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Baseado no artigo publicado: Alvito P, A ssunção RM, Bajard L, Mar tins C, Mengelers M, Hans Mol, Van den Brand A, Namorado S, Vasco E, Viegas S, Silva M. Current advances, research needs and gaps in Mycotoxins Biomonitoring under HBM4EU – lessons learned and future t rends. Toxins (Basel ). 2022;14(12):826. https://doi.org/10.3390/toxins14120826 Ficheiro substituído a 2023-02-27, retificação das referências bibliográficas. As micotoxinas são toxinas naturais produzidas por fungos, apresentando efeitos tóxicos para o homem e para os animais. Reconhece-se, atualmente, que as alterações climáticas terão impacto na distribuição geográfica de algumas espécies de fungos produtores de micotoxinas o que se traduzirá, previsivelmente, num aumento da exposição humana a estes compostos. Pelas razões descritas, urge conhecer a atual exposição a micotoxinas na Europa, com vista à sua futura monitorização e à prevenção/redução do seu impacto na saúde. No âmbito da Iniciativa Europeia em Biomonitorização Humana (HBM4EU) consideraram-se as micotoxinas desoxinivalenol (DON) e fumonisina B1 (FB1) como substâncias prioritárias, tendo sido abordadas várias questões relativas à avaliação da exposição humana e o potencial risco para a saúde. No presente artigo, apresentam-se as questões identificadas como mais importantes, respostas obtidas e perspetivas futuras. Os resultados confirmaram a exposição humana a DON, tendo sido obtidos, pela primeira vez, dados harmonizados de exposição ao nível europeu e derivado um valor de referência para essa exposição. Foi ainda proposto, pela primeira vez no HBM4EU, uma sucessão de eventos biológicos baseados no mecanismo de ação da FB1 que permitiu associar a exposição durante a gravidez ao desenvolvimento de defeitos do tubo neural no feto. Espera-se que estes resultados possam contribuir para uma futura monitorização da exposição a micotoxinas na Europa e para melhorar a avaliação de risco destas substâncias. Mycotoxins are natural low-molecular-weight toxins produced by fungal species that can be toxic for humans and animals. Under the climate change scenario, some fungal species might shift their geographical distribution in response to global warming, leading to changes in the pattern of mycotoxin occurrence and, thus, increasing the risk of human mycotoxin exposure. For this reason, it urges to assess the current human exposure to mycotoxins in Europe, to monitor internal exposure and prevent future health impact. The European Human Biomonitoring Initiative (HBM4EU), running from 2017 to 2022, was set to generate knowledge on internal exposure and their potential health impacts. Within this initiative, the mycotoxins deoxynivalenol (DON) and fumonisin B1 ( FB1) were considered as priority substances to be studied and several policy questions were addressed concerning their risk assessment. The present paper presents policy questions identified within HBM4EU for these mycotoxins, answers obtained and future perspectives. The exposure of the general European population to DON was confirmed using new harmonized data and a reference guidance value for human biomonitoring was set for the first time. Additionaly, an adverse outcome pathway for neural tube defects was proposed for FB1 for the first time. Hopefully these findings may contribute to a more accurate risk assessment of European population´s exposure to mycotoxins. O projeto HBM4EU recebeu financiamento do programa de investigação e inovação da União Europeia Horizonte 2020 sob o contrato de concessão n.º 733032 e das instituições em que os autores desenvolvem as suas atividades. Os autores agradecem à FCT/MCTES pelo financiamento com fundos nacionais relativos ao CESAM (UIDP/50017/2020+UIDB/ DB/50017/2020) e ToxOmics (UIDB/00009/2020; UIDP/00009/ 2020). info:eu-repo/semantics/publishedVersion

