UZDRAVLJe – Health-related biomarkers’ comparison in people with different dietary habits

Collaborators: Goran Gajski, Isabel Moreno Indias, Martina Bituh, Selma Cvijetić Avdagić, Marijana Vučić Lovrenčić, Mirta Milić, Manuel Macias Gonzalez, Tatjana Orct, Luka Kazensky, Katarina Matković

Funding: Croatian Science Foundation

Call: IP-2025-02-2823

Project Duration: 31 Dec 2025 – 30 Dec 2028

Project Webpage: https://projekti.imi.hr/uzdravlje/

Project Summary
Diet is part of the human exposome that can be easily modified, yet it is one of the key factors in sustaining health and wellbeing. Despite thorough research describing the benefits of particular diet types, the results on their impact on human health are still inconclusive. UZDRAVLJe project aims to compare different dietary patterns using a multi-biomarker approach (nutritional profiling, body composition, baseline DNA damage, microbiome analysis, biochemical biomarkers, epigenetics) on a set of samples from human volunteers (N=200). An international multidisciplinary nutrigenomics team will tackle a problem of national and global relevance – diet-related impact on health biomarkers. The project’s outcomes include results that will interest the general public, the scientific community, legal bodies, and industry. Moreover, the project will improve capacity building and involvement of early career researchers in internationally relevant projects. Finally, the UZDRAVLJe project focuses on improving human health based on their dietary preferences aligning with S3 thematic priority personalised health care and supporting the environmental sustainability of the European Green Deal.


 

PROMETHEUS – Promoting Effective Transport through Healthy Bus Drivers

Project leaders: Goran Gajski (HR), Marina Otelea (RO) and Irina Guseva Canu (CH)

Project participants: Jelena Macan, Zrinka Franić, Marija Macan, Mirta Milić, Katarina Matković, Bruno Bekić, Luka Kazensky, Marija Kujundžić, Marko Gerić, Željka Babić, Blanka Tariba Lovaković, Tatjana Orct, Ankica Sekovanić, Irena Brčić Karačonji, Andreja Jurič, Sanja Stipičević, Darija Klinčić, Marija Dvoršćak, Karla Jagić Nemčić, Franka Šakić, Maja Nikolić, Adriana Gustovarac, Lucia Nanić, Emin Veledar, Daniela Prozorovscaia,  Thomas Charreau, Viviane Remy, Agripina Rascu, Claudia Handra, Sorina Hohor, Gabriela Louisse Neacsu, Cristina Mandanach, Ovidiu Popa-Velea

Project partners: Institute of Safety Research and Development (ZIRS), University Center for Primary Care and Public Health (UnisantĂ©), University of Medicine and Pharmacy “Carol Davila”

Financed by: Croatian Science Foundation and Swiss National Science Foundation

Call: Multilateral Academic Projects (MAPS-2024)

Duration: 1 July 2025 – 30 June 2029

Links:


 

Toxicity Assessment in 2D vs 3D cultures of Zebrafish liver cells (ZebTox3D)

Ministry of Science, Education and the Youth, Croatian-Slovenian Bilateral Cooperation, 2025-2026

Project Leader:

Leader in Slovenia:

  • MatjaĹľ Novak, National Institute of Biology (NIB), Ljubljana, Slovenia

Participants (IMROH):

Participants (NIB):

  • Bojana Ĺ˝egura
  • Alja Ĺ tern
  • Katja Kološa
  • Sonja Ĺ˝abkar
  • Iza Rozman

