Flyway), the results of the project will bring scientific renewal and will inform conservation and risk management measures for important stop-over ecosystems

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The present project aims at developing innovative analytical and sampling approaches to estimate the (ab)use of illicit drugs and psychoactive pharmaceuticals, e.g. antidepressants, antipsychotics, benzodiazepines, and opioids in the general population. The analysis of human excretion products of substance use in wastewater has the unique properties to deliver such data. The overarching objective is to validate innovative active-passive sampling (APS) and detection strategies for biomarkers of illicit drugs and psychoactive pharmaceuticals to be used for the long-term monitoring of substance use in communities. The hypothesis to be tested is if APS will provide a more convenient sampling strategy compared to daily 24-h composite sampling. We will first develop analytical assays to measure biomarkers of psychoactive pharmaceuticals and drugs in wastewater. Then we will develop APS strategies for the target analytes in influent and effluent wastewater and will investigate the advantages/limitations of the APS strategies in real-life conditions. These new sampling strategies will be compared to the conventional 24-h composite sampling. We will plan sampling campaigns in 5 Slovene and 3 Belgian cities to: estimate for the first time community-wide psychoactive substance use in the Slovene and Belgian cities; evaluate chemical removal efficiencies for the wastewater treatment plants; investigate the utility of APS for improved identification of new psychoactive substances.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Blust Ronny
• Co-promoter: Town Raewyn
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Alcohol abuse is a major cause of liver disease worldwide and is the most common cause of acute-on-chronic liver failure. Despite the high prevalence of alcohol-associated liver disease (AALD), there is currently a lack of sensitive and specific early biomarkers, resulting in diagnosis at late (irreversible) stages of disease progression. The objective of this research project is the identification of (a panel of) small-molecule biomarkers to diagnose early stages of AALD through an advanced metabolomics workflow. Identification of mechanistic biomarkers for AALD will be performed in an in vitro experimental setup, using HepaRG® liver cells exposed to ethanol. A unique and ultra-performant analytical system (two dimensional liquid chromatography-ion mobility spectrometry-quadrupole time-of-flight mass spectrometry) will be used to identify possible biomarkers. An in vivo proof-of-concept study will be performed to extrapolate the applicability of the in vitro identified biomarkers to an in vivo situation. For this purpose, plasma and liver tissue samples of patients suffering from alcoholic fatty liver disease and steatohepatitis, will be investigated. Obtained data will help to improve the current knowledge on the mechanisms of action of alcohol-induced hepatoxicity and to provide new input for adverse outcome pathways. The results of this research project can be used as a lead for a clinical cohort-study to diagnose different stages of AALD.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Iturrospe Elias

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

- Premature neonates are extremely vulnerable to external insults. - Bisphenol A and phthalates (DEHP) are plasticizers, used in soft plastics to increase their elasticity and extend their lifetime. - Leaching of plasticizers from indwelling medical devices used in the neonatal intensive care unit (NICU) might expose neonates to these chemicals at levels far exceeding tolerable daily dose recommendations. - Although awareness of these plasticizers is growing, they are still used in many medical devices in NICU. They are prohibited in the production of toys intended for children under 3 years of age, but legislation about their use in medical devices isn't strict or clear. - The studied plasticizers have toxic effects on neuronal and pulmonary cells, as proven in in vitro and in vivo (animal and human) models. - This project aims to explore the utility of plasticizer levels in an emerging non-invasive matrix (hair) as a diagnostic tool for cumulative and past exposure in the neonatal intensive care unit. - The possibility that this matrix can detect past exposure in this vulnerable population is a novel approach and is expected to provide fresh insights into the detection of past exposure to chemicals. - Based on these pathophysiological effects, we hypothesize that exposure to these plasticizers during the NICU stay contributes to the long-lasting impaired (neurocognitive and lung) development that is frequently observed in neonates after discharge from NICU.

Researcher(s)

• Promoter: Jorens Philippe
• Co-promoter: Covaci Adrian
• Co-promoter: Mulder Antonius
• Co-promoter: Verhulst Stijn
• Fellow: Panneel Lucas

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Wastewater-based epidemiology (WBE) is now an established approach that is used to monitor the consumption of a selection of illicit drugs. However, WBE can also become a valuable source of information about new drug-related threats such as consumption of new psychoactive substances (NPS), licit and illicit opioids, as well as new trends in drug use (e.g., crack cocaine and cannabis). The goal of EuSeME is to further develop WBE as an early warning system to monitor emerging drug problems across Europe. First, qualitative and quantitative information about the consumption of NPS and opioids across Europe will be obtained through the development of analytical methods and retrospective analysis of wastewater and urine samples. Second, a thorough literature review will be carried out to identify additional relevant biomarkers of crack cocaine use. Analytical methods will be developed and integrated with existing ones to include these new biomarkers and monitor consumption of crack cocaine through WBE. Third, a thorough investigation of the sorption of cannabis biomarkers on suspended matter present in wastewater will be carried out. Outcomes will be used to establish a detailed protocol, providing a robust and harmonised approach to monitor consumption of cannabis through WBE. Finally, two broad sampling campaigns aiming at covering all of Europe will be carried out, focussing on the newly identified biomarkers and on conventional drugs. These campaigns will provide unique insights about emerging threats linked to the use of NPS, opioids, crack cocaine and cannabis, as well as an updated view about the situation of consumption of conventional illicit drugs in Europe. By implementing a practical application of drug-related research, EuSeME seeks to provide support to the activities of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), national governments and stakeholders, law enforcement, as well as national focal points.

Researcher(s)

• Promoter: van Nuijs Alexander
• Co-promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Chlorinated paraffins (CPs) are a complex mixture of thousands of individual compounds which have been used as plasticizers, flame retardants and additives to various lubricants, adhesives and metal working fluids. Certain CPs are recognised as potential carcinogens and have exhibited toxic and bioaccumulative properties, culminating in restriction of their use due to their registration as Persistent Organic Pollutants (POPs) under the Stockholm Convention in 2017. As semi-volatile compounds, CPs may be released from consumer products and materials via volatilisation or leaching and tend to bind strongly to particulates, such as indoor dust. Inadvertent ingestion of contaminated dust is considered to be a major pathway of human exposure to CPs. This study aims to a) investigate the current human exposure risks posed by CPs in the indoor environments of Belgium and b) explore the transport and fate of such chemicals. Sensitive, reliable and robust methods for the quantitation of CPs will first be developed and validated using state-of-the-art techniques based on advanced mass spectrometry. The occurrence and distribution of CPs will then be assessed in dust from a range of indoor microenvironments to produce an estimate of human exposure via incidental dust ingestion for the Belgian population. Finally, the distribution of CPs in consumer goods and the migration of CPs to dust will be investigated to aid in mitigating harmful effects to human populations in the future.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Poma Giulia
• Co-promoter: van Nuijs Alexander
• Fellow: McGrath Thomas

