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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