Summary
The zebrafish (Danio rerio) is one of the most important ecotoxicological models for studying the effects of pollutants. In accordance with the 3R principles (Reduce, Refine, Replace), in vitro models utilizing fish cell lines have been developed for xenobiotic toxicity assessment. Zebrafish liver epithelial cells (ZFL) possess the ability to metabolize various compounds and are widely used in toxicological research. However, data obtained from two-dimensional (2D) cultures have shown limitations in predicting in vivo responses, making 3D cultures a more relevant model due to their enhanced cellular differentiation, morphology, and gene expression. While 3D cultures are frequently used in mammalian toxicology studies, their application in ecotoxicology remains scarce. This project aims to establish ZFL 3D cultures as a model for toxicity assessment and to compare the responses of 2D and 3D systems to various pollutants, including bisphenols, nanoparticles, pharmaceutical residues, and polycyclic aromatic hydrocarbons. Cytotoxic and genotoxic effects will be evaluated through assays assessing cell viability, proliferation, migration, induction of cell death, and DNA damage. Comparing results between 2D and 3D models will enable the identification of the most suitable system for predicting in vivo responses. The project builds on a long-standing collaboration between Slovenian and Croatian research groups, leveraging their complementary expertise to advance in vitro methodologies in ecotoxicology. The expected outcomes of this research will contribute to new scientific insights, foster industry collaborations, and facilitate the education of young researchers. The findings will serve as a foundation for future international project applications, including those within the Horizon EU program.


 

EvaMobs – Evolvable and rapidly adaptable monobodies: a broad-spectrum antiviral platform

Consortium leader: Claudio M. Soares (ITQB Nova, Lisbon, Portugal)

Work package (WP3): Maja Katalinić

Participants (IMI): Antonio Zandona, Suzana Žunec

Programme: HORIZON

Call: HORIZON-HLTH-2023-DISEASE-03-04

Duration: 1. 1. 2024. – 31. 12. 2028.

Abstract
With progress in globalization, expansion of human populations into natural habitats, and aggravation of climate change comes an increased risk of viral outbreaks. As demonstrated by the COVID-19 pandemic, not being prepared for such events has devastating consequences on public health, society and the economy. EvaMobs will improve preparedness of the European Union (EU) for the next viral outbreak(s) of pandemic potential by developing a platform for the discovery, development, production and validation of evolvable and rapidly adaptable antivirals. These innovative medicines will be based on small human-derived proteins called monobodies (Mobs). As Mobs can be engineered to have high binding affinity for virtually any viral protein, this platform can be easily adapted to a broad range of viruses, including newly emerging viruses and viral variants. To demonstrate the capacity of this platform it will first be applied to four pathogenic viruses with epidemic and/or pandemic potential: Influenza A, SARS-CoV-2, respiratory syncytial virus, and Zika virus. Deep-learning and computational design tools will allow generation of tailor-made Mobs with cryo-EM elucidating the molecular details of their binding interaction. Simple bacterial expression of Mobs, the development of a semi-automated high-throughput screening platform for evaluation of the Mobs’ stability and target affinity and streamlined in vitro and in vivo preclinical validation, will allow rapid development and selection of stable and potently neutralizing candidates. The Mob with the best preclinical indicators will then be tested in a phase I clinical trial after implementing a stable formulation and GMP production. The optimized platform can then be adapted to other viruses. Therefore, EvaMobs provides an innovative, robust and flexible platform for antiviral biologics development as well as a diverse portfolio of validated drugs, strengthening the EU’s pandemic preparedness.

Link: https://evamobs.eu/


 

Effects of exposure to plasticizers and microplastics on men’s reproductive health

Croatian Science Foundation: Research project IP-2024-05-8815

Duration: 36 months, 16 Dec 2024 – 15 Dec 2027

Abstract
Along with the well-known phthalate esters (PAE), organophosphate esters (OPE) are a less researched class of plasticizers. Due to their properties, they are frequently added to consumer products, which is the main reason of the compounds’ widespread migration in the environment. The detection of PAEs and OPEs in the urine of the general public (both children and adults) has drawn the attention of scientists and regulatory agencies responsible for protection of human health and environment. Furthermore, the global rise in the use of disposable plastic items has led to an escalation in human contact with microplastics (MP). One of the main objectives of the PlastRepRisk project is to establish an analytical platform for analysing plasticizers (OPE, PAE) and MP particles in complex matrices such as human blood serum and urine. Main goal is to obtain preliminary data on the levels of exposure of the general population in Croatia to OPE and PAE compounds and MP particles. Although their health effects have not yet been fully elucidated, certain OPE and PAE compounds, as well as MPs, are suspected to act as endocrine disruptors and/or have detrimental effects on reproductive health. This study will also evaluate the risks to male reproductive health by comparing men diagnosed with infertility to healthy (fertile) subjects. Correlations between the concentrations of specific OPE, PAE, and MPs in blood/urine and infertility defined as a low count and/or poor quality of sperm and disruption in sex hormone levels will be assessed in order to investigate the hypothesis that exposure to plasticizers/MP may adversely affect reproductive function. The research will provide key insights into the possible impact of OPE, PAE, and MPs exposure on reproductive health disorders under actual exposure levels, in addition to obtaining first data on the levels of exposure of the Croatian population (men of reproductive age) to these compounds/particles.