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a contract between the University of Antwerp and Hokkaido University for the analysis of organophosphate flame retardants in urine samples collected from the Japanese children. These results will be used to investigate associations with the children exposure to these contaminants.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Chlorinated paraffins (CPs), also known as polychlorinated n-alkanes with chlorine degree ranging from 30% to 70% by mass, are a complex mixture of thousands of isomers, diastereomers, and enantiomers.[3] They can be divided into short (SCCPs, C10-C13), medium (MCCPs, C14-17), and long chain CPs (LCCPs, > C17) according to their carbon chain length.[4] Among all CP groups, SCCPs have the highest toxic potential.[5] Although it has been suggested that ~ 85% of the human exposure to SCCPs occurs via the diet, concentration data of SCCPs in food is scarce. This is mainly caused by the complexity of CP mixtures, resulting in an unprecedented analytical challenge. In this project proposal, an adequate analytical method based on GC-MS/MS for the analysis of SCCPs in a wide variety of foods will be developed, validated and applied to evaluate the exposure of the Belgian population to SCCPs. First, a representative sampling plan will be developed by combining foods with expected contamination with SCCPs and foods that are highly consumed and thus have a significant impact on the dietary exposure. Next, the validated analytical method will be applied to the analysis of 220 food samples. Afterwards, the congener patterns of the highly contaminated samples (max 20 samples) will be further identified using High Resolution Mass Spectrometry. Since it has already been demonstrated that SCCPs can be released from hand blenders and household baking ovens, the impact of the use of food contact materials on the contamination of food and on the exposure will be further investigated. Finally, all data will be combined, and an exposure assessment will be conducted. Based on the results generated during the project, it can be evaluated whether control measures at (inter)national level need to be taken.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Environmental remediation for safeguarding human health is difficult. Effective processes enabling scalable operability are lacking. triboREMEDY aims at solving this impasse by providing the foundational steps towards the novel technology called "tribolysis" for safe, controlled, and efficient degradation of hazardous chemicals and effective inactivation of the pathogens. The scientific and technological breakthrough of triboREMEDY is based on the generation of nascent surfaces, high pressures, and shearing forces that will supply the required activation energy for dissociation of polychlorinated biphenyls (PCBs) and cell disintegration of pathogens. The centrepiece of triboREMEDY is the fully-controlled "triboreactor" in which mechanically (tribologically) induced chemical reactions take place as viable alternative to A) highly costly incineration or storage of hazardous waste, notably PCBs, and B) chemical, thermal inactivation or ultra-violet irradiation of pathogens in drinking water. The main project aim is to set scalable design rules for the "triboreactor" (proof of concept) based on the identification of PCB degradation products and pathogen inactivation pathways together with their relationships to operational parameters. In addition to this, the long-term vision beyond halogen elimination of PCBs and disinfection of drinking water avoiding chlorine treatments, will cover other toxic organic chemicals, application in chemical synthesis, catalysis free of critical raw materials, coating processes, requiring sensors for the monitoring of trace components, opening a wide new scientific and technological field. triboREMEDY will be driven by a multidisciplinary team of excellent researchers in mechanical engineering, chemistry, physics, biology, and medicine enabling the required unique breakthrough and interdisciplinary approach.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Black Soldier Fly Larvae (BSFL) are larvae from the insect the black soldier fly. They are currently being reared on a global industrial scale as a feed ingredient. They can be reared on a wide range of side and waste streams from food industry and agriculture, being converters of these streams into valuable biomass. Given the struggle of our food system to sustainably meet the protein demands of the growing world population, BSFL rearing offers an innovative, bio-based alternative contributing to a circular economy. As insect production is a novel branch of livestock production, it is up to (academic) researchers to gather the same level of in-depth knowledge that is available for other farm animals on production safety and optimization. For example, the impact of the chemical and microbial composition of the feed on the zootechnical performance and on the microbial safety of BSFL is virtually unknown. Furthermore, preliminary research points towards high value applications for other industrial sectors, such as the pharma and waste treatment sector, that could generate more profit for the insect production sector. This project aims to generate more fundamental knowledge that could support the insect sector, legislation and the co-emerging food value chain to remove legislative and technical hurdles in rearing and valorisation. More specifically, we will explore the hardly investigated interaction between the BSFL, their substrate and their gut microbiota. Such interactions are expected to depend on the substrate and affect (i) the growth of the larvae, (ii) their microbial safety, and (iii) their chemical safety. The overall goal of this project is to define and characterize a set of microorganisms that can be used to manipulate the gut microbiota of BSFL in order to boost its performance in each of the three aforementioned domains and increase their economic value.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

In recent times, the use of opioids has escalated drastically and resulted in a crisis of epidemic proportions in North America. In Europe, the use of opioids has also increased, but in smaller proportions compared to North America. However, the extent to which opioids are (mis)used in Europe needs to be further explored. In this project, we will optimise and develop a highthroughput bioanalytical assay based on μSPE-LC-MS/MS capable of measuring a broad range of biomarkers of opioids use in the ng/L range in wastewater. We aim at obtaining near real-time, objective and complementary information on the use of opioids at high spatio-temporal resolution through a wastewater sampling campaign in different locations in Belgium. By generating highly relevant data on the consumption of opioids together with triangulation of this data with other existing datasets (e.g. Farmanet, Health Interview Survey,...), this project can aid in obtaining a better picture on the opioid use in Belgium which is of importance for policy makers in optimizing and evaluating prevention, treatment and harm-reduction strategies on the subject of pain management. Furthermore, by combining multiple datasets, information on the illegal use of opioids can be obtained. In a last step, the obtained data will be correlated with existing socioeconomicco-variates of the investigated communities to obtain a better insight on the relationship between socio-demographic features, and prevalence of use of opioids.

Researcher(s)

• Promoter: van Nuijs Alexander
• Co-promoter: Covaci Adrian
• Co-promoter: De Loof Hans
• Fellow: Boogaerts Tim

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Water monitoring programs are largely used to assess the quality of aquatic ecosystems and verify compliance with environmental quality standards. However, the use of inadequate tools for the assessment of the impact of pollutants to aquatic organisms often results in inaccurate evaluations of ecological risk. Current approaches either rely on the total concentration of a pollutant, which has shown to be a poor predictor of ecological risk, or make large use of organisms for biological testing. This proposal aims to create and test a new generation of monitoring devices capable of measuring the fraction of pollutants present in the water that is relevant for ecological risk assessment, that is, the fraction of pollutants effectively available for assimilation in the organism and thus most likely to cause toxicity. An interdisciplinary approach combining biological testing and chemical speciation measurements will be used to investigate mechanistic links between the uptake of organisms and devices and test the performance of the envisaged technology. The automated device will be practical to transport and use on site, and will be equipped with chemical sensors suitable for measuring a wide range of pollutants (e.g. metals and organic compounds). This will significantly reduce costs related to field work operations and laboratory analyses and contribute to more robust and reliable water quality assessments.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Fellow: Amato Elvio

Research team(s)

Project type(s)

• Research Project

Abstract

Chemicals are typically used in various products because of their beneficial properties, e.g. flame retardants, plasticizers, etc. However, most of them leach into the indoor environment and may provoke health disorders (e.g. endocrine disruption). With this proposal, we aim to enrich the fundamental knowledge related to new chemicals of concern by studying their occurrence in the indoor environment. Furthermore, we will characterize their biotransformation in humans by in vitro experiments with human liver subcellular fractions. We will then assess for the first time the resulting human exposure to these new chemical entities by investigating human biological samples (urine and handwipes) for the presence of these chemicals and their biotransformation products. Resultingly, we will propose a range of new biomarkers of exposure to be used in future biomonitoring studies. The detection of the newly identified chemicals (and/or their metabolites) in human biological samples will confirm occurred exposure and will assist in the prioritization for further investigation of other aspects, such as toxicity and possible health effects.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Poma Giulia
• Fellow: Christia Christina