Funding Information: Thanks are due to CESAM (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020), and ToxOmics (UIDB/00009/2020; UIDP/00009/2020), through national funds. L.B. thanks Research Infrastructure RECETOX RI (No. LM2018121), financed by the Ministry of Education, Youth and Sports, and the project CETOCOEN EXCELLENCE (No. CZ.02.1.01/0.0/0.0/17_043/0009632) for a supportive background of the European Union’s Horizon 2020 research and innovation program under grant agreement No. 857560, and to the HBM4EU, under grant agreement No. 733032. This publication reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. Funding Information: This study was co-funded by the HBM4EU, which has received funding from the European Union’s research and innovation programme Horizon 2020 under grant agreement No. 733032, and from the authors’ institutions. Publisher Copyright: © 2022 by the authors. Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB1 was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe. publishersversion published

publicado em: Environ Mol Mutagen. 2022 Aug;63(Suppl 1):88. (Abstracts from the 13th International Conference on Environmental Mutagens and 53rd Annual Meeting of the Environmental Mutagenesis and Genomics Society). https://onlinelibrary.wiley.com/toc/10982280/2022/63/S1 Human exposure to titanium dioxide nanomaterials(TiO2NMs) occurs particularly by ingestion, due to food/food contact materials and consumer products. However, the possibility of adverse effects in gastrointestinal tract is unclear. Aiming to study the impact of digestion on the NMs’ properties and their cellular/molecular effects, two human intestinal cell lines were used, Caco-2 and HT29-MTX-E12. After exposure to TiO2NMs(NM-102, NM-103, NM-105), undigested or subjected to standardized static in vitro digestion method (mimicking human digestion), the cells were analyzed for toxicity, genotoxicity, reactive oxygen species, NM uptake and intestinal translocation. We showed that in vitro digestion of TiO2NMs may increase their toxicity and DNA-damaging effect, depending on the NM, more relevant for the rutile/anatase NM-105, possibly due to its smaller hydrodynamic size in the cellular medium. Effects on chromosomal integrity were seen in HT29-MTX-E12 cells, for all tested TiO2NMs, especially after digestion. Internalization into early endosomes was confirmed for NM-103 and NM-105, before and after digestion, in monolayers of both cell lines, and at the apical membrane of polarized Caco-2 cells. The internalized NMs accumulated in late endosomes/multivesicular bodies, partially transversing the basolateral membrane of polarized Caco-2 cells without changing transepithelial electrical resistance or epithelial marker abundance. These results suggest that part of the TiO2NMs can be transcytosed through colonic epithelia without disrupting intestinal barrier integrity. Overall, the biological outcomes from TiO2NMs interaction with intestinal cells were more pronounced after digestion, highlighting its relevance in the hazard assessment of ingested NMs. Funded by FCT/MCTES through the projects: PTDC/SAU-PUB/29481/2017, UIDB/00009/2020; UIDP/00009/2020;UIDP/50017/2020+UIDB/50017/2020+LA/P/ 0094/2020; CEECIND/03143/2017 (LG), 2020.07168.BD (NV). info:eu-repo/semantics/publishedVersion

Proper nutrition in infancy and early childhood is crucial to ensuring optimal child development, growth, and better health outcomes later in life. The nutrient profile model proposed by WHO/Europe aims to assess the nutritional quality and promotional/marketing aspects of commercial baby foods aimed at children up to 36 months. We used commercial data from 191 baby foods collected between March 2021 and July 2021, from eight supermarket chains in the Lisbon Metropolitan area. According to the model specifications and the NOVA classification system, we assessed the nutritional quality and promotion aspects and the degree of processing, respectively. The presence of at least one sugar-contributing ingredient was found in 34.0% of the products; 13.9% of products listed sugars and 15.0% listed fruit juices or concentrates as an ingredient. The claim "No added sugar" was present in 69.6% of products. Only 35.1% of products comply with all the nutritional requirements of the model. Concerning processing classification, 61.8% of products were ultra-processed, and about 57.0% were indicated for children < 12 months. These findings reinforce the importance of implementing measures to ensure that commercial foods for infants are marketed appropriately and to promote foods with a lower degree of processing. publishersversion published