Informing beekeepers about quality propolis (InfoBeePro)

Duration: 10 May 2024–31 Jan 2025

Total funding: 2,500.00 EUR

Donation from Hrvatska elektroprivreda d.d.: 1,400.00 EUR

Summary: Propolis has a high content of phenolic compounds that significantly contribute to its antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects. Therefore, the quality of propolis significantly depends on its phenolic composition. In addition to plant resins, bees can also collect various substances available in the environment, such as toxic elements (e.g. lead, cadmium, arsenic, mercury, etc.) that can be found in propolis. The aim of this project is to determine the level of toxic elements and bioactive components in propolis samples that will be collected in agreement with beekeepers from the Istrian and Primorje-Gorski Kotar counties. The main beneficiaries of the project will be beekeepers who collect propolis, and the results will be implemented through education on measures to reduce the negative impact of the environment on propolis and procedures for preparing propolis extracts with the highest content of bioactive components. Also, propolis consumers will be informed about the quality of Croatian propolis after determining the level of toxic and essential elements, phenolic compounds and antioxidant activity of the collected propolis samples. Additional propolis analyses are planned at locations where an increased proportion of toxic elements is determined, after implementing corrective measures aimed at reducing anthropogenic impacts (as part of field surveys). All research results will be based on modern scientific methods and will make a significant contribution to public health with the possibility of implementing the results in the Croatian economy for the general and national good, which is in line with the vision and mission of the Institute.

 

Analyses of interactions between organophosphorus compounds and esterases and other targets for therapy in poisoning (OPEsterOX)

Croatian Science Foundation: Research project IP-2022-10-6885

Team members: Goran Šinko, Tena Čadež, Dora Kolić, Višnja Stepanić, Vesna Gabelica Marković, Zoran Radić

Duration: 48 months, 2023-2027

Abstract

Exposure to organophosphates (OP) from both pesticides and nerve agents leads to the covalent inhibition of the pivotal enzyme acetylcholinesterase (AChE) that leads to accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Standard therapy of OP poisoning that generally involves administration of anticholinergic atropine and an oxime reactivator of phosphylated AChE has limitations especially in the case of phosphoroamidates due to the structural-related mechanism of reactivation. An alternative therapy is the related enzyme butyrylcholinesterase (BChE) which binds OP compounds and as such acts as stoichiometric bioscavenger of OP. Therefore, this project utilizes known (e.g. tabun, methamidophos and fenamiphos), and new compounds (A-agents) to gain a better understanding of the mechanistic basis of cholinesterase family interactions and their limitations to find new effective leads for treatment. The biochemical mechanism of enzyme interactions will be comprehensively studied on a molecular level with in silico, in vitro, and ex vivo methods to define binding affinities, kinetic constants of inhibition and efficiency of reactivation of both enzymes. The possible mechanisms of toxicity of selected OPs will be studied at cell-culture level, and on mice exposed to OP. The neuroinflammatory effect of OP as w ell as the neuroprotective effectiveness of oxime therapy will be examined on the mouse brain by monitoring specific markers of astrogliosis, microgliosis and neuron viability. These comprehensive analyses will undoubtedly contribute to the knowledge of phosphoroamidate interactions and improved therapeutics in OP poisoning.