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a service contract between the University of antwerp and Griffiths Univbersity (Australia) for the analysis of organohalogenated contaminants, such as POPs, BFRs, and their metabolites in tissue samples from marine animals.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The requested infrastructure (comprehensive liquid chromatograph-ion mobility-quadrupole time of flight mass spectrometer LCxLC-IM-QTOFMS) combines several state-of-the-art technologies into one platform which aims at bringing metabolomics research to the next level. As such, the infrastructure will deliver a combined five-dimension separation and detection technology, the first of its kind in Belgium. This instrument will be dedicated to metabolomics research, the science of endogenous metabolites in cells, tissues or organisms. The infrastructure will be able to optimally separate, detect and identify the very broad and complex chemical space of metabolites ranging from very polar (e.g. amino acids) to non-polar (e.g. lipids and hormones) at low nanomolar concentration range. Within UA, there is a growing need to combine the currently scattered efforts in metabolomics, an Emerging Frontline Research Domain in the UA research scene. Research ranges from drug discovery (mode of action and pharmacokinetic profiling), biomarker and toxicity studies to advanced data-analysis and systems biology approaches, but a dedicated metabolomics infrastructure to strengthen these studies is currently missing. As such, the investment in a core facility together with the gathering of nine research groups from five departments and two faculties would centralize the metabolomics research. This will position UA as a key player in the academic metabolomics research in the BeNeLux and worldwide.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Augustyns Koen
• Co-promoter: Baggerman Geert
• Co-promoter: Bervoets Lieven
• Co-promoter: De Meester Ingrid
• Co-promoter: De Meyer Guido
• Co-promoter: Hermans Nina
• Co-promoter: Laukens Kris
• Co-promoter: Lemière Filip
• Co-promoter: Maes Louis
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Therefore, the project´s goal is the establishment of a set of specific and reliable biomarkers for measurement of CECs in the human body to assess the Belgium population exposure to mixtures of CECs based on the development of an innovative data-independent acquisition workflow. Accordingly, the project encompasses three main objectives: 1. The development of an innovative data-independent acquisition analytical workflow using advanced high-resolution mass spectrometry (HRMS) that will allow us to identify and prioritize the proper biomarkers of CECs and simplifying the data processing of the big data generated in the HRMS analyses. 2. To evaluate the extent of population exposure to mixtures of CECs in Belgium 3. To create a prioritized list of biomarkers to perform a reliable assessment of human exposure to mixtures of CECs.

Researcher(s)

• Promoter: Covaci Adrian
• Fellow: Caballero Casero Noelia

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project is a collaboration between the University of Antwerp and Aarhus University (Denmark) and aims at measuring a range of legacy and emerging contaminants in biological tissues (organs, feathers, blood) from top predators.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a contract between the University of Antwerp and Hokkaido University for the analysis of organophosphate flame retardants in urine samples collected from the Japanese children. These results will be used to investigate associations with the children exposure to these contaminants.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

In order to comply with the REACH-regulations (Registration Evaluation and Authorization of Chemicals) and to improve animal welfare, a human based in vitro model to investigate the hepatotoxicity of new chemical entities (NCEs) will be developed. The designed model is based on an innovative approach combining in vitro methodology with LC-MS metabolomics, a recent – omics domain that examines alterations in the endogenous metabolic profile of cells and organisms. The basis of our model is the hepatic human HepaRG® cell line, which closely resembles primary hepatocytes in terms of metabolic capacity and toxicological response. In a first phase, the model will be developed by exposing HepaRG cell cultures to well known hepatotoxic compounds, such as acetaminophen, valproic acid, fluoxetine, bosentan and aflatoxine B1; the intracellular profile of the endogenous metabolites will be investigated in an untargeted approach using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-QTOF-MS). Differences between the metabolic profiles of exposed and unexposed cells will be examined using bioinformatics tools in order to identify possible biomarkers characteristic for the multiple hepatotoxic modes of action (MoA). A database containing the reference compounds, their MoAs and the corresponding specific biomarkers will be used in a targeted approach to investigate the hepatotoxic MoA of NCEs, including pharmaceutical and/or industrial compounds.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Laukens Kris
• Fellow: Cuykx Matthias

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

We and our surrounding environment are constantly and increasingly exposed to synthetic chemicals, some of which have been shown to cause adverse biological or toxicological effects. Whilst the toxicity of some chemicals has been recognised, leading to their ban or regulated use, many substitutes, for which toxicity has not yet been fully assessed, are continuously being introduced. Consequently, monitoring human exposure and environmental fate of future/emerging contaminants is crucial. In this regard, wastewater plays a central role. Being, on the one hand, a pooled diluted sample of human urine, its composition can provide valuable information about the types and amounts of contaminants to which humans have been exposed to. On the other hand, it is recognised as one of the main sources of contaminants for the environment. This project aims at mining the chemical information contained in wastewater to obtain valuable geographical and temporal information about the exposure of humans to emerging contaminants, as well as to understand the environmental fate of these compounds. (i) Dedicated analytical methods will be developed to identify human metabolites of targeted emerging contaminants (plasticizers and flame retardants). (ii) Fate of these chemicals during wastewater treatment and their occurrence in wastewater of Flemish cities will be investigated. (iii) The gathered data will then be used to model community-wide exposure to these contaminants.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Been Frederic

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Concentrations of metals (e.g. Cd, Co, Cr, Cu, Ni, Pb Zn) and organic compounds (e.g. pesticides, flame retardants, pharmaceuticals) in aquatic ecosystems have been increasing in the last several decades as a result of urban spread, farming and industrial activities. Water monitoring programs are used to assess the quality of aquatic ecosystems and verify compliance with environmental quality standards. However, the use of inadequate tools for assessing pollutant concentrations in water often result in inaccurate evaluations of ecological risk. Current approaches used for water quality monitoring either measure the total concentration of a pollutant, which has shown to be a poor predictor of ecological risk, or make large use of organisms for biological testing. This proposal aims to create and test the technology required to develop a new generation of monitoring devices capable of measuring the fraction of pollutants present in the water that is relevant for ecological risk assessment, that is, the fraction of pollutants available for assimilation in the organism and that could potentially cause toxicity. This device will be practical to transport and use on site, and will be capable of autonomously measure a wide range of pollutants in water over long periods (from days to weeks). This will significantly reduce costs related to field work operations and laboratory analyses. The new technology will contribute to more robust and reliable water quality assessments.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Fellow: Amato Elvio

Research team(s)

Project type(s)

• Research Project

Abstract

With this proposal, we aim to enrich the fundamental knowledge related to the new chemicals that are present in and may affect the indoor environment and consequently, the resulting human exposure. Chemicals are typically used in various products due to their beneficial properties, e.g. flame retardants, plasticizers, etc. However, most of them leach into the indoor environment and may provoke health disorders (e.g. endocrine disruption). We aim at identifying new chemicals of concern and study their occurrence in the indoor environment. Furthermore, we will characterize their biotransformation in humans by in vitro experiments with human liver subcellular fractions. We will then assess for the first time the resulting human exposure to these chemicals by investigating human biological samples (urine and blood) for the presence of these chemicals or their metabolites. Resultingly, we will propose a range of new biomarkers of exposure to be used in future (biomonitoring) studies. The detection of the newly identified chemicals (and/or their metabolites) in human biological samples will confirm that exposure has occurred and will alert on the imperious investigation of other aspects, such as toxicity and possible health effects.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Van den Eede Nele
• Fellow: Christia Christina

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project proposes to develop novel, inexpensive and portable multisensing devices adapted for the rapid on-site screening of a number of illicit drugs, in saliva, using recent advances in biomimetic materials coupled with electrochemistry.

