Browsing by Author "Mengelers, Marcel"
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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.
- Biomonitorização humana de micotoxinas no âmbito do projeto HBM4EU: um estudo sobre desoxinivalenol e fumonisina B1Publication . Alvito, Paula; Namorado, Sónia; Assunção, Ricardo; Bajard, Lola; Martins, Carla; Mengelers, Marcel; Mol, Hans; Van den Brand, Annick; Vasco, Elsa; Viegas, Susana; Silva, Maria JoãoAs 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.
- Human biomonitoring of mycotoxins under HBM4EU: update on key outputsPublication . Alvito, Paula; Assunção, Ricardo; Bajard, Lola; Mol, Hans; Martins, Carla; Mengelers, Marcel; Namorado, Sónia; Vasco, Elsa; Van den Brand, Annick; Viegas, Susana; Silva, MariaThe European Human Biomonitoring Initiative (HBM4EU) is a project gathering 30 countries, funded under Horizon 2020 and running from 2017 until 2021. The goal of HBM4EU is to generate evidence on the current exposure of European citizens to chemicals and on their possible health effects to assess the associated risks. Following a systematic prioritization exercise, the mycotoxins Deoxynivalenol (DON) and Fumonisin B1 (FB1) were considered as priority substances around which the HBM4EU research programme was developed. As part of the HBM4EU project, several policy questions are being addressed for these mycotoxins, concerning analytical methods, exposure levels and high exposure population groups in Europe (including workers), associated time trends, risk characterization, exposure models and toxicokinetic data, human biomonitoring guidance values, key events that determine the health effects of the target mycotoxins, effect biomarkers, data gaps and research needs. Key outputs from HBM4EU achieved until now for DON and FB1, include: i) a biomarker selected to assess human exposure to DON (total urinary DON) that will be used in the aligned studies, ii) several European laboratories selected to perform DON analysis after passing an interlaboratory study, ii) a research protocol on human exposure and geographic variations in Europe, iv) a risk assessment plan to assess DON and FB1 exposure in Europe, v) a review of available toxicokinetics models, vi) a draft on the possible mechanisms of FB1-induced adverse health effects and vii) a specific effect biomarker for FB1.
- Plan for development of case studies - Deliverable Report AD 15.1 WP 15 - Mixtures, HBM and human health riskPublication . Kortemkamp, Andreas; Mengelers, Marcel; Vinggaard, Anne Marie; Silva, Maria João; Slamay, Remy; Vermeulen, Roel; Vlaanderen, Jelle; Ottenbros, Ilse; Viegas, Susana; Gomes, Bruno Costa; Louro, Henriqueta; Lebret, ErikThis deliverable describes the activities in task 15.3 leading up to the development of cases studies for mixture health effects and outlines the proposed case studies. The proposed case studies are: · Developmental neurotoxicity beyond polybrominated diphenylethers · Heavy metals and nephrotoxicity · Anti-androgenic chemicals and male reproductive health · Chromium (VI), nickel and polycyclic aromatic hydrocarbons and lung cancer · Addressing exposure misclassification in mixture studies The Addendum provides further details about multi-year perspective and timing, as well as detailed budgetary aspects per case study.