About Investigation of the genotoxicity of digested titanium dioxide nanomaterials in human intestinal cells This work was funded by FCT/MCTES through national funds (PIDDAC), PTDC/SAU-PUB/29481/2017 and co-funded by UID/BIM/00009/2019 (Centre for Toxicogenomics and Human Health – ToxOmics, FCT), iMed.ULisboa (PestUID/DTP/04138/2018) and CESAM (UID/AMB/50017/2019). N/A

Photosystem II is a large oxidoreductase protein complex with a crucial role in oxygenic photosynthesis where it makes use of its unique catalytic ability to facilitate water oxidation. Apart from this fundamental importance, the research on this protein has attracted extra attention over the last couple decades as PSII also serves as a paragon for the development of synthetic catalysts for solar fuel production. Consequently, great advancements have been made, with important contributions from crystallography, spectroscopy, and computational methods, so that the structure and reactive cycle of PSII is now much better understood. Although some questions remain open, like the identities of the substrate water molecules, the type of mechanism involved in the formation of the O-O bond, the proton dynamics around the reaction center of PSII, the role of structural and molecular reorganizations and the impact of special features, like red-shifted pigments in the catalytic cycle. To tackle the first question, and indirectly the second, a temperature dependent study of the interaction of ammonia, a substrate water analogue that binds directly to the Mn-cluster of PSII, was performed. From it, three possible binding spots directly to or in the close vicinity of the Mn-cluster were suggested, one of which might be a substrate water binding site. Further O2 polarography measurements of several PSII cores with unique point mutations of H-bond active residues offered a broader perspective on the protonation dynamics away from the OEC specially identing the broad channel as the most probable H+ pathway in S3→S0, with E65 as a key participant in this process. As most dynamics of the S-state cycle freeze out below 200 K, an investigation of dark-adapted PSII by means of a temperature-dependent EXAFS study identified a breakpoint in the Debye-Waller factor at this exact temperature point, revealing the importance of vibrational mobility and molecular reorganizations in the S-state transitions, which may relate to the much slower τ-value than theoretically predicted for the ET from OEC → YZ●+. Lastly, the study of PSII containing red-shifted chlorophylls showed for FRL C. thermalis a significant slowdown of the O2 release and an increase in a ΔG‡ 40 mev higher than the average value found for common PSIIs, further supporting that the reaction center of PSII from FRL C. thermalis have at least one Chl replaced by a red-shifted one., Photosystem II ist ein Schlüsselenzym der oxygenen Photosynthese, das als Oxidoreduktase die Wasserspaltung ermöglicht. Neben dieser Eigenschaft, hat das Enzym in den letzten Jahrzehnten zudem weitere Aufmerksamkeit als Vorlage für die Entwicklung synthetischer Katalysatoren für die Gewinnung von Brennstoffen mittels Sonnenenergie erhalten. Durch die Nutzung verschiedener Methoden wie Röntgenkristallographie, Spektroskopie oder Computersimulationen konnten grundlegende Erkenntnisse über dessen Funktion und Struktur gewonnen werden, wobei einige Fragen aber weiterhin offenblieben. So ist weiterhin unklar, welche Wassermoleküle als Substrat dienen, wie die O-O-Bindung im Detail erfolgt, welche Protonierungsdynamiken im Reaktionszentrum ablaufen und wie sich strukturelle und molekulare Umorientierungen im Proteinkomplex , wie z.B. die Einlagerung rot-verschobener Pigmente auf den katalytischen Zyklus auswirken. Um die ersten beiden Fragen zu adressieren, wurden im Rahmen dieser Arbeit, temperaturabhängige und zeitaufgelöste Sauerstoffmessungen mit Ammonium, einem Substratwasseranalogon, das direkt an den PSII-Mangan-Cluster bindet, durchgeführt. Diese zeigen drei Bindungsmöglichkeiten in der unmittelbaren Nähe des Mn-Clusters, mit einer als mögliche Substratwasserbindungsstelle. Weitere Sauerstoffpolarografie-Experimente mit PSII-Varianten bei denen Wasserstoffbrücken-bildende Aminosäuren ausgetauscht wurden, ermöglichten die Untersuchung der Protonierunsgdynamiken um den OEC (oxygen evolving center) und unterstützen die Hypothese, dass der breite Kanal mit E65 als Hauptprotonenweg im S3→S0 Übergang fungiert. Durch temperaturabhängige EXAFS-Studien an dunkel-adaptiertem PSII konnte ein Umschlagpunkt des Debye-Waller-Faktors bei 200 K bestimmt werden, der auch dem Temperaturpunkt entspricht, an dem der S-Zyklus zum Erliegen kommt. Diese Ergebnisse unterstützen, dass Vibrationsmobilität und molekularer Umorientierung während der S-Zyklus-Übergänge eine entscheidende Rolle spielen und in Verbindung mit dem im Vergleich zur Theorie deutlich verlangsamten τ-Wert beim Elektrontransfer vom OEC zu YZ●+ stehen könnten. Abschließende Untersuchungen an einer PSII-Variante mit rot-verschobenen Chlorophyllmolekülen, zeigte eine deutliche Verlangsamung der Sauerstofffreisetzung und eine Erhöhung in ΔG‡ um 40 meV im Vergleich zu gewöhnlichen Chlorophyll a-PSII-Varianten. Diese Unterschiede stützen die Hypothese, dass mindestens ein Chlorophyllmolekül im Reaktionszentrum durch ein rot-verschobenes Chlorophyll ersetzt wurde.