Researcher(s)

• Promoter: De Wael Karolien
• Co-promoter: Covaci Adrian
• Fellow: Florea Anca

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand Univ. Perpignan. UA provides Univ. Perpignan research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The Baltic ecosystem has undergone drastic changes over the past century due to a combination of anthropogenic and natural stressors. As is often the case, these changes have been most notably documented in charismatic wildlife species, including grey (Halichoerus grypus) and ringed seals (Pusa hispida), white-tailed eagles (Haliaeetus albicilla) and otters (Lutra lutra). The concept of BONUS BALTHEALTH is to provide integrated tools that allow for the assessment of the anthropogenic impacts on the ecological functioning and overall health of the Baltic ecosystem.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Tobacco smoking is the major cause of many chronic diseases, especially cancer. Knowledge on population exposure to tobacco smoking is essential to characterise the population health. National questionnaire surveys are currently the main source of population tobacco smoking. However, surveys have clear limitations due to its dependence on true self-reported usage and representativeness of the whole population. International comparison of surveyed data is also restricted due to different questionnaire formats among nations. An additional approach allowing more objective, efficient and near real-time assessment is necessary to address this important societal issue. Hence, the project APOLLO aims at developing and validating an innovative approach, wastewater-based epidemiology (WBE), for assessing population exposure to tobacco and its related carcinogens in the community. This involves analysis of raw wastewater from targeted communities for tobacco-specific biomarkers of exposure and cancer risk (the tobacco-specific nitrosamines (TSNAs) and their metabolites). The project comprises three main objectives: (1) development and validation of the WBE methodology; (2) evaluation of TSNA and metabolite levels in wastewater from different Belgian communities; (3) assessment of population health from exposure to tobacco-specific carcinogens in Belgium. The completion of the project will advance our knowledge on factual and near-real-time assessment of population exposure to these carcinogens from community to national and international levels using WBE as a standardised approach. This will be also a valuable tool to evaluate the efficacy of intervention actions against tobacco smoking and its related diseases in the population and specific community e.g. prisons, high schools. This project will promote my career prospect with enhanced interdisciplinary network and research mobility in Europe.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Lai Foon Yin

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The overall vision of INTERWASTE is to develop scientific understanding of issues related to environmental contamination with toxic organic chemicals (specifically flame retardants (FRs) and pharmaceutical and personal care products (PPCPs)) arising from their presence in the waste stream. Specific research objectives include: (a) exchange of knowledge of and best practice in methods for rapid and cost-effective identification of waste items containing restricted FRs; (b) developing scientific understanding of environmental contamination due to processing of waste items containing FRs; and (c) furthering understanding of the sources of PPCPs and FRs in the sewerage system.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The European Human Biomonitoring Initiative (EHBMI) will establish and implement an ambitious European Joint Programme (EJP) and will provide policy makers with comparable and validated chemical exposure and health data at EU level. This will be done by integrating and building on previous and ongoing EU initiatives, national HBM programmes and studies (including cohorts, epidemiological studies and health surveys). The project will include harmonising and optimising the practices of national HBM programmes, including sample collection, quality assurance and data management; linking external to internal exposure in order to improve exposure models for risk assessment; developing, validating, and applying exposure and effect biomarkers to improve our understanding of the health risks associated with aggregate exposures; and identifying chemicals of concern through novel methods for the holistic analysis of HBM samples and improving the use of HBM data in assessing exposure to and the risks of chemical mixtures.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The aims of this project are: 1) Conduct a wastewater monitoring exercise utilising a standardized protocol to describe the European illicit stimulant drug market through city level studies. Explore within countries differences in city level wastewater estimates to provide a better understanding of geographical patterns between and within European countries. 2) In a sample of selected cities conduct exploratory pilot studies with the collection of repeat waste water samples over a sufficiently long time period to assess temporal variations in consumption patterns and explore the implications of this for sampling and analysis for routine monitoring purpose. 3) Develop models of drug consumption that incorporate waste water analysis with other data sources (such as drug purity, epidemiology and demographical information) and assess the utility of these for commenting on the following questions: a) understanding better illicit stimulant drug consumption patterns at the community level, b) improving market size estimates c) coherence between estimates derived from different data sources, d) if changes in the illicit stimulant drug market resulting from changing availability, purity or police activities are possible to detect in wastewater analysis. 4) Conduct a review and pilot study in selected cities to assess the possible utility of waste water analysis to report on synthetic drug production

Researcher(s)

• Promoter: van Nuijs Alexander
• Co-promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Objectives The following objectives have been set for this project: 1. To provide an overview of existing information on chemicals found indoors by carrying out a literature search. This review will be mainly based on the ECHA chemicals database, results of ongoing and previous LRI projects, and peer reviewed literature. 2. To carry out sampling and targeted analysis of emerging contaminants in dust and air of schools/daycare centers, homes and offices in various European countries. 3. To conduct non-target screening of the same samples collected under objective 2 to identify additional contaminants and combinations of chemicals. 4. To verify if existing exposure models can be used for the new chemicals found, and propose modifications to the models if needed. LRI Project Proposal Form Page 3 of 29 05/09/2015 5. To compare the measured and modelled data with biomonitoring data from the literature and other projects in which partners are participating.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Whereas amalgam was previously the standard dental restorative material for carious or traumatized teeth, dental composites are nowadays routinely used. Their application is even expected to increase since the WHO has started propagating a general phasing down of the use of amalgam. After a widespread clinical use of more than 25 years, dental composites appear an acceptable biological and functional substitute for amalgam. Yet, their biocompatibility is not yet fully characterized. As resin-based materials do not polymerize completely upon placement in the mouth, unpolymerized components may be released. Several eluates have been reported to exhibit different types of toxic effects, including endocrine-disruptive effects. Especially the release of the endocrine disruptor Bisphenol A (BPA) and related monomers from composites has raised concern. With this translational project, we will focus on the release of endocrine disruptive compounds, including BPA, from dental composites intending to bridge the gap between the current alarming toxicological literature and the seemingly favorable clinical observations. Unique to this project is the inter-university collaboration (KU Leuven – UA – VUB) and our integrated fundamental approach to investigating both chemical and biological activity of leached compounds. This will be investigated multidisciplinarily by in-vitro (analytical and bio-analytical) and in-vivo (biomonitoring) research, focusing on the long term.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Bisphenol-A (BPA) is again at the forefront of research because its restriction has resulted in the use of numerous BPA analogues, e.g., other bisphenols (e.g. BPS and BPF). Whereas BPA is a recognized and rather well studied endocrine disrupting chemical, the other bisphenols have not received sufficient attention until now. Very recent studies have shown that some bisphenols have similar effects to those of BPA and stressed the urgent need to focus on the human health risk assessment of these chemicals. Since bisphenols are used without restriction in various food contact materials (FCMs), they could (easily) migrate in food. Using advanced mass spectrometric-based analytical techniques, we will first characterize the conditions in which bisphenols migrate from FCMs. Then, we will investigate the transformation products (TPs) of bisphenols formed under various stress conditions and the metabolites during in vitro metabolism. The estrogen-like potency of bisphenols and their metabolites/TPs will be tested in vitro. A significant contribution of the project will be the validation of multi-residue methods for the determination of bisphenols and their metabolites/TPs in human urine. These methods could be implemented in public health institutes and employed for monitoring the resulting human exposure. The completion of this unique and innovative project will greatly contribute to knowledge on human exposure and potential risks for public health to these BPA-related chemicals. This PhD project is part of a collaborative project with the Jozef Stefan Institute (Slovenia) funded by the FWO.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The Department of Environmental Sciences at Jožef Stefan Institute has invested in new state-of-the-the-art mass spectrometry instrumentation and related laboratory infrastructure, an important and essential technique in modern science, but must now bolster its knowledge capacity and raise its research profile through taking practical steps in training and knowledge transfer and networking activities. The project has been designed to further stimulate cooperation and develop long-term strategic partnerships with five research institutes of excellence from five different European countries by establishing a community of practice in advanced mass spectrometric and related techniques applied to three transdisciplinary thematic pillars: Environment, Health and Food with focus on organic contaminants, element speciation, traditional and non-traditional stable isotopes, nanoparticles and food safety, traceability and authenticity. MASSTWIN has planned management visits, short-term and long-term exchanges of early-stage and senior researchers, thematic scientific workshops/meetings, common working groups and trainings, participation at conferences, trade fairs and open days. MASSTWIN has also been aligned with the objectives of the national Smart Specialization Strategy with an aim to increase science and technology capacity of the JSI-O2. Extensive dissemination/exploitation/communication activities will be aligned with the existing ERAChair ISOFOOD project for Isotope Techniques in Food Quality, Safety and Traceability, coordinated by JSI-O2. The MASSTWIN Users group will consist of representatives of higher education, the JSI Technology Transfer Centre, industry, governmental bodies, NGO's, and wider community through outreach activities and will therefore account for a positive impact not only on involved personnel and their knowledge, but also on institute level and create positive societal and economical impacts.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Globally, public health agencies face methodological difficulties to efficiently assess the overall health of a community: many of the existing measures (e.g. surveys, hospital records) are very slow, often taking some years prior to reporting, resulting in delayed responses to any changes in the health/disease issues in the community. Thus, adding alternative means to the current measures is highly desirable. This postdoctoral project describes the development and validation of wastewater-based epidemiology (WBE) as an alternative approach to provide comprehensive data on community-wide human lifestyle, diet and health indices, with three key objectives: 1) developing analytical methods to measure specific human health-related biomarkers (e.g. sweeteners for diabetes, cotinine for tobacco use, isoprostanes for oxidative stress) in wastewater; 2) validating the WBE reliability on assessing population health using Belgian communities as a proof-of-concept and prerequisite for its meaningful application across countries; 3) performing an innovative Europe-wide WBE survey to synchronously evaluate community health and examine a model with relationships between the biomarker levels in wastewater and the community health-related indicators. The completion of this project will produce a substantial advancement for a real-time and objective monitoring of community health and will be of immense benefit to intervention designs and policy responses aiming to improve population health.

