Browsing by Author "Borges, Teresa"
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- Avaliação do risco de crianças expostas a micotoxinas através do consumo de cereais de pequeno-almoçoPublication . Borges, Teresa; Alvito, Paula
- Contribution to nanomaterials safety assessment: the need of integrating in vitro, in vivo and in silico strategiesPublication . Silva, Maria João; Louro, Henriqueta; Borges, Teresa; Lavinha, João; Albuquerque, José MariaFundamental and application-driven research in nanotechnology is expected to boost nanoscience and innovation towards development of safe-by-design nanomaterials(NM). In this scenario, adding vast societal benefits, a multi-disciplinary approach to responsible innovation must be undertaken. Although the widespread use of NM, it is not clear whether they impact on environment and human health, on the long-term. Potential deleterious effects, e.g., genotoxicity that is intimately associated with carcinogenicity, have to be assessed using complementary in vitro and in vivo assays, nested within the conventional risk assessment paradigm and considering specific physicochemical properties of NM. In this study we present the testing strategy that was recently applied to the genotoxicity characterization of titanium dioxide nanomaterials in human cells and in an integrative in vivo model. The results supported the view that a thorough understanding of the relationship between the physicochemical properties, the behaviour of NM in biological systems and their mechanism of action is of utmost importance to predict their biological activity. In conclusion, the knowledge gap between nanoscience and hazard assessment has to be filled within a multi-disciplinary approach including experimental and computational components in an iterative process, towards an improved strategy for the safety evaluation of nanomaterials.
- Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014-2021)Publication . Govarts, Eva; Gilles, Liese; Rodriguez Martin, Laura; Santonen, Tiina; Apel, Petra; Alvito, Paula; Anastasi, Elena; Andersen, Helle Raun; Andersson, Anna-Maria; Andryskova, Lenka; ANTIGNAC, Jean-Philippe; Rüther, Maria; Sarigiannis, Denis; Silva, Maria João; Šlejkovec, Zdenka; Snoj Tratnik, Janja; Stajnko, Anja; Szigeti, Tamas; Tarazona, Jose; Thomsen, Cathrine; Tkalec, Žiga; Trnovec, Tomas; Tolonen, Hanna; Uhl, Maria; Van Nieuwenhuyse, An; Vasco, Elsa; Verheyen, Veerle J.; Viegas, Susana; Vinggaard, Anne Marie; Vogel, Nina; Vorkamp, Katrin; Wasowicz, Wojciech; Wimmerova, Sona; Weber, Till; Woutersen, Marjolijn; Zimmermann, Philipp; Zvonar, Martin; Koch, Holger; Kolossa-Gehring, Marike; Esteban López, Marta; Castano, Argelia; Stewart, Lorraine; Sepai, Ovnair; Appenzeller, Brice; Schoeters, Greta; Barbone, Fabio; Barnett-Itzhaki, Zohar; Barouki, Robert; Berman, Tamar; Bil, Wieneke; Borges, Teresa; Buekers, Jurgen; Cañas-Portilla, Ana; Covaci, Adrian; Csako, Zsofia; Den Hond, Elly; Dvorakova, Darina; Fabelova, Lucia; Fletcher, Tony; Frederiksen, Hanne; Gabriel, Catherine; Ganzleben, Catherine; Göen, Thomas; Halldorsson, Thorhallur; Haug, Line Småstuen; Horvat, Milena; Huuskonen, Pasi; Imboden, Medea; Jagodic Hudobivnik, Marta; Janasik, Beata; Janev Holcer, Natasa; Karakitsios, Spyros; Katsonouri, Andromachi; Klanova, Jana; Kokaraki, Venetia; Kold Jensen, Tina; Koponen, Jani; Laeremans, Michelle; Laguzzi, Federica; Lange, Rosa; Lemke, Nora; Lignell, Sanna; Lindroos, Anna Karin; Lobo Vicente, Joana; Luijten, Mirjam; Makris, Konstantinos C.; Mazej, Darja; Melymuk, Lisa; Meslin, Matthieu; Mol, Hans; Montazeri, Parisa; Murawski, Aline; Namorado, Sónia; Niemann, Lars; Nübler, Stefanie; Nunes, Baltazar; Olafsdottir, Kristin; Palkovicova Murinova, Lubica; Papaioannou, Nafsika; Pedraza-Diaz, Susana; Piler, Pavel; Plichta, Veronika; Poteser, Michael; Probst-Hensch, Nicole; Rambaud, Loic; Rauscher-Gabernig, Elke; Rausova, Katarina; Remy, Sylvie; Riou, Margaux; Rosolen, Valentina; Rousselle, ChristopheAbstract: As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.