Uma nutrição saudável na infância é fundamental para o normal crescimento e desenvolvimento do bebé. Incentivar as crianças a consumir alimentos saudáveis, através de uma oferta repetida e positiva de novos alimentos, bem como limitar a sua exposição a alimentos considerados não saudáveis, podem evitar a preferências por alimentos e bebidas muito doces, contribuindo para o desenvolvimento de bons hábitos alimentares. Em 2016, a Assembleia Mundial da Saúde aprovou, através da resolução WHA69.9, o guia elaborado pela Organização Mundial de Saúde (OMS) Europa, com o objetivo de promover o fim da comercialização inadequada de alimentos para lactentes e crianças jovens. Este guia inclui uma proposta de Modelo de perfil nutricional, desenvolvido especificamente para identificar os alimentos complementares que reúnem as características adequadas para serem comercializados a crianças dos 6-36 meses, e garantir que estes mesmos são rotulados e promovidos de forma adequada. O presente estudo pretendeu avaliar a adequação nutricional dos alimentos à venda no mercado português, destinados à faixa etária dos 6-36 meses, e analisar os diferentes tipos de alegações presentes nas embalagens desses produtos. Dos 138 alimentos analisados, 69% não cumpriam todos os critérios nutricionais propostos pelo modelo da OMS. Aproximadamente 31% dos alimentos têm, pelo menos, uma fonte de açúcar indicada na lista de ingredientes. Este estudo também demonstrou que contrariamente às orientações da OMS e do Codex Alimentarius, os alimentos complementares estão a ser promovidos de forma inadequada, considerando que 97% apresentaram, pelo menos, um tipo de alegação nutricional ou de saúde na embalagem. A nível nacional, os resultados obtidos revelam a necessidade de implementar medidas que limitem a promoção de alimentos menos saudáveis destinados à faixa etária dos 6-36 meses, de modo a garantir que pais e cuidadores tenham acesso a informações claras e fiáveis sobre as escolhas alimentares que fazem para os seus filhos. Healthy nutritional choices in childhood are crucial to ensure optimal child growth and development. Encouraging infant and young children to consume healthy foods, through repeated and positive offerings of new foods, and limiting their exposure to unhealthy foods, which may influence their taste preferences for sweet foods and sugary drinks, helps to develop good feeding practices. In 2016, the World Health Assembly approved WHO Europe guidance on ending the inappropriate promotion of foods for infants and young children through resolution WHA69.9. This guidance provides a tool, in the form of a draft Nutrient profile model, specifically developed to identify commercially available complementary foods that are suitable to be marketed for infants and young children up to 36 months, and ensure that permitted products are properly labelled and promoted. The present study aimed to assess the nutritional suitability of complementary foods available on the Portuguese market, destined to the age group 6-36 months, and to analyse the different types of claims present on packages. Of the 138 complementary foods analysed, 69% did not meet all the nutritional criteria proposed by the WHO model. Approximately 31% of foods have at least one sugary source listed in the ingredients list. Contrary to guidelines issued by WHO and Codex, this study also demonstrated that complementary foods are being inappropriately promoted. Almost all products (97%) presented at least one type of nutrition or health claim on the label. The obtained results reveal the need to implement, at national level, effective preventive measures to limit the promotion of unhealthy foods marketed for infants and young children up to 36 months, in order to ensure that parents and caregivers receive clear and accurate information on complementary feeding. info:eu-repo/semantics/publishedVersion