Researcher(s)

• Promoter: Covaci Adrian
• Fellow: Lai Foon Yin

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed translational research is positioned late in the path from discovery to application, as it will build further on previous mechanistic and epidemiological research. The study rationale builds on evidence from epidemiological studies of much lower exposure to environmental toxicants, on our previous research documenting the legacy of pediatric critical illness and on (unpublished) proof-of-concept studies performed by our group. In a pilot study, concentrations of phthalate (DEHP) metabolites were quantified in plasma collected during PICU stay from children matched for age, type and severity of illness, who were also physically examined and tested for neurocognitive development at 4 year follow-up.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The Toxicological Center will analyze 50 composite food samples collected by the Swedish Food Agency for a list of flame retardants. Toxicological Center takes responsibility for chemical analysis and QA and the SFA takes responsibility for the overall study design and delivery the food samples.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

In recent years increasing amounts of new psychoactive substances (NPS) are detected on the drug market. These substances are chemically based on known illicit drugs (e.g. amphetamine, cannabis), have comparable effects, and are designed specifically to avoid drug regulations. The number of NPS detected keeps rising at a high rate with more than one new NPS reported every week in 2013 in the EU. In most cases, no information whatsoever is available regarding their metabolic aspects, effects, and toxicity, and this has resulted in a significant number of deaths worldwide. Furthermore, solid epidemiological data on the extent of use NPS use is lacking. This project aims at obtaining objective and timely information on the use of NPS in Belgium through a three-tiered approach. In first instance, an evaluation of the Belgian drug market will be made for the presence of NPS through a combination of amnesty bin analysis, purchase analysis and information obtained from the Belgian Early Warning System Drugs. The relevant NPS identified from this research will be subjected to in vitro metabolism experiments in order to gather scientific information on their metabolic fate and to identify biomarkers to target in biomonitoring studies. Biomonitoring will be performed on different population levels through wastewater analysis (communities), pooled urine analysis (specific populations) and individual serum/urine samples in order to obtain data on the extent of NPS use in Belgium.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Neels Hugo
• Fellow: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

In order to comply with the REACH-regulations (Registration Evaluation and Authorization of Chemicals) and to improve animal welfare, a human based in vitro model to investigate the hepatotoxicity of new chemical entities (NCEs) will be developed. The designed model is based on an innovative approach combining in vitro methodology with LC-MS metabolomics, a recent – omics domain that examines alterations in the endogenous metabolic profile of cells and organisms. The basis of our model is the hepatic human HepaRG® cell line, which closely resembles primary hepatocytes in terms of metabolic capacity and toxicological response. In a first phase, the model will be developed by exposing HepaRG cell cultures to well known hepatotoxic compounds, such as acetaminophen, valproic acid, fluoxetine, bosentan and aflatoxine B1; the intracellular profile of the endogenous metabolites will be investigated in an untargeted approach using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-QTOF-MS). Differences between the metabolic profiles of exposed and unexposed cells will be examined using bioinformatics tools in order to identify possible biomarkers characteristic for the multiple hepatotoxic modes of action (MoA). A database containing the reference compounds, their MoAs and the corresponding specific biomarkers will be used in a targeted approach to investigate the hepatotoxic MoA of NCEs, including pharmaceutical and/or industrial compounds.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Laukens Kris
• Fellow: Cuykx Matthias

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The primary objective of the project is to respond to the EU draft regulation on the monitoring of BFRs in food. Indeed, there is a lack of information on the occurrence data of BFRs in food which has hampered an accurate completion of intake assessment by EFSA. Firstly, two analytical methods will be developed and validated. Due to the diverse nature of various BFRs which need to be included, a GC-MS and a LC-MSMS method needs to be developed. These two methods will be based on the methods available in the experienced laboratories of the three partners. The new methods will be in-house validated. Transfer of the methods from the partner responsible with the development of the method to the other partners will be the next step. To become acquainted with the analytical capabilities, a workshop will be organised for the FASFC and Belgian field laboratories towards the end of the project. Food samples of diverse food groups (fish & other seafood, meat and meat products (including edible offal), animal and vegetable fats and oils, milk and dairy products, eggs and egg products, food for infants and small children and feed for food producing animals,…) will be sampled and combined to obtain in total 200 pooled samples. The samples will be analysed by the 3 partners according the requirements in the draft regulation. The results will be reported to EFSA.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Jorens Philippe

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Environmental toxicology (named ecotoxicology further on) is by name a multidisciplinary field involving a wide span of scientifical domains These domains cover areas as biology (and several sub-disciplines thereof), ecology, biochemistry, toxicology, molecular genetics, industrial and process chemistry etc On top of that it touches the sociological field in terms of human and environmental hazard and risk, and even economy by setting environmental standards, thereby directly influencing industrial processes Water treatment technology and risk assessment are both important answers and tools offered to problems put forward by ecotoxicology Both offer and raise questions and problems to be answered It is my believe that ecotoxicology, in its broadest sense, holds the mother key in the solution but has yet to fully gain it.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Bols Peter
• Co-promoter: Covaci Adrian
• Co-promoter: De Wael Karolien
• Co-promoter: Geuens Luc
• Co-promoter: Janssens Koen
• Co-promoter: Knapen Dries
• Co-promoter: Lenaerts Silvia
• Co-promoter: Meire Patrick
• Co-promoter: Samson Roeland
• Fellow: Dardenne Freddy

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Bervoets Lieven
• Co-promoter: Covaci Adrian
• Co-promoter: Eens Marcel

Research team(s)

Project type(s)

• Research Project

Abstract

A novel approach is presented in order to characterize new lead compounds from natural sources. Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless, this aspect is usually overlooked when searching for new therapeutic agents using classical approaches. In this project, the Nauclea pobeguinii tree, Herniaria hirsuta herb, Salix spp. (willow bark) and Filipendula ulmaria (meadowsweet) were selected as case studies for the characterization of new leads for antimalarial, anti-nephrolithiasis, and anti-inflammatory drugs. LC-MS (Liquid Chromatography – Mass Spectrometry) and NMR (Nuclear Magnetic Resonance Spectroscopy) platforms will be established for the fast metabolic profiling of plant extracts, prepared using comprehensive extraction methods to cover the full range of constituents. Secondly, a gastro-intestinal dialysis model (GIDM) simulating human GI metabolization, will be applied in order to activate potential pro-drugs. In addition, the dialysate containing the GI metabolites will be treated with microsomal S9 fractions to mimic liver metabolization. The resulting metabolized samples (before and after S9 treatment) will be profiled using the same LC-MS and NMR platforms, and compared with the original profiles. At the same time all extracts and metabolized extracts will be pharmacologically evaluated in a range of in vitro assays related to antimalarial, anti-nephrolithiasis and anti-inflammatory properties. Pharmacological and chromatographic/ phytochemical data will be analyzed in a metabolomics approach using multivariate data analysis in order to identify pharmacologically active constituents or metabolites. Targeted isolation and final pharmacological evaluation in vitro and in vivo will yield new lead compounds against malaria, nephrolithiasis and inflammatory diseases.