Publications
  • MaÄŤek Hrvat, Nikolina; Puljko, Borna; Sit, Rakesh K.; Ilić, Katarina; Kolić, Dora; Mlinac-Jerkovic, Kristina; Kalanj-Bognar, Svjetlana; Radić, Zoran; Sharpless, Barry K.; Taylor, Palmer et al. The ionizing zwitterionic oxime antidote attenuates gliosis in mice exposed to sarin. Chem-Biol Interact, 421 (2025), 111767, 8. doi: 10.1016/j.cbi.2025.111767
  • ÄŚadeĹľ, Tena; MaÄŤek Hrvat, Nikolina; Ĺ inko, Goran; Kalisiak, JarosĹ‚aw;  Radić, Zoran; Fokin, Valery V.;  Sharpless, Karl Barry;  Taylor, Palmer;  Kovarik, Zrinka. Click-chemistry-derived oxime library reveals efficient reactivators of nerve agent-inhibited butyrylcholinesterase suitable for pseudo-catalytic bioscavenging. Arch Toxicol (2025) https://doi.org/10.1007/s00204-025-03985-6
  • Kovarik, Zrinka; Kolić, Dora; ÄŚadeĹľ, Tena; Ĺ inko, Goran; Tuksar, Petra; Zorbaz, Tamara; Curty, Christophe; MaÄŤek Hrvat, Nikolina. Outlining the A-series of organophosphorus compounds: Cholinesterase inhibition, reactivation, cytotoxicity, and acute toxicity in mice. Chem-Biol Interact, 421 (2025), 111762, 11. doi: 10.1016/j.cbi.2025.111762
  • Kolić, Dora; Kovarik, Zrinka. N-methyl-d-aspartate receptors: Structure, function, and role in organophosphorus compound poisoning. BioFactors, 50(5), 2024, 868–884.
  • Mlakić, Milena; ÄŚadeĹľ, Tena; Ĺ inko, Goran; Ĺ korić, Irena; Kovarik, Zrinka. New Heterostilbene and Triazole Oximes as Potential CNS-Active and Cholinesterase-Targeted Therapeutics. Biomolecules, 14(6), 2024, 679(37)
Dissemination
  • 19th Medical Chemical Defense Conference, Munchen, NjemaÄŤka (2. – 3. 4. 2025.).
    Posterska prezentacija: The efficacy of centrally active RS oximes in reactivating phosphorylated acetylcholinesterase (N. MaÄŤek Hrvat)
    Posterska prezentacija: Assessment of nerve agent-induced toxicity in a cellular model (T. ÄŚadeĹľ)
  • Mini-symposium “Multidisciplinarity in drug development”, Zagreb, Hrvatska (12. 2. 2025.)
    Pozvano predavanje: Targeting organophosphorus poisoning by pseudocatalytic detoxification system (T. ÄŚadeĹľ)
  • 49th FEBS Congress: Bridging Continents to Advance Life Sciences, Istanbul, Turska, (5. – 9. 7. 2025.)
    Posterska prezentacija: Identifying cholinesterase inhibitors among commercially available pesticides by bioinformatic analysis and in vitro inhibition (Maček Hrvat, Nikolina; Stepanić, Višnja; Šinko, Goran; Čadež, Tena)
    Posterska prezentacija: Evaluation of compounds as multitarget therapeutics in neurological disorders (Čadež, Tena; Mlakić, Milena; Škorić, Irena; Maček Hrvat, Nikolina; Kovarik, Zrinka)
  • 59th Congress of the European Societies of Toxicology, Atena, GrÄŤka (14. – 17. 9. 2025.)
    Posterska prezentacija Disruption of the plasma membrane organization and neuroinflammation can be triggered by toxic organophosphorus compounds (Maček Hrvat, Nikolina; Puljko, Borna; Ilić, Katarina; Mlinac-Jerković, Kristina; Kalanj-Bognar, Svjetlana)
