Browsing by Author "Silva, Maria Joao"
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- Aula 4: Estudos de Biomonitorização HumanaPublication . Louro, Henriqueta; Silva, Maria Joao1. Biomonitorização humana e Tipos de Biomarcadores 2. Exemplo de Aplicação: biomonitorização da exposição humana a fumo de tabaco ambiental em contexto ocupacional 3. A Iniciativa Europeia de Biomonitorização (HBM4EU) 4. Conclusões
- Biological impact of metal nanomaterials in relation to their physicochemical characteristicsPublication . Louro, Henriqueta; Saruga, Andreia; Santos, Joana; Pinhão, Mariana; Silva, Maria JoaoSeveral metal and metal oxide nanomaterials (NMs), e.g., cerium dioxide NMs(CeO2), barium sulphate NMs(BaSO4) and titanium dioxide NMs(TiO2), display advantageous properties over the bulk materials and have a broad range of innovative applications in food, industry and consumer products. Whether these materials are hazardous and impact on human health or the environment remains an issue that needs to be addressed by reliable studies focused on nano-bio interactions. To contribute to the comprehensive investigation of the toxicological effects of metal NMs, we have assessed the cytotoxic and genotoxic effects of benchmark NMs in human respiratory cells, concomitantly with the analysis of their secondary properties in the cellular moiety. This study shows no effects of BaSO4, while some, but not all, of the other metal-related NMs analyzed have adverse effects. Human respiratory cells were prone to CeO2 cytotoxicity and to DNA damage induction following exposure to anatase TiO2 (NM-100, NM-101 and NM-102), but not rutile TiO2. No clastogenic/aneugenic effects were ascribed to any of the tested NMs. Using correlation analysis, this work also suggests that among these TiO2, the size in the cellular moiety may be the most relevant secondary feature that determines their biological consequences.
- Challenges of the Application of In Vitro Digestion for Nanomaterials Safety AssessmentPublication . Vital, Nádia; Gramacho, Ana Catarina; Silva, Mafalda; Cardoso, Maria; Alvito, Paula; Kranendonk, Michel; Silva, Maria Joao; Louro, HenriquetaConsidering the increase in the production and use of nanomaterials (NM) in food/feed and food contact materials, novel strategies for efficient and sustainable hazard characterization, especially in the early stages of NM development, have been proposed. Some of these strategies encompass the utilization of in vitro simulated digestion prior to cytotoxic and genotoxic assessment. This entails exposing NM to fluids that replicate the three successive phases of digestion: oral, gastric, and intestinal. Subsequently, the resulting digestion products are added to models of intestinal cells to conduct toxicological assays, analyzing multiple endpoints. Nonetheless, exposure of intestinal cells to the digested products may induce cytotoxicity effects, thereby posing a challenge to this strategy. The aim of this work was to describe the challenges encountered with the in vitro digestion INFOGEST 2.0 protocol when using the digestion product in toxicological studies of NM, and the adjustments implemented to enable its use in subsequent in vitro biological assays with intestinal cell models. The adaptation of the digestion fluids, in particular the reduction of the final bile concentration, resulted in a reduced toxic impact of digestion products.
- Evaluation of the cyto- and genotoxicity of two types of cellulose nanomaterials using human intestinal cells and in vitro digestion simulationPublication . Vital, Nádia; Cardoso, Maria; Kranendonk, Michel; Silva, Maria Joao; Louro, HenriquetaEmerging cellulose nanomaterials (CNMs) may have commercial impacts in multiple sectors, being their application particularly explored in the food sector. Thus, their potential adverse effects in the gastrointestinal tract should be evaluated before marketing. This work aimed to assess the safety of two CNMs (CNF–TEMPO and CMF–ENZ) through the investigation of their cytotoxicity, genotoxicity (comet and micronucleus assays), and capacity to induce reactive oxygen species in human intestinal cells, and their mutagenic effect using the Hprt gene mutation assay. Each toxicity endpoint was analysed after cells exposure to a concentration-range of each CNM or to its digested product, obtained by the application of a standardized static in vitro digestion method. The results showed an absence of cytotoxic effects in intestinal cells, up to the highest concentration tested (200 µg/mL or 25 µg/mL, for non-digested and digested CNMs, respectively). Of note, the cytotoxicity of the digestion control limited the top concentration of digested samples (25 µg/mL) for subsequent assays. Application of a battery of in vitro assays showed that CNF–TEMPO and CMF–ENZ do not induce gene mutations or aneugenic/clastogenic effects. However, due to the observed DNA damage induction, a genotoxic potential cannot be excluded, even though in vitro digestion seems to attenuate the effect. The lowest digested CNF–TEMPO concentration induced chromosomal damage in Caco-2 cells, leading to an equivocal outcome. Ongoing research on epigenotoxic effects of these CNMs samples may strengthen the lines of evidence on their safety when ingested, paving the way for their innovative application in the food industry.