Researcher(s)

• Promoter: Pieters Luc
• Co-promoter: Apers Sandra
• Co-promoter: Covaci Adrian
• Co-promoter: Hermans Nina

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless this aspect is usually overlooked when searching for new lead compounds for therapeutic agents. In this project Filipendula ulmaria (meadowsweet) and Herniaria hirsuta have been selected as case studies for the characterization of new leads for anti-inflammatory drugs, and drugs for nephrolithiasis. An LC-MS and 1H-NMR platform will be used for the fast metabolomic profiling of plant extracts, prepared using comprehensive extraction methods to cover the full range of constituents. Secondly, the platform will be extended with a dialysis model simulating human gastro-intestinal (GI) metabolization, which will be applied to activate potential pro-drugs. In addition, the dialysate containing the GI metabolites will be treated with microsomal S9 fractions to mimic liver metabolization. The resulting metabolized samples (before and after S9 treatment) will be profiled in the same LC-MS and 1H-NMR platform, and compared with the original profiles. At the same time all extracts and metabolized extracts will be pharmacologically evaluated in a range of in vitro assays related to anti-inflammatory and anti-nephrolithiasis properties. Pharmacological and chromatographic / phytochemical data will be analyzed in a metabolomics approach using multivariate data analysis in order to characterize the pharmacologically active constituents and their metabolites as new lead compounds.

Researcher(s)

• Promoter: Pieters Luc
• Co-promoter: Apers Sandra
• Co-promoter: Covaci Adrian
• Co-promoter: Laukens Kris
• Fellow: Bijttebier Sebastiaan

Research team(s)

Project type(s)

• Research Project

Abstract

An increasing number of "New Psychoactive Substances" (NPS), claiming to contain only "legal" compounds, has recently appeared on the drug market. One of the major concerns depends on the lack of suitable analytical methods to identify and also to quantify the NPS entering the market. Even using sophisticated analytical techniques, these new drugs may be missed, since reference standards are not always available. In addition, NPS are often extensively metabolized in the body making almost undetectable the parent compounds, which highlights the importance of identifying their metabolites. In the current proposal, we will analyze several suspicious drug preparations by taking advantage of a high-resolution/accurate-mass (HR/AM) spectrometer quadrupole/time-of-flight (QTOF) in order to achieve structural elucidation of their main active components. Metabolites of the identified NPS will be then obtained by in vitro human liver preparations and further characterized by high-performance-liquid chromatography (HPLC) coupled to QTOF mass spectrometry. Next, we will perform an approach based on "sewage epidemiology" to estimate the consumption of NPS via the analysis of NPS and their metabolites in wastewater. For this purpose, we will develop and validate an analytical method based on solid-phase extraction (SPE) and HPLC coupled to tandem mass spectrometry (MS/MS) for accurate analysis of identified NPS and their metabolites in both wastewater and pooled urine samples.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Negreira Ferrol Noelia

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed research will be divided in two main themes: 1) studying the exposure to emerging contaminants in Norwegian birds of prey and 2) assessing the potential effects of emerging contaminants, either alone via exposure experiments using a model bird species, a well as in combination with other pollutants occurring in free-living birds of prey.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed project is the extension of a PhD project within the larger framework of the INFLAME (Indoor Contamination with Flame Retardant Chemicals: Causes and Impacts) Marie Curie Initial Training Network (ITN) 2011-2014. The main research goal of the INFLAME is to understand how and to what extent flame retardant (FR) chemicals used in every-day consumer products enter humans and of the risk to health that such exposure presents. This project, entitled "Migration Pathways to the environment –"Horizon Scanning" for FRs present in consumer goods and construction materials", involved the investigation of the presence and characterization of flame retardants in a broad range of common consumer goods (electronics, furniture, carpets, curtains, plastic toys etc.) and building materials using analytical screening tools such as chromatography coupled to mass spectrometry (GC-MS and LC-TOFMS). The principal focus is on identifying and quantifying FRs hitherto either un- or rarely -detected. Any such "emerging" FRs detected in products are further investigated in specific matrices of the indoor environment, namely indoor air and dust. This work also provides analytical methods for "emerging" FRs, that will be further used by the INFLAME network. A special emphasis is given to direct analysis methods (such as direct probe) and to leaching tests.

Researcher(s)

• Promoter: Covaci Adrian
• Fellow: Ionas Alin

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand VUB. UA provides VUB research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Co-promoter: van Nuijs Alexander
• Fellow: Cappelle Delphine

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The main goals are: 1) to characterize most important exposure pathways for humans to OPFRs in the indoor environment and identify the compounds of concern; 2) to investigate the biotransformation of OPFRs using in vitro systems; 3) to develop innovative mass spectrometry-based metabolomic approaches for simultaneous detection of selected OPFRs and the endogenous metabolites (small molecules which are produced by the cell resulting from its normal functions) in exposed human hepatocytes; 4) to identify specific biomarkers (e.g. endogenous metabolites) impacted by exposure to OPFRs in hepatocytes. The project has been already initiated with the development of analytical methods necessary for the completion of the first goal, while procedures for the second goal are currently being developed. The completion of the proposed project will ensure a better understanding of the risk potential of OPFRs to human health provided by in vitro experiments.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Neels Hugo
• Fellow: Van den Eede Nele

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand Univ. Perpignan. UA provides Univ. Perpignan research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The main aim of this project is to study the impact of interactions between natural stressors and anthropogenic stress, caused by environmental contamination with OHCs, on the health of nestling birds of prey in (sub)Arctic regions. Birds of prey from (sub)Arctic regions have several characteristics that make them very useful to study OHC exposure in combination with natural stressors (see methodology).

Researcher(s)

• Promoter: Eens Marcel
• Co-promoter: Covaci Adrian
• Co-promoter: Jaspers Veerle

Research team(s)

• Behavioural Ecology & Ecophysiology

Project type(s)

• Research Project

Abstract

The main research goal of the project is to further understanding of how and to what extent consumer chemicals enter humans, and of how we can best monitor the presence of such chemicals in our indoor environment, diet and bodies. Our vision is that such enhanced understanding of the underpinning science will lead to more effective approaches to monitoring human exposure to chemicals within Europe, thereby improving assessment of risk associated both with recent and current-use consumer chemicals, as well as those under development, and leading ultimately to more sustainable approaches to the use of chemicals.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Federal Public Service. UA provides the Federal Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

SEWPROF aims to develop interdisciplinary and cross-sectoral research capability for the next generation of scientists working in the newly-emerging fileld of sewage epidemiology. It will provide an integrated approach towards public health monitoring at a community level based on innovative sewage epidemiology techniques.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Van Hal Guido
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