ToR 4 Main Activity: Implementation of Nutrient Profile tools to support marketing regulations and policies on foods consumed bychildren aged below 36 months in Eurasian Economic Community (EurAsEC) and/or neighbour countries. N/A

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A exposição humana a aflatoxina B1 (AFB1) através da ingestão de alimentos contaminados e o seu impacto no trato gastrointestinal (TGI) constitui um domínio de crescente interesse científico. Para além do conhecido potencial carcinogénico, os estudos experimentais em linhas celulares, em animais e em populações humanas têm evidenciado um relevante impacto desta micotoxina no TGI, incluindo no sistema imunitário do intestino, órgão responsável por cerca de 70% das defesas do organismo. A AFB1 tem a capacidade de provocar alterações na barreira intestinal afetando o seu equilíbrio e dinâmica, o que pode induzir o aparecimento de inflamações intestinais crónicas, entre outras patologias. Estas alterações podem afetar a população em geral, contudo podem constituir uma preocupação acrescida para populações vulneráveis como grávidas e crianças, em virtude da transferência de AFB1 através da placenta. Assim, o presente trabalho tem como objetivo sensibilizar a comunidade científica para o potencial impacto da micotoxina AFB1 no intestino e contribuir para alertar e capacitar os profissionais de saúde com conhecimento científico, por forma a atuarem, da forma mais adequada, face ao eventual aumento das patologias associadas ao TGI, que poderão ocorrer em virtude do maior número de ocorrências de contaminação alimentar por AFB1, expectável como consequência das alterações climáticas. Human exposure to aflatoxin B1 (AFB1) through contaminated food ingestion and its impact on the gastrointestinal tract (GIT) is a field of scientific growing interest. In addition to the recognized carcinogenic potential, experimental studies on cell lines, animals and human populations have shown a relevant impact of this mycotoxin on GIT, including on the innate immunity of the intestine, the organ responsible for about 70% of the body's defenses. AFB1 has the ability to disrupt the intestinal barrier af fecting its balance and dynamics, and could promote the development of chronic intestinal inflammation, among other pathologies. These conditions may af fect the general population and could constitute a matter of increased concern for vulnerable populations, such as pregnant women and children, due to the AFB1 transfer across the placenta. Therefore, this study aims to sensitize the scientific community for the potential impact of the mycotoxin AFB1 in the GIT and to contribute to alert and empower the health professionals to act based on a deeper scientific knowledge, when faced with a possible increase in the number of pathologies associated to the GIT, which could occur as a result of the expected increase of food contamination by AFB1 as a consequence of climate change. Os autores agradecem à FCT/MCTES pelo financiamento com fundos nacionais relativos ao projeto earlyMYCO (PTDC/MEDTOX /28762/2017) e ao CESAM (UIDP/50017/2020+UIDB/50017/2020). R.A. agradece pelo FCT Individual CEEC 2018 Assistant Researcher Grant CEECIND/01570/2018. info:eu-repo/semantics/publishedVersion