    Posterska prezentacija Organophosphorus pesticides and neurotoxicity: Evaluation of human and animal cell model (ÄŚadeĹľ, Tena; MaÄŤek Hrvat, Nikolina)
  • 10. hrvatski kongres neuroznanosti, Zagreb, Hrvatska (11. – 13. 9. 2025.)
    Kratka oralna prezentacija postera: Imidazolium oximes for the management of organophosphate compound neurotoxicity (D. Kolić, I. Primožič, Z. Kovarik, N. Maček Hrvat)
  • 48th FEBS Congress: Mining biochemistry for human health and well-being, Milano, Italija (29.06.2024 – 03.07.2024).
    Posterska prezentacija: New and old challenges in reversing organophosphorus toxicity (N. Maček Hrvat, D. Kolić, T. Čadež, Z. Kovarik).
  • EUROTOX2024: Toxicology – A Quest for safe Chemicals and Medicines, Copenhagen, Danska (08.09.2024 – 11.09.2024).
    Posterska prezentacija: Assessment of organophosphate-induced toxicity and evaluation of antidotal efficacy on cellular level (T. Čadež, Z. Kovarik).
  • ChEPON, 15th International Meeting on Cholinesterases, 9 th International Conference on Paraoxonases, Brdo pri Kranju, Slovenija (15.09.2024 – 18.09.2024).
    Posterske prezentacije: Outlining the A-series of organophosphorus compounds – cholinesterase inhibition, reactivation, cytotoxicity (Nikolina Maček Hrvat, Dora Kolić, Tena ČadeŽ, Goran Šinko, Zrinka Kovarik);
    Evaluation of resveratrol compounds as therapeutics in organophosphorus poisoning (Tena Čadez, Milena Mlakić, Nikolina Maček Hrvat, Irena Škorić, Zrinka Kovarik).
  • FEBS3+ Meeting: Exploring Molecular Frontiers, Pula, Hrvatska (25.09.2024 – 28.09.2024).
    Posterska prezentacija: Bioscavenging capacity of butyrylcholinesterase reduces Inhibition impact of organophosphate compounds in human blood (Dora Kolić, Goran Šinko, Ines Primožič, Zrinka Kovarik).
  • HKD simpozij: 8th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry, Zagreb, Hrvatska, (19. 11. 2024.).
    Predavanje: CNS-active ligands against neurotoxocity in organophosphate compound poisoning (Dora Kolić, Nikolina Maček Hrvat, Zoran Radić, Zrinka Kovarik).
Training
  •  Biocentar, Zagreb – workshops:
    ”Proizvodnja, pročišćavanje i karakterizacija proteina” (25.-27.11.2025.) – D. Kolić and P. Nakić
    Chemical codes – biostatistika u R-u, napredna razina (6.-7.11.2025.) – T. Čadež
    Chemical codes – biostatistika u R-u, osnovna razina (23.-29.10.2025.) – T. Čadež
  • Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK (11.7.-12.9.2025.) – T. ÄŚadeĹľ
  • Skaggs School of Pharmacy and Pharmaceutical Sciences of the UC San Diego in La Jolla,CA, USA (1.2.-16.3.2024.) – D. Kolić
  • The 2nd Course on Molecular Toxicology, Izmir, Turska (22.–24.5.2024.) – D. Kolić
Mentoring
  • Graduate thesis ËťBiosigurnost i uÄŤinkovitost oksima za reaktivaciju kolinesteraza nakon otrovanja organofosfatimaËť – Ema Krstulović (Faculty of Science, University of Zagreb)