In this post-doctoral mandate, I will validate and refine an innovative approach for estimating illicit drug use in the general population based on sewage analysis for human excretion products of these substances ("sewage epidemiology"). In the first objective of this proposal, I will validate the approach by simultaneously executing a drug consumption questionnaire (the gold standard at this moment) and sewage epidemiology for a well-defined population and time period. The data resulting from both approaches will be compared and can serve as a validation of sewage epidemiology. The second objective focuses on refining sewage epidemiology back-calculations, by addressing the issue of estimating the population contributing to a specific sewage system in an objective, dynamic and real-time way. Different approaches for estimating the real amount of people contributing to a specific sewage system will be based on the analysis of specific markers in sewage that result from human activity. The last objective deals with applying sewage epidemiology for new and innovative purposes, such as the exploratory investigation of the use of new and emerging substances and through the execution of uniformed Europe-wide monitoring studies that allow reliable international comparisons on the epidemiology of illicit drug use. It is expected that the successful completion of these objectives will have positive implications for international drug policy and public health.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Jorens Philippe
• Co-promoter: Neels Hugo
• Fellow: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The main aim of the proposed research is to study exposure and effects of organic pollutants in predatory birds, using the white-tailed eagle (Haliaeetus albicilla; WTE) as a model species. The proposed research can be subdivided in several objectives. Firstly, I will study exposure through the development of physiologically based pharmacokinetic (PBPK) bioaccumulation models. Since a high amount of species-specific information is required to develop such a model, I have chosen the WTE as a model species. This species has been monitored for years through international collaborations and I have access to databases providing sufficient information for the first objective (see methodology). The second objective aims to study the effects from the physiological up to the population level. The last objective deals with the study of exposure to organic pollutants in the light of varying climate and feeding conditions over time.

Researcher(s)

• Promoter: Eens Marcel
• Co-promoter: Covaci Adrian
• Fellow: Jaspers Veerle

Research team(s)

• Behavioural Ecology & Ecophysiology

Project type(s)

• Research Project

Abstract

There are two principal strategies which will be followed, both of them being based on the experience accumulated in the field of analytical and environmental toxicology. A first strategy is to strengthen and expand the current research on food and environmental contaminants. A second major strategy is to develop new research directions which should preferably fit into the identified "spearheads" of the department of Pharmaceutical Sciences and of the University of Antwerp.

Researcher(s)

• Promoter: Covaci Adrian
• Fellow: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project aims to unravel the effects of DPP4 inhibition on collagen and collagen-derived dipeptide metabolism. We will develop and validate methods to quantify, in biological matrices, dipeptides resulting from DPP4 mediated cleavage. Next, the effects of DPP4 inhibition on the collagen metabolism and the dipeptide profile will be studied in vitro in fibroblast and osteoblast cultures. The in vivo relevance of our findings will be evaluated by studying the effects of long-term DPP4 inhibition in vivo in a rat model of type 2 diabetes. The focus will be on cardiac and renal collagen metabolism and dipeptide levels in plasma, urine and tissues.

Researcher(s)

• Promoter: De Meester Ingrid
• Co-promoter: Behets Geert
• Co-promoter: Covaci Adrian

Research team(s)

• Medical Biochemistry

Project type(s)

• Research Project

Abstract

This project comprises the identification of the active metabolites of selected natural products with a proven biological activity. The focus will be on Cranberry (Vaccinium macrocarpon) which is used against urinary tract infections, and the Congolese medicinal plant Nauclea pobeguinii, which showed promising activity against malaria in vitro as well as in vivo. For both plants, in vivo activity may be attributed to the formation of biologically active metabolites. The identification of these active metabolites involves the integrated application of in vitro and in vivo test systems with up-to-date technologies such as LC-MS (Liquid Chromatography – Mass Spectrometry) and LC-NMR (Liquid Chromatography – Nuclear Magnetic Resonance spectroscopy) combined with modern information technology such as MVA (multivariate data analysis) to process large amounts of data. These investigations on metabolites of selected natural products with a proven biological activity represent a challenging research field, whereas the successful completion of the submitted proposal might also lead to the characterisation of potential lead compounds for new drugs.

Researcher(s)

• Promoter: Apers Sandra
• Co-promoter: Covaci Adrian
• Co-promoter: Hermans Nina
• Co-promoter: Pieters Luc

Research team(s)

Project type(s)

• Research Project

Abstract

The overall vision of INTERFLAME is to enhance scientific understanding of how and to what extent organic flame retardant chemicals present in consumer goods and materials contaminate the environment, with particular reference to humans and wildlife. INTERFLAME's twin foci are exposure arising from indoor contamination and monitoring the efficacy of recent actions designed to reduce environmental levels.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Aims: Development of a physiologically based pharmacokinetic model for long-term uptake and accumulation of microcontaminants by seals. Model evaluation by comparison of predicted values with observed results of microcontaminants in blood and biopsy (living animals) and other tissues (dead animals). Determination of the condition of seals by use of general condition-indices and more specific indications for homeostasis and stress by analysis of bloodsamples with special attention for endocrine effects and immunity. Making connections between exposure, accumulation and effects. By comparison with results from analysis of animals from different areas and by use of multivariate statistical methods we will check whether it is possible to find the cause of the effects.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Fellow: Weijs Liesbeth

Research team(s)

Project type(s)

• Research Project

Abstract

The project aims firstly to characterize the presence, relevance and contribution of substitute phthalates and flame retardants in consumer goods (plastic materials, textiles, etc) and characterization of human exposure pathways (dietary and non-dietary: air, dust) to such chemicals. A general priority list for these new chemicals regarding their presence in indoor dust, air and food samples will be addressed in relation to their emission sources. Afterward, the identification of relevant biotransformation pathways of selected substitute chemicals present in the indoor environment through a combination of in vitro experiments and various mass spectrometry techniques will be the second important research direction of this project. Rat, pooled human liver microsomes and plasma will be used to characterize the metabolism of selected chemicals. Exposure experiments will be conducted with single and mixtures, at various doses relevant for the concentrations measured in indoor air, dust or food samples. Finally, the identification and quantification of parent compounds and their metabolites in human blood and urine samples will be performed in order to validate the results obtained from the in vitro experiments. The utility of non-invasive matrices (hair, nails, saliva) for providing accurate measures of internal exposure to selected new chemicals will also be evaluated.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Fellow: Dirtu Alin

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The main goals are: 1) to characterize most important exposure pathways for humans to OPFRs in the indoor environment and identify the compounds of concern; 2) to investigate the biotransformation of OPFRs using in vitro systems; 3) to develop innovative mass spectrometry-based metabolomic approaches for simultaneous detection of selected OPFRs and the endogenous metabolites (small molecules which are produced by the cell resulting from its normal functions) in exposed human hepatocytes; 4) to identify specific biomarkers (e.g. endogenous metabolites) impacted by exposure to OPFRs in hepatocytes. The project has been already initiated with the development of analytical methods necessary for the completion of the first goal, while procedures for the second goal are currently being developed. The completion of the proposed project will ensure a better understanding of the risk potential of OPFRs to human health provided by in vitro experiments.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Neels Hugo
• Fellow: Van den Eede Nele

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Federal Public Service. UA provides the Federal Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Biomonitoring of urine samples from mother and child pairs samples for chemical analysis of the Belgian part of the European LIFE + project DEMOCOPHES - lot 5: Chemical analysis of Bisphenol-A. Samples were collected in 2012 and results presented in 2012-2013. Coordinator: VITO

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Erasmus Mundus. UA provides Erasmus Mundus research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand a private institution. UA provides the private institution research results mentioned in the title of the project under the conditions as stipulated in this contract with the Muséum national d'histoire naturelle.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Erasmus Mundus. UA provides Erasmus Mundus research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand TNO. UA provides TNO research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The main research goal is to further understanding of how and to what extent flame retardant (FR) chemicals used in every-day consumer goods and construction materials enter humans and of the risk to health that such exposure presents.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Blust Ronny

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Fellow: Geens Tinne

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project aims at the development of models to estimate the use of illicit drugs in Belgium by means of the analysis of illicit drugs and their metabolites in wastewater ("sewage epidemiology"). Sewage epidemiology can deliver important and real-time information about local, regional, national and international illicit drug consumption which can be used in addition to classical socio-epidemiological studies to give policy makers a better picture about trends, patterns and hot-spots of illicit drug use.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Fellow: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Co-promoter: Jorens Philippe
• Co-promoter: Wijnants Marc

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The central aim of the proposed research project is the development of microarray derived molecular biomarkers for micro pollutants in the common carp (Cyprinus carpio) and validation of the selected set of biomarker genes under complex environmental relevant conditions. In order to be valuable in environmental risk evaluation the biomarker gene set has to meet several criteria.