This study was developed under the scope of WHO Collaborating Centre on Nutrition and Childhood Obesity - National Institute of Health Dr. Ricardo Jorge. Introduction: As the use of commercially available complementary foods (CACFs) has increased, it became crucial that appropriate infant feeding is protected and consumers are not mislead by statements about the composition of the product or its nutrition or health related properties. WHO published a report which proposed criteria for identifying products appropriate for promotion for infants and young children (IYC) up to 36 months. Aims: This study investigated the food claims available on CACFs and its relation with nutritional quality, using the set of criteria developed by WHO. N/A

Funding Information: This research was funded by European Food Safety Authority (EFSA) (Grant Agreement Number?GA/EFSA/AFSCO/2017/01?GA02) (The authors declare that this manuscript reflects only the authors? view and EFSA is not responsible for any use that may be made of the information it contains.). R.A., P.A. and C.M. also thanks FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 + UIDB/50017/2020), through national funds. R.A. was supported by FCT Individual CEEC 2018 Assistant Researcher Grant CEECIND/01570/2018. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Cereal-based foods, including breakfast (BC) and infant cereals (IC), are among the first solid foods introduced to infants. BC and IC are sources of macro and micronutrients that have bene-ficial effects on health, but can also be sources of harmful chemical and microbiological contaminants and nutrients that may lead to adverse health effects at high consumption levels. This study was performed under the RiskBenefit4EU project with the aim of assessing the health impact associated with consumption of BC and IC by Portuguese children under 35 months. Adverse effects associated with the presence of aflatoxins, Bacillus cereus, sodium and free sugars were assessed against the benefits of fiber intake. We applied a risk–benefit assessment approach, and quantified the health impact of changes in consumption of BC and IC from current to various alternative consumption scenarios. Health impact was assessed in terms of disability-adjusted life years. Results showed that moving from the current consumption scenario to considered alternative scenarios results in a gain of healthy life years. Portuguese children can benefit from exchanging intake of IC to BC, if the BC consumed has an adequate nutritional profile in terms of fiber, sodium and free sugars, with levels of aflatoxins reduced as much as possible. publishersversion published

publicado em: Environ Health Perspect. 2021;1. https://ehp.niehs.nih.gov/doi/abs/10.1289/isee.2021.P-473 BACKGROUND AND AIM:Mercury and its compounds are toxic and are among the substances of higher concern globally.Toxicity depends on mercury compounds, route of exposure and duration. The European population is mostly exposed to organic mercury (methylmercury) due to fish consumption; while exposure to inorganic and elemental mercury is largely associated with dental amalgams, accidental spills of elemental mercury and food produced in contaminated sites. Previous studies have shown that mercury levels in European population are higher in countries with higher fish consumption.However, because of the beneficial nutrients they provide, fish are an essential component of the human diet. In order to reduce exposure and avoid adverse health effects, it is extremely important to balance the risks and benefits of eating fish,especially in vulnerable groups such as pregnant women. Most European countries do not have official guidelines for the consumption of fish during pregnancy, and even if these guidelines exist, they are often not communicated to pregnant women in an appropriate way. As such, under the European Human Biomonitoring Initiative (HBM4EU) an intervention study – HBM4EU-MOM – is being developed in five European countries with high fish consumption (Cyprus, Greece, Iceland, Portugal, Spain) to help reduce prenatal exposure to mercury,while ensuring the nutritional benefits of fish by developing and raising awareness to specific recommendations for fish consumption during pregnancy. METHODS:This presentation will highlight the work already performed, including the harmonized development of the intervention and support materials to be implemented in the five countries. RESULTS:Preliminary results on the implementation of the developed intervention and its evaluation using Human Biomonitoring will also be presented. CONCLUSIONS:This study's results will support the definition of policies to protect human health in vulnerable populations. HBM4EU has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032. HBM4EU is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement Nº 733032. info:eu-repo/semantics/publishedVersion