Environment pollution and human health: physico-chemical analysis, toxicity, and machine learning models

Acronym: EnvironPollutHealth

Duration: 1 Jan 2024–31 Dec 2027

Funded by the European Union – Next Generation EU
– Program Contract of 8 Dec 2023, Class: 643-02/23-01/00016, Reg. no. 533-03-23-0006
Funding: 460,652.00 EUR

Holder: Institute for Medical Research and Occupational Health, Division of Environmental Hygiene

Partners:

  • University of Belgrade, Faculty of Chemistry, Department of Applied Chemistry (Belgrade, Serbia)
  • University of Belgrade, Institute of Physics, Environmental Physics Laboratory (Belgrade, Serbia)
  • University of Zadar, Department of Health Studies (Zadar, Croatia)
  • University of Zadar, Department of Ecology, Agronomy and Aquaculture (Zadar, Croatia)
  • University of Zagreb, Faculty of Agriculture, Department of General Agronomy (Zagreb, Croatia)
  • University of Zagreb, Faculty of Agriculture, Department of Soil Amelioration (Zagreb, Croatia)
  • University of Zagreb, Faculty of Mining Geology and Petroleum Engineering, Department of Mineralogy, Petrology and Mineral Resources (Zagreb, Croatia)
  • University of Zagreb, Faculty of Forestry and Wood Technology, Institute of Processes Engineering (Zagreb, Croatia)
  • Institute for Anthropological Research, Laboratory for Chemical Analytics (Zagreb, Croatia)
  • AQUATIKA – Karlovac Freshwater Aquarium (Karlovac, Croatia)

More info about the project

Interactions between Human and Environmental Health: Determinants of Health Preservation – HumEnHealth

More info about the project available at: https://projekti.imi.hr/humenhealth/en/

This project, in line with the One Health approach of the World Health Organization, aims to integrate research for a better understanding of the health status of specific environmental and animal systems. The goal is to understand their impact on human health, explore ways to detect health disorders in humans and the environment early, and identify methods for prevention. The research will encompass potential interactions among genetic, nutritional, and psychosocial factors contributing to health disorders caused by pollutants in the living and working environment. Additionally, the project will investigate possibilities to enhance the methodology of epidemiological studies and improve statistical data processing methods.

The project will focus on:
1. Chemical pollutants (metals, pesticides, biocides, skin allergens, and irritants).
2. Physical pollutants (noise).
3. Psychosocial factors (personal and organizational stressors, broader social context stressors).

The environmental burden will be analyzed in aquatic organisms, water, sediment, plants, and animals in terrestrial ecosystems and/or food. Biochemical mechanisms of nutrient and pollutant action will be explored using in silico methods. Human organism load will be studied through biomonitoring methods, investigating health disorders such as skin inflammation, obesity, osteoporosis, neurobehavioral disorders, developmental disorders, plant and animal poisoning, vitamin and mineral deficiencies, and hearing damage caused by noise, using clinical and psychological methods.

The main project goal is to investigate the health status of selected environmental and animal systems, their impact on human health, early detection methods for human and environmental health disorders, and ways to improve prevention.

Specific project objectives include:
1. Examining the distribution and accumulation of metal(oid)s in target organs of tissues in animal indicator species.
2. Assessing nutrient intake and exposure to major food and water pollutants, evaluating potential health risks and characterizing plant and fungal poisonings in the population.
3. Assessing metal(loid) exposure (Cd, Pb, Hg, As) via dietary and lifestyle habits in the general and vulnerable population using human biomonitoring; evaluating the association between toxic and essential elements and genetic polymorphisms, including epigenetic and metabolomic effects; and developing the new analytical methods for element determination in biological samples.
4. Investigation of the effects of genetic factors and environmental chemicals on the development of occupational skin diseases; estimating the skin barrier function parameters as early biomarkers of skin diseases; assessing the occupational health and safety status in high-risk populations; and conducting an educational intervention to improve the prevention of occupational skin diseases.
5. Studying recreational headphone use in young adults, measuring noise exposure and its potential association with hearing damage.
6. Identifying enzymatic reactions of tyrosinase at the molecular level for understanding the development and treatment of Parkinson’s disease.
7. Assessing sleep quality and daily functioning in different age groups in relation to chemical and psychosocial factors.
8. Examining and proposing statistical methods for analyzing data from various sources in the assessment of chemical exposure and harmful effects.