- How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EUPublication . Santonen, Tiina; Mahiout, Selma; Alvito, Paula; Apel, Petra; Bessems, Jos; Bil, Wieneke; Borges, Teresa; Bose-O'Reilly, Stephan; Buekers, Jurgen; Cañas Portilla, Ana Isabel; Calvo, Argelia Castaño; de Alba González, Mercedes; Domínguez-Morueco, Noelia; López, Marta Esteban; Falnoga, Ingrid; Gerofke, Antje; Caballero, María del Carmen González; Horvat, Milena; Huuskonen, Pasi; Kadikis, Normunds; Kolossa-Gehring, Marike; Lange, Rosa; Louro, Henriqueta; Martins, Carla; Meslin, Matthieu; Niemann, Lars; Díaz, Susana Pedraza; Plichta, Veronika; Porras, Simo P.; Rousselle, Christophe; Scholten, Bernice; Silva, Maria João; Šlejkovec, Zdenka; Tratnik, Janja Snoj; Joksić, Agnes Šömen; Tarazona, Jose V.; Uhl, Maria; Van Nieuwenhuyse, An; Viegas, Susana; Vinggaard, Anne Marie; Woutersen, Marjolijn; Schoeters, GreetThe need for such information is pressing, as previous research has indicated that regulatory risk assessors generally lack knowledge and experience of the use of HBM data in RA. By recognising this gap in expertise, as well as the added value of incorporating HBM data into RA, this paper aims to support the integration of HBM into regulatory RA. Based on the work of the HBM4EU, we provide examples of different approaches to including HBM in RA and in estimations of the environmental burden of disease (EBoD), the benefits and pitfalls involved, information on the important methodological aspects to consider, and recommendations on how to overcome obstacles. The examples are derived from RAs or EBoD estimations made under the HBM4EU for the following HBM4EU priority substances: acrylamide, o-toluidine of the aniline family, aprotic solvents, arsenic, bisphenols, cadmium, diisocyanates, flame retardants, hexavalent chromium [Cr(VI)], lead, mercury, mixture of per-/polyfluorinated compounds, mixture of pesticides, mixture of phthalates, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), and the UV-filter benzophenone-3. Although the RA and EBoD work presented here is not intended to have direct regulatory implications, the results can be useful for raising awareness of possibly needed policy actions, as newly generated HBM data from HBM4EU on the current exposure of the EU population has been used in many RAs and EBoD estimations.
- Human biomonitoring in health risk assessment in Europe: current practices and recommendations for the futurePublication . Louro, Henriqueta; Heinälä, Milla; Bessems, Jos; Buekers, Jurgen; Vermeire, Theo; Woutersen, Marjolijn; van Engelen, Jacqueline; Borges, Teresa; Rousselle, Christophe; Ougier, Eva; Alvito, Paula; Martins, Carla; Assunção, Ricardo; Silva, Maria João; Pronk, Anjoeka; Schaddelee-Scholten, Bernice; Del Carmen Gonzalez, Maria; de Alba, Mercedes; Castaño, Argelia; Viegas, Susana; Humar-Juric, Tatjana; Kononenko, Lijana; Lampen, Alfonso; Vinggaard, Anne Marie; Schoeters, Greet; Kolossa-Gehring, Marike; Santonen, TiinaHuman biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).
- Is there a link between the physicochemical characteristics of multiwalled carbon nanotubes and their genotoxicity in human cells?Publication . Louro, Henriqueta; Pinhão, Mariana; Tavares, Ana; Vital, Nádia; Borges, Teresa; Gouveia, Helena; Silva, Maria JoãoThe wide applicability of manufactured nanomaterials (NM) has led to an increased risk of human exposure and environmental dissemination. In particular, multi-walled carbon nanotubes (MWCNT) have been developed for industrial purposes, but the same properties that render these materials so attractive may also cause higher toxicity. However, contradictory results concerning their genotoxicity and carcinogenicity have been reported, suggesting that minor changes in physicochemical properties may determine their toxicity. The objective of this work was to characterize the cyto- and genotoxic effects of MWCNTs that differ in thickness, length and aspect ratio (NM-401, NM-402 and NM-403, JRC repository) in human-derived bronchial epithelial cells (BEAS-2B), in order to ascertain which characteristic(s) may be determinant for their genotoxicity. After NM dispersion using a standardized protocol, cell cultures were exposed to several NM concentrations (0-256 μg/ml). Cell viability was evaluated by the Trypan blue dye exclusion assay. For genotoxicty testing, a combination of the alkaline comet assay (3- or 24h- exposure) and the cytokinesis-blocked micronucleus assay (48h-exposure) was used. The results showed that NM-401 and NM-403 were cytotoxic following 24h exposure, whereas the highest doses of NM-402 were cytotoxic at 3h. The genotoxicity results in relation to the different MWCNT tested were not consistent, indicating that diameter and length are rather important properties that influence the genotoxic potential of these NM. In summary, our work confirmed that the standard genotoxicity tests can be applied for evaluating the genotoxicity of different types of MWCNT. However, we also concluded that specific physicochemical properties impact on the genotoxic potential of these high aspect ratio NM, an issue that has to be further understood, possibly by targeted testing. Regarding safety assessment and related regulatory aspects, the differential genotoxicity observed for closely related NM highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NM.