- Exposição Humana a Micotoxinas: biomonitorização humana e contribuição para a avaliação de risco da população europeiaPublication . Alvito, Paula; Silva, Maria JoaoAs populações estão expostas diariamente a uma mistura complexa de substâncias químicas maioritariamente através da alimentação. Por forma a avaliar a exposição humana a estes contaminantes, é importante efetuar a sua biomonitorização, isto é, detetar a sua presença diretamente em amostras biológicas como sangue, cabelo, urina ou leite materno, ou prever precocemente os seus efeitos no organismo, com vista a reduzir a exposição aos químicos e contribuir para melhorar a saúde pública. A Iniciativa HBM4EU (European Human Biomonitoring Iniciative) é um consórcio europeu que conta com a participação de 30 países, da Agência Europeia do Ambiente e da Comissão Europeia, e tem por objetivo utilizar a biomonitorização humana para avaliar a exposição humana a substâncias químicas, com vista a uma melhor compreensão dos impactos associados na saúde e à melhoria da avaliação dos riscos químicos. Um dos contaminantes químicos estudados neste projeto europeu são as micotoxinas, compostos naturais produzidos por fungos e presentes maioritariamente em alimentos.
- Hazard identification and characterization of leachable chemicals from plastic products – a new PARC projectPublication . Dirven, Hubert; Bogusz, Aleksandra; Hans Bouwmeester; Busch, Mathias; Duflos, Guillaume; Eriksen, Gunnar S.; Fardilha, Margarida; Flores-Gomez, Daniela; Franko, Nina; Gaté, Laurent; Guichard, Yves; Silva, Maria Joao; Kamstra, Jorke H.; Kasiotis, Konstantinos M.; Kim, Sunmi; Kim, Young Jun; Kim, Youngsam; van der Koogh, Elise; Loureiro, Susana; Louro, Henriqueta; Machera, Kyriaki; Pieters, Raymond H. H.; Spyropoulou, Anastasia; Tzanetou, Evangelia N.; Malheiro, Catarina; Ravnjak, Tim; Repetto, Guillermo; Rivière, Gilles; Ryu, Chang Seon; Papadopoulou, Evgenia Anna; Aliferis, Konstantinos A.; Solhaug, Anita; Sollner Dolenc, Marija; Štampar, Martina; Tavares, Ana M.; Tollefsen, Knut Erik; Ventura, Célia; Walkowiak, Radoslaw; Zobl, Walter; Žegura, Bojana; Snapkow, Igor; Herzke, DorteA recent study has suggested that plastics may contain more than 16,000 chemicals, including additives, processing aids, starting substances, intermediates and Non-Intentionally Added Substances. Plastic chemicals are released throughout the plastic life cycle, from production, use, disposal and recycling. Most of these chemicals have not been studied for potential hazardous properties for humans and in the environment. To refine the risk assessment of these leachable chemicals, additional hazard data are needed. The PlasticLeach project within the EU co-funded Partnership for the Assessment of Risks from Chemicals (PARC) aims to address this data gap by screening several plastic products in daily use. Leachates will be prepared from a number of these plastic items, and these chemical mixtures will be further tested using several test guideline compliant assays and New Approach Methodologies covering both human health and environmental endpoints. The most toxic leachates will be characterized using a non-targeted analysis pipeline to identify chemicals in the leachate. When single chemicals of concern are identified, these will be further tested to determine hazardous properties and identify the respective potency factors to better understand their specific hazard profiles. A tiered approach for hazard testing will be followed. The experimental work will be complemented by toxicological profiling, using publicly available toxicity databases and tools, including Artificial Intelligence tools that cover both human and environmental endpoints. A comprehensive array of endpoints, including cytotoxicity, endocrine disruption, genotoxicity, immunotoxicity, reproductive toxicity and effects related to ecotoxicity will be evaluated. In this paper, we outline the plastic products to be tested and the battery of assays that will be used to identify hazards relevant to both human health and the environment. Data generated from approaches will be reported using standardized formats, stored within a centralized repository, and harmonized to adhere to the FAIR data principles (Findable, Accessible, Interoperable, and Reusable). This integrated strategy will not only advance our understanding of the risks associated with plastic-derived chemicals but will also provide critical support for regulatory decision-making and facilitate the development of safer, and more ecofriendly plastic materials in the future.