The research will be conducted through seven work packages, each focusing on specific aspects of the project:

Work Package 1. Environmental Health (leader Zorana Kljaković-Gašpić) Considering a wide range of factors and their complex interactions, this work package will investigate the levels of metal(oid)s (both essential and potentially toxic) in abiotic components of the environment (soil, water, and sediment) and bioindicator organisms at different trophic levels of aquatic and terrestrial food webs, including some rarely covered by monitoring programs (rare and/or protected species). The pathways of metal(oid) transfer and accumulation between different ecosystem components will be explored, depending on biological and ecological influencing factors. The connection between the content of elements in target tissues of accumulation, indicators of oxidative stress (effect biomarkers), protein indicators of exposure (metallothionein, MT), and hormones in blood and hair (cortisol, testosterone, progesterone, total and free thyroxine, total and free triiodothyronine, and thyroid-stimulating hormone) will be investigated.

Work Package 2. Food and Health (leader Antonija Sulimanec) By additional sampling of food and analyses, not only of pesticides but also various metal(oid)s, encompassing the diet of female adolescents and the adult population of both genders, is planned to contribute to a better definition of the exposure of the Croatian population to major contaminants in food and drinking water. Poorly understood mechanisms of action and the degree of toxicity of endocrine disruptors will be investigated, as well as inter-individual differences in sensitivity to these toxins in the human population during puberty. The harmful effects of exposure to low doses of toxic chemical mixtures on human health will also be explored. We will continue with developing of the theoretical models for the evaluation of oxidation potentials and antioxidant activities of flavonoids.

Work Package 3. Human biomonitoring and (epi)genetic (leader Ankica Sekovanić) This work package aims to investigate the impact of daily environmental exposure to chemicals, dietary and lifestyle habits, and genetic factors on biomarkers of exposure, epigenetic and metabolomic changes, and the occurrence of clinically manifested health disorders in humans, including occupational diseases. The study will examine the following: 1) the influence of MT2A and MTHFR gene polymorphisms on biomarkers of metal exposure and biochemical parameters (glucose, lipid, and nutritional status) in the general population (men and women) and/or in the vulnerable population (mother-newborn pairs); 2) the effects of TNF-α polymorphisms and chemical exposure on the occurrence of work-related skin disorders among hairdressing students; and 3) the prevalence of gene polymorphisms in proteins that are implicated in metabolism of xenobiotics (e.g., P-glycoprotein, cytochrome P450, glutathione-S-transferase) and their association with biomarkers of dietary pesticide exposure among adolescents.

Work Package 4. Mental Health (leader Adrijana Bjelajac) This work package aims to integrate insights into the relationships between sleep and daily functioning of different age groups exposed to different combinations of harmful environmental influences. In collaboration with work packages 2, 5, and 7, the knowledge gained from previous studies on sleep quality and daily functioning of different age groups (adolescents, adults, the elderly) in the context of exposure to harmful chemical and psychosocial factors will be analyzed. Enzymatic reaction mechanisms of tyrosinase at the molecular level will be identified by combining molecular modeling methods with experimental data from the literature.

Work Package 5. Occupational Safety and Health (leader Željka Babić) In this work package, research will be conducted to improve the prevention of occupational skin diseases in high-risk populations of hairdressing students and students for the profession of medical nurse/technician who are regularly exposed to a range of chemicals with harmful effects on the skin during practical training. Research will be conducted on three levels: 1) knowledge and application of occupational safety measures and other measures for the prevention of skin disorders during the vocational education of Croatian hairdressing students (use of protective gloves, method and frequency of hand skin washing and care); 2) through the design of a prospective cohort study, the predictive value of parameters of skin barrier function for the early detection of the development of inflammatory skin disorders related to work will be examined, contributing to primary and secondary prevention of occupational skin diseases; skin barrier function will be examined by non-invasive methods of measuring transepidermal water loss (TEWL), skin pH, hydration, and temperature; 3) based on the results of the above research, a preliminary educational intervention study will be conducted, including lectures, written popular materials, and gift packages for students and/or workers in selected schools and/or workplaces in the Republic of Croatia.

