Percorrer por autor "Mustieles, Vicente"
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- Biomarkers of effect as determined in human biomonitoring studies on hexavalent chromium and cadmium in the period 2008-2020Publication . Ventura, Célia; Gomes, BC; Oberemm, Axel; Louro, Henriqueta; Huuskonen, Pasi; Mustieles, Vicente; Fernández, Mariana F.; Ndaw, Sophie; Mengelers, Marcel; Luijten, Mirjam; Gundacker, Claudia; Silva, Maria JoãoA number of human biomonitoring (HBM) studies have presented data on exposure to hexavalent chromium [Cr(VI)] and cadmium (Cd), but comparatively few include results on effect biomarkers. The latter are needed to identify associations between exposure and adverse outcomes (AOs) in order to assess public health implications. To support improved derivation of EU regulation and policy making, it is of great importance to identify the most reliable effect biomarkers for these heavy metals that can be used in HBM studies. In the framework of the Human Biomonitoring for Europe (HBM4EU) initiative, our study aim was to identify effect biomarkers linking Cr(VI) and Cd exposure to selected AOs including cancer, immunotoxicity, oxidative stress, and omics/epigenetics. A comprehensive PubMed search identified recent HBM studies, in which effect biomarkers were examined. Validity and applicability of the markers in HBM studies are discussed. The most frequently analysed effect biomarkers regarding Cr(VI) exposure and its association with cancer were those indicating oxidative stress (e.g., 8-hydroxy-2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH)) and DNA or chromosomal damage (comet and micronucleus assays). With respect to Cd and to some extent Cr, β-2-microglobulin (B2-MG) and N-acetyl-β-D-glucosaminidase (NAG) are well-established, sensitive, and the most common effect biomarkers to relate Cd or Cr exposure to renal tubular dysfunction. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 could serve as sensitive biomarkers of acute kidney injury in response to both metals, but need further investigation in HBM studies. Omics-based biomarkers, i.e., changes in the (epi-)genome, transcriptome, proteome, and metabolome associated with Cr and/or Cd exposure, are promising effect biomarkers, but more HBM data are needed to confirm their significance. The combination of established effect markers and omics biomarkers may represent the strongest approach, especially if based on knowledge of mechanistic principles. To this aim, also mechanistic data were collected to provide guidance on the use of more sensitive and specific effect biomarkers. This also led to the identification of knowledge gaps relevant to the direction of future research.
- Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030Publication . Zare Jeddi, Maryam; Hopf, Nancy B.; Louro, Henriqueta; Viegas, Susana; Galea, Karen S.; Pasanen-Kase, Robert; Santonen, Tiina; Mustieles, Vicente; Fernandez, Mariana F.; Verhagen, Hans; Bopp, Stephanie K.; Antignac, Jean Philippe; David, Arthur; Mol, Hans; Barouki, Robert; Audouze, Karine; Duca, Radu-Corneliu; Fantke, Peter; Scheepers, Paul; Ghosh, Manosij; Van Nieuwenhuyse, An; Lobo Vicente, Joana; Trier, Xenia; Rambaud, Loïc; Fillol, Clémence; Denys, Sebastien; Conrad, André; Kolossa-Gehring, Marike; Paini, Alicia; Arnot, Jon; Schulze, Florian; Jones, Kate; Sepai, Ovnair; Ali, Imran; Brennan, Lorraine; Benfenati, Emilio; Cubadda, Francesco; Mantovani, Alberto; Bartonova, Alena; Connolly, Alison; Slobodnik, Jaroslav; Bruinen de Bruin, Yuri; van Klaveren, Jacob; Palmen, Nicole; Dirven, Hubert; Husøy, Trine; Thomsen, Cathrine; Virgolino, Ana; Röösli, Martin; Gant, Tim; von Goetz, Natalie; Bessems, JosHuman biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission’s Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond. We outline six strategic objectives and a roadmap to further strengthen HBM approaches and increase their implementation in the regulatory risk assessment of chemicals to enhance our understanding of exposure and health impacts, enabling timely and targeted policy interventions and risk management. These strategic objectives are: 1) further development of sampling strategies and sample preparation; 2) further development of chemical-analytical HBM methods; 3) improving harmonisation throughout the HBM research life cycle; 4) further development of quality control / quality assurance throughout the HBM research life cycle; 5) obtain sustained funding and reinforcement by legislation; and 6) extend target-specific communication with scientists, policymakers, citizens and other stakeholders. HBM approaches are essential in risk assessment to address scientific, regulatory and societal challenges. HBM requires full and strong support from the scientific and regulatory domain to reach its full potential in public and occupational health assessment and in regulatory decision-making.