- HBM4EU chromates study: the Portuguese integrated and harmonized study on exposure to hexavalent chromium and related early effects.Publication . Viegas, Susana; Martins, Carla; Ribeiro, Edna; Ladeira, Carina; Pinhal, Hermínia; Nogueira, Ana; Santos, Sílvia; Tavares, Ana; Gomes, Bruno Costa; Afonso, Catarina Maia; Louro, Henriqueta; Silva, Maria JoaoIn the scope of the European Union (EU) human biomonitoring initiative, a multicentric study on different occupational settings from several European countries was performed, to provide information on occupational exposure to hexavalent chromium [Cr(VI)], a known lung carcinogen. Biomonitoring approaches were used to obtain exposure data to support the implementation of new risk management measures and policy actions at the national and European levels. This work describes the Portuguese contribution to the study, which aimed to assess workers' exposure to Cr, by using exposure biomarkers (urinary chromium [U-Cr]), and industrial hygiene samples (air and hand wipes) and to link exposure to potential long-term health effects by using effect biomarkers. Exposure determinants influencing exposure were explored from the contextual information and human biomonitoring data. The ultimate goal of the study was to appraise the risk management measures contributing to minimize exposure and protect workers' health. Several occupational settings and activities were considered, including plating, welding, and painting. A control group from the Portuguese general population was also included. Data on age, sex, and smoking habits from both groups were considered in the statistical analysis. Information on the risk management measures available for workers was collected and used to identify the ones that mainly contributed to reduce exposure. Environmental monitoring and human biomonitoring revealed that painters were the highest exposed group. The use of respiratory protection equipment showed an influence on total U-Cr levels for workers involved in painting activities. Concerning early health effects, the painters presented also a significantly higher level of DNA and chromosomal damage in peripheral blood cells, as compared to the control group, suggesting a plausible association between exposure to Cr(VI) and early genotoxic effects. The results showed that workers are exposed to Cr(VI) in those occupational settings. These findings point to the need to improve the prevention and risk management measures and the implementation and enforcement of new regulatory actions at the national level.
- New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) projectPublication . Snapkow, Igor; Smith, Nicola M.; Arnesdotter, Emma; Beekmann, Karsten; Blanc, Etienne B.; Braeuning, Albert; Corsini, Emanuela; Sollner Dolenc, Marija; Duivenvoorde, Loes P.M.; Sundstøl Eriksen, Gunnar; Franko, Nina; Galbiati, Valentina; Gostner, Johanna M.; Grova, Nathalie; Gutleb, Arno C.; Hargitai, Rita; Janssen, Aafke W.F.; Krapf, Solveig A.; Lindeman, Birgitte; Lumniczky, Katalin; Maddalon, Ambra; Mollerup, Steen; Parráková, Lucia; Pierzchalski, Arkadiusz; Pieters, Raymond H.H.; Silva, Maria Joao; Solhaug, Anita; Staal, Yvonne C.M.; Straumfors, Anne; Szatmári, Tünde; Turner, Jonathan D.; Vandebriel, Rob J.; Zenclussen, Ana Claudia; Barouki, RobertAs a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties. Due to this limitation, various authorities, including the World Health Organization and the European Food Safety Authority have highlighted the need for the development of novel approaches without the use of animals for immunotoxicity testing of chemicals. In this paper, we present a concise overview of ongoing efforts dedicated to developing and standardizing methodologies for a comprehensive characterization of the immunotoxic effects of chemicals, which are performed under the EU-funded Partnership for the Assessment of Risk from Chemicals (PARC).