Work Package 6. Noise (leader Marija Kujundžić) This work package will investigate the habits of recreational headphone use in individuals aged 18 to 40. The sound intensity in headphones that respondents usually apply in quiet and noisy environments will be determined, hearing will be assessed by audiometry, and the association between headphone use and possible hearing damage will be evaluated. The innovation of the research is reflected in the assessment of noise exposure by direct measurement of noise exposure, i.e., measuring the sound volume applied by respondents in headphones, which will allow a better assessment of the relationship between exposure and health damage.

Work Package 7. Scientific Research Methodology (leader Jelena Kovačić) The goal of this research is to examine and propose methods for analyzing data from multiple sources (such as data generated within the framework of other work packages, data from the literature, including open-access data and summary data from publications, in silico data on the structure and physicochemical properties of pollutants, and freely available data used for regulatory purposes) in assessing exposure and adverse effects of chemicals. Statistical models and machine learning models allowing the inclusion of different types of data in one model will be explored for data analysis, such as models used in meta-analyses, Bayesian models enabling the inclusion of expert knowledge and results from analyses from other sources in the form of model parameters, and probabilistic graphical models. In collaboration with work packages 2, 4, and 5, the features of epidemiological self-assessment methods (questionnaires) will be evaluated as alternatives to objective measures (e.g., clinical diagnosis of diseases or measurements of biomarkers as indicators of exposure) due to the simplicity of their application, especially in situations where implementing more objective measures would be financially, temporally, or logistically challenging.


 

Exposure to pyrethroid and organophosphate insecticides in children – risk assessment for adverse effects on neuropsychological development and hormonal status (PyrOPECh)

Croatian Science Foundation research project
IP-2019-04-7193
Participants: Jelena Kovačić, Adrijana Bjelajac, Jasminka Bobić (do 2022), Selma Cvijetić Avdagić, Jelena Macan, Rajka Turk, Martina Piasek (do 2020), Željka Babić, Jim Garvey, Marija Posavec, Vera Musil, Bernarda Krnić, Marijana Matek Sarić, Irena Keser, Saša Kralik Oguić, Iva Bebek, Gordana Jurak, Tatjana Petričević-Vidović, Anne Nugent, Matijana Jergović, Romana Gjergja Juraški, Snježana Sekušak-Galešev, Breige McNulty, Katja Dumić Kubat, Brendan Murray, Andreja Jurič, Marija Macan, Antonija Sulimanec Grgec, Patricia Tomac, Eva Anđela Delale
Head: Veda Marija Varnai
Summary
Epidemiological studies and animal experiments indicate the potential adverse effects of exposure to pyrethroid (PYR) and organophosphate (OP) insecticides on brain and sexual development in children, even at very low exposure levels. However, limited number of studies explored these potential risks during puberty, with inconsistent results and significant methodological limitations, such as insufficiently assessed exposure and cross-sectional study design. The main objective of the proposed research is to assess the risk of PYR and OP insecticide exposure to neuropsychological development and hormonal status in prepubertal and pubertal boys in a 2-year cohort study, while controlling for potential confounders, and using only non-invasive methods. Children’s exposure to PYR and OP insecticides will be assessed by biomonitoring (analysing urinary pesticide metabolites) in the 5th and 7th grades of elementary school, and by dietary exposure assessment – 24-hour dietary recall on five occasions during 2-year follow-up. In the 5th and 7th grades, neuropsychological development will be evaluated by testing attention, memory and simple psychomotor response speed, and by assessing the characteristics of child’s sleep and behaviour. Pubertal development will be evaluated by clinical examination (according to Tanner and Prader), and urinary gonadotropins and salivary sex hormones (testosterone and dehydroepiandrosterone sulfate) measurements. The research is expected to 1) increase the knowledge on possible risks of PYR and OP insecticides’ exposure for neurodevelopment and hormonal status in pubertal boys; 2) help to recognise deficiencies and assess available methodology for evaluation of developmental neurotoxicity and endocrine disruption within the framework of regulatory toxicology; 3) improve insufficient methodology for exposure assessment of non-bioaccumulative pesticides; 4) contribute to the better characterisation of pesticide exposure in the Croatian population.