- Guidance on minimum information requirements (MIR) from designing to reporting human biomonitoring (HBM)Publication . Jeddi, Maryam Zare; Galea, Karen S.; Ashley-Martin, Jillian; Nassif, Julianne; Pollock, Tyler; Poddalgoda, Devika; Kasiotis, Konstantinos M.; Esteban-López, Marta; Chung, Ming Kei; Kil, Jihyon; Jones, Kate; Covaci, Adrian; Ait Bamai, Yu; Fernandez, Mariana F.; Pasanen Kase, Robert; Louro, Henriqueta; Silva, Maria J.; Santonen, Tiina; Katsonouri, Andromachi; Castaño, Argelia; Quirós-Alcalá, Lesliam; Argelia Castaño; Lesliam Quirós-Alcalá; Lin, Elizabeth Ziying; Pollitt, Krystal; Ana Virgolino; Virgolino, Ana; Scheepers, Paul T.J; Mustieles, Vicente; Cañas-Portilla, Ana Isabel; Viegas, Susana; von Goetz, Natalie; Sepai, Ovnair; Bird, Emily; Gӧen, Thomas; Fustinoni, Silvia; Ghosh, Manosij; Dirven, Hubert; Kwon, Jung-Hwan; Carignan, Courtney; Mizuno, Yuki; Ito, Yuki; Xia, Yankai; Shoji F. Nakayama; Nakayama, Shoji F.; Makris, Konstantinos C.; Parsons, Patrick J.; Gonzales, Melissa; Bader, Michael; Dusinska, Maria; Menouni, Aziza; Duca, Radu Corneliu; Chbihi, Kaoutar; El Jaafari, Samir; Godderis, Lode; van Nieuwenhuyse, An; Qureshi, Asif; Ali, Imran; Costa Trindade, Carla; Teixeira, Joao Paulo; Bartonova, Alena; Tranfo, Giovanna; Audouze, Karine; Verpaele, Steven; LaKind, Judy; Mol, Hans; Bessems, Jos; Magagna, Barbara; Nasution Waras, Maisarah; Connolly, Alison; Nascarella, Marc; Yang, Wonho; Huang, Po-Chin; Heussen, Henri; Goksel, Ozlem; Yunesian, Masud; Yeung, Leo W.Y.; Souza, Gustavo; Vekic, Ana Maria; Haynes, Erin N.; Hopf, Nancy B.Human biomonitoring (HBM) provides an integrated chemical exposures assessment considering all routes and sources of exposure. The accurate interpretation and comparability of biomarkers of exposure and effect depend on harmonized, quality-assured sampling, processing, and analysis. Currently, the lack of broadly accepted guidance on minimum information required for collecting and reporting HBM data, hinders comparability between studies. Furthermore, it prevents HBM from reaching its full potential as a reliable approach for assessing and managing the risks of human exposure to chemicals. The European Chapter of the International Society of Exposure Science HBM Working Group (ISES Europe HBM working group) has established a global human biomonitoring community network (HBM Global Network) to develop a guidance to define the minimum information to be collected and reported in HBM, called the “Minimum Information Requirements for Human Biomonitoring (MIR-HBM)”. This work builds on previous efforts to harmonize HBM worldwide. The MIR-HBM guidance covers all phases of HBM from the design phase to the effective communication of results. By carefully defining MIR for all phases, researchers and health professionals can make their HBM studies and programs are robust, reproducible, and meaningful. Acceptance and implementation of MIR-HBM Guidelines in both the general population and occupational fields would improve the interpretability and regulatory utility of HBM data. While implementation challenges remain—such as varying local capacities, and ethical and legal differences at the national levels, this initiative represents an important step toward harmonizing HBM practice and supports an ongoing dialogue among policymakers, legal experts, and scientists to effectively address these challenges. Leveraging the data and insights from HBM, policymakers can develop more effective strategies to protect public health and ensure safer working environments.
- A human biomonitoring (HBM) Global Registry Framework: Further advancement of HBM research following the FAIR principlesPublication . Zare Jeddi, Maryam; Virgolino, Ana; Fantke, Peter; Hopf, Nancy B.; Galea, Karen S.; Remy, Sylvie; Viegas, Susana; Mustieles, Vicente; Fernandez, Mariana F.; von Goetz, Natalie; Vicente, Joana Lobo; Slobodnik, Jaroslav; Rambaud, Loïc; Denys, Sébastien; St-Amand, Annie; Nakayama, Shoji F.; Santonen, Tiina; Barouki, Robert; Pasanen-Kase, Robert; Mol, Hans G.J.; Vermeire, Theo; Jones, Kate; Silva, Maria João; Louro, Henriqueta; van der Voet, Hilko; Duca, Radu-Corneliu; Verhagen, Hans; Canova, Cristina; van Klaveren, Jacob; Kolossa-Gehring, Marike; Bessems, JosData generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF.
- Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledgePublication . Rodríguez-Carrillo, Andrea; Mustieles, Vicente; Salamanca-Fernández, Elena; Olivas-Martínez, Alicia; Suárez, Beatriz; Bajard, Lola; Baken, Kirsten; Blaha, Ludek; Bonefeld-Jørgensen, Eva Cecilie; Couderq, Stephan; D'Cruz, Shereen Cynthia; Fini, Jean-Baptiste; Govarts, Eva; Gundacker, Claudia; Hernández, Antonio F.; Lacasaña, Marina; Laguzzi, Federica; Linderman, Birgitte; Long, Manhai; Louro, Henriqueta; Neophytou, Christiana; Oberemn, Axel; Remy, Sylvie; Rosenmai, Anna Kjerstine; Saber, Anne Thoustrup; Schoeters, Greet; Silva, Maria João; Smagulova, Fatima; Uhl, Maria; Vinggaard, Anne Marie; Vogel, Ulla; Wielsøe, Maria; Olea, Nicolás; Fernández, Mariana F.Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.
- Towards a systematic use of effect biomarkers in population and occupational biomonitoringPublication . Zare Jeddi, Maryam; Hopf, Nancy B.; Viegas, Susana; Price, Anna Bal; Paini, Alicia; van Thriel, Christoph; Benfenati, Emilio; Ndaw, Sophie; Bessems, Jos; Behnisch, Peter A.; Leng, Gabriele; Duca, Radu-Corneliu; Verhagen, Hans; Cubadda, Francesco; Brennan, Lorraine; Ali, Imran; David, Arthur; Mustieles, Vicente; Fernandez, Mariana F.; Louro, Henriqueta; Pasanen-Kase, RobertEffect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.