- Physiologically based toxicokinetic models in aggregate exposure: A reviewPublication . Lamon, L.; Paini, A.; Siccardi, M.; Doyle, J.; McNamara, C.; Galea, K.S.; Ghosh, M.; Louro, Henriqueta; Silva, Maria Joao; El Yamani, N.; Dusinska, M.; Moeller, R.; Duca, R.C.; Cubadda, F.; Viegas, S.; Martins, C.; Price, P.This literature review explores the application of Physiologically Based Kinetic (PBK) models in aggregate exposure (AE) assessment across different chemical classes. It builds on the screening of 1119 publications and the identification of 40 relevant articles. The most frequently studied chemicals include volatile organic compounds and plant protection products, with metals, personal care products, persistent organic pollutants and plasticisers also represented. Most studies reported in this review are applied to human populations and build on human biomonitoring (HBM) data to enhance model reliability. However, some studies use animal models (primarily rat models) and apply cross-species extrapolation to the human AE scenario. Occupational exposure is taken into consideration as part of the AE scenario in a few studies. Many of the reviewed studies are designed in support of chemical risk assessment (CRA), illustrating the wide applicability of PBK models. The review discusses the joint role of HBM data and PBK model in AE scenarios, highlighting its importance for a reliable risk assessments. The studies identified and discussed in this review suggest a broad interpretation of AE. The diversity across case reported studies is attributed to varying interpretations and existing definitions of AE. Finally, the roles of forward and reverse dosimetry in refining AE assessments are discussed, highlighting their importance for future research. This scoping review provides a comprehensive overview of PBK model applications in addressing AE, serving as a valuable foundation for future research and development aimed at advancing human health protection towards the Next-Generation Risk Assessment (NGRA).
- Safety assessment of the substances ‘wax, rice bran, oxidised’ and ‘wax, rice bran, oxidised, calcium salt’ for use in food contact materialsPublication . EFSA Panel on Food Contact Materials; Lambré, C.; Crebelli, R.; Silva, Maria Joao; Grob, K.; Lampi, E.; Milana, M.R.; Pronk, M.; Ščetar, M.; Theodoridis, G.; Van Hoeck, E.; Waegeneers, N.; Bolognesi, C.; Cariou, R.; Castle, L.; Di Consiglio, E.; Franz, R.; Barthélémy, E.; Comandella, D.; Rivière, G.The EFSA Panel on Food Contact Materials (FCM) assessed the safety of the substances ‘wax, rice bran, oxidised’ and ‘wax, rice bran, oxidised, calcium salt’, used as additives up to 0.3% in polyethylene terephthalate (PET), polyamide (PA), thermoplastic polyurethane (TPU), polylactic acid (PLA) and poly(vinyl chloride) (PVC) in contact with all food types for long‐term storage at room temperature and below, after hot‐fill and/or heating. The substances consist of the chemical classes wax esters, carboxylic acids, alcohols and calcium salts of acids, along with an unidentified organic fraction up to w/w. Migration into 10% ethanol and 4% acetic acid was below 0.012 mg/kg for each chemical class, and about 0.001 mg/kg for the unidentified fraction. In isooctane, migration was up to 0.297 mg/kg food for wax esters, below 0.01 mg/kg food for the other chemical classes and about 0.02 mg/kg food for the unidentified fraction. The contact with dry food and food simulated by 20% ethanol were considered covered by the migration tests with aqueous simulants. Based on genotoxicity assays and compositional analyses, the constituents of the chemical classes did not raise a concern for genotoxicity. The potential migration of individual constituents or groups of chemically‐related compounds of the unidentified fraction would result in exposures below (for aqueous food) and above (for fatty food) the threshold of toxicological concern for genotoxic carcinogens. Therefore, the FCM Panel concluded that the substances are not of safety concern for the consumer, if used as additives up to 0.3% w/w in PET, PLA and rigid PVC materials and articles intended for contact with all food types except for fatty foods, for long‐term storage at room temperature and below, including hot‐fill and/or heating up to 100°C for up to 2 h.