- Moving towards a safe by design approach for ENM: linking ENM relevant properties to toxicological concernsPublication . Borges, Teresa; Silva, Maria João; Louro, HenriquetaWithin the Safe by Design concept, the functionality of a material and its toxicity are considered in an integrated way. The central goal of this presentation is to discuss some fundamental principles of engineered nanomaterials (ENM) interactions with biological systems relevant to human exposure and biological responses. Major factors to consider in the ENM safe-by-design approach are surface modification to reduce the potential hazardous properties of target nanoparticles (NP), compatibility between NP coatings and their matrix, as well as biopersistence, considering the relevant exposure scenarios across the life cycle of the target NP and products. This is a cross-disciplinary field that needs to identify, at earlier stages of the ENM R&D process, the physicochemical properties that may act as good predictors of toxicity, e.g. crystal structure/reactivity, zeta potential/surface charge/dynamic properties. Furthermore, it is also needed to build adequate screening in vitro testing strategies (realistic doses, exposure duration and target tissues), incorporating relevant hazard endpoints that can give an insight about the toxicological mode of action (MoA) with relevance to human health and environment, taking into account the uses and applications along the lifecycle (EHS roadmap). These topics will be illustrated by a cytotoxicity and genotoxicity study performed with a set of ENM with identical chemistry but different physicochemical characteristics that highlighted the importance of investigating each ENM individually, instead of assuming a common MoA. The findings, although creating a dilemma for developing criteria for categorization and read-across, are also suggestive of the importance of considering the functionality of a material and its toxicity in an integrated way, enabling a safe-by-design concept. Ultimately, the overall safety data is intended to best support the decision of IND developers and risk managers during the ENM design and development processes.
- Moving towards a safe-by-design approach for ENM: linking relevant properties to safetyPublication . Borges, Teresa; Silva, Maria João; Louro, HenriquetaOral Communication - Topic points: safe-by-design in the context of ENM; the main pillars of SbD: LCA and risk assessment; how design may influence quality and safety of nano-enabled products
- Nanomateriais manufaturados: novos desafios para a saúdePublication . Louro, Henriqueta; Borges, Teresa; Silva, Maria JoãoOs nanomateriais manufaturados (NM)apresentam propriedades físico-químicas específicas que lhes conferem caraterísticas mecânicas, óticas, elétricas e magnéticas únicas e vantajosas para aplicações industriais e biomédicas. Contudo, o desenvolvimento exponencial das nanotecnologias contrasta com a ainda insuficiente avaliação de risco para a saúde humana e para o ambiente, conduzindo a preocupações em termos de saúde pública. Esta revisão procura sintetizar o conhecimento atual sobre a toxicidade dos NM, identificar as lacunas ainda existentes e descrever o contributo da nanotoxicologia para o enquadramento regulamentar dos NM, de modo a garantir a sua utilização segura e a minimização dos riscos para a saúde pública.
- Perceções da população portuguesa sobre biomonitorização humana segundo o inquérito aos cidadãos do HBM4EUPublication . Namorado, Sónia; Louro, Henriqueta; Isidro, Glória; Cavaleiro, Rita; Moura, Isabel; Borges, Teresa; Virgolino, Ana; Santos, Osvaldo; Vicente, Joana Lobo; Silva, Maria JoãoNo âmbito da Iniciativa Europeia em Biomonitorização Humana (HBM4EU) foi realizado um inquérito dirigido aos cidadãos europeus que pretendia recolher informação acerca das suas opiniões e perceções sobre a exposição a substâncias químicas, bem como sobre o que é a biomonitorização humana (BMH), por que é que ela é importante e qual o seu papel na saúde. Em Portugal responderam ao inquérito 669 indivíduos, a maioria do sexo feminino, com ensino superior e empregados. A maioria dos participantes portugueses considera que a BMH é uma atividade que deve ser realizada regularmente e de forma coordenada. Os participantes também consideram que os estudos de BMH são muito relevantes para várias atividades, desde a avaliação do impacto da exposição às substâncias químicas, ao apoio de políticas de saúde ocupacional. As áreas indicadas como uma prioridade para os estudos de BMH revelaram uma maior preocupação com a exposição por via alimentar.