Researcher(s)

• Promoter: Bervoets Lieven
• Co-promoter: Covaci Adrian
• Co-promoter: Jorens Philippe
• Co-promoter: Knapen Dries
• Co-promoter: Van der Ven Karlijn

Research team(s)

Project type(s)

• Research Project

Abstract

A fermentation based on feedstock sources from agro-food industry for the production of mannosylerythritol lipid biosurfactants (BIOMEL project) yields in a secretion of a complex blend of biomolecules with promising properties in food-, pharmaceutical, cosmetic and domestic housecare applications. The goal of this project is to define detailed protocols of standard procedures for isolation, purification, quantification and characterisation of current and novel MEL's from a complete fermentation broth.

Researcher(s)

• Promoter: Lemière Filip
• Co-principal investigator: Wijnants Marc
• Co-promoter: Covaci Adrian

Research team(s)

Project type(s)

• Research Project

Abstract

Brominated flame retardants (BFRs) have been used in commercial and household products, with a number of new BFRs (nBFRs) being recently introduced on the market. At this moment, very little is known regarding the environmental fate, food chain transfer, metabolism and toxicological profile of these nBFRs and this warrants additional and systematic research. The present proposal builds on the extensive experience and collaboration network related to BFRs accumulated in my first research mandate. A first objective is the validation of suitable analytical methods for the detection of nBFRs at trace levels in environmental and biological matrices. It further aims at a systematic investigation of the exposure routes, fate and biomagnification potential of nBFRs in representative aquatic and terrestrial food chains. This research will also aim at evaluating the degree and pathways of human exposure to nBFRs. Furthermore, the metabolic pathways of nBFRs in representative species, including humans, will also be investigated. Finally, the project will investigate the metabolic rates for the most important nBFRs. The completion of the proposed project will ensure a better understanding of the accumulation, fate and metabolism of nBFRs in biota.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Jorens Philippe
• Co-promoter: Neels Hugo
• Fellow: Covaci Adrian

Research team(s)

Project type(s)

• Research Project

Abstract

Aims: Development of a physiologically based pharmacokinetic model for long-term uptake and accumulation of microcontaminants by seals. Model evaluation by comparison of predicted values with observed results of microcontaminants in blood and biopsy (living animals) and other tissues (dead animals). Determination of the condition of seals by use of general condition-indices and more specific indications for homeostasis and stress by analysis of bloodsamples with special attention for endocrine effects and immunity. Making connections between exposure, accumulation and effects. By comparison with results from analysis of animals from different areas and by use of multivariate statistical methods we will check whether it is possible to find the cause of the effects.

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Fellow: Weijs Liesbeth

Research team(s)

Project type(s)

• Research Project

Abstract

The fundamental aim of this project is to develop and to validate a mathematical model to transform concentrations of the most prescribed and used pharmaceuticals and their metabolites of which the use is known (RIZIV) in waste water in an amount of used pharmaceuticals in Belgium (measured vs. predicted environmental concentrations).

Researcher(s)

• Promoter: Jorens Philippe
• Co-promoter: Bervoets Lieven
• Co-promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Co-promoter: Neels Hugo

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

The proposal aims at validating analytical methods based on liquid chromatography-mass spectrometry for the determination of various classes of priority pharmaceuticals in waste water. A first ever screening of these pharmaceuticals in waste water from Flanders will be done. Next, the identification of pharmaceuticals other than the target compounds and the evaluation of the stability of priority pharmaceuticals in waste water will also be investigated.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Neels Hugo
• Fellow: Tarcomnicu Isabela

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Fellow: Geens Tinne

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This projects consists of two parts. In the first part, methods of analysis for the determination of several drugs (cocaine, amphetamines, cannabis,...) and their metabolites in waste and surface water are being developped and validated. In the second part, the concentrations of drugs and metabolites found in watersamples will be used to estimate the abuse of drugs in Belgium.

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Fellow: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed project aims at investigating the pathways of human exposure to a class of emerging environmental contaminants, namely, the phenolic endocrine disruptors, such as bisphenol-A. After validating suitable analytical methods, the project aims at assessing the extent of exposure for the Flemish population and importance of each exposure route (e.g. via diet, air, dust, dermal contact). Special attention will be given to children's exposure.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

This projects consists of two parts. In the first part, methods of analysis for the determination of several drugs (cocaine, amphetamines, cannabis,...) and their metabolites in waste and surface water are being developped and validated. In the second part, the concentrations of drugs and metabolites found in watersamples will be used to estimate the abuse of drugs in Belgium

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian
• Fellow: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Bervoets Lieven
• Co-promoter: Blust Ronny
• Co-promoter: Covaci Adrian
• Co-promoter: Jorens Philippe

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: De Coen Wim
• Co-promoter: Bervoets Lieven
• Co-promoter: Covaci Adrian

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Neels Hugo
• Co-promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed project aims firstly at optimizing and validating analytical methods based on liquid chromatography-mass spectrometry (LC-MS) for the determination of metabolites of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in biological samples. Next, the project aims at identifying and predicting metabolisation pathways of PBDEs and PCBs in various top-predators.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Neels Hugo

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed project aims firstly at optimizing and validating analytical methods for the determination of emerging environmental contaminants, such as personal care products and phenolic chemicals, in human samples. An innovative part will be the assessment of human exposure to these contaminants, together with investigation of their major routes of exposure (food, air, particles, ¿).

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The proposed project aims at optimizing and validating analytical methods based on gas chromatography-mass spectrometry for the determination of the hydroxylated metabolites of polybrominated diphenyl ethers (HO-PBDEs) in biological samples. Next, it aims at identifying and predicting metabolisation pathways of PBDEs in various terrestrial top-predators and at investigating relationships between metabolites and parent compounds.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Neels Hugo
• Fellow: Zhao Hongxia

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Jorens Philippe
• Co-promoter: Neels Hugo
• Fellow: Covaci Adrian

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Blust Ronny
• Co-promoter: Jorens Philippe
• Co-promoter: Schepens Paul
• Fellow: Covaci Adrian

Research team(s)

Project type(s)

• Research Project

Abstract

The proposed project aims at optimizing and validating analytical methods for the determination of the flame retardant hexabromocyclododecane (HBCD) in environmental and biological samples. The technical HBCD used by the industry is not a pure substance but consists of different isomers, of which a-, b- and g-HBCD are the most abundant. Liquid chromatography coupled with mass spectrometry (LC/MS) will be used as analysis technique for the determination of individual HBCD isomers.

Researcher(s)

• Promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Neels Hugo
• Promoter: Schepens Paul
• Co-promoter: Covaci Adrian

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Eens Marcel
• Co-promoter: Covaci Adrian
• Co-promoter: Neels Hugo
• Co-promoter: Schepens Paul

Research team(s)

• Behavioural Ecology & Ecophysiology

Project type(s)

• Research Project