Browsing by Author "Vogel, Ulla"
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- Aplicação da biomonitorização humana para avaliação da exposição ocupacional a hidrocarbonetos aromáticos policíclicos na Europa: uma revisão da literaturaPublication . Louro, Henriqueta; Gomes, Bruno Costa; Saber, Anne Thoustrup; Iamiceli, Anna Laura; Göen, Thomas; Jones, Kate; Katsonouri, Andromachi; Neophytou, Christiana; Vogel, Ulla; Ventura, Célia; Oberemm, Axel; Duca, Radu Corneliu; Fernandez, Mariana F.; Olea, Nicolas; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoOs hidrocarbonetos aromáticos policíclicos (HAPs) são produtos químicos com impacto em saúde ocupacional, pelo que a avaliação da exposição humana através de estudos de biomonitorização tem aumentado nos últimos anos. No entanto, os dados obtidos são ainda insuficientes para os reguladores e decisores políticos. Este trabalho, no contexto da Iniciativa Europeia em Biomonitorização Humana (HBM4EU), descreve uma revisão da literatura sobre a exposição ocupacional aos HAPs na Europa, entre 2008 e 2022, com o objetivo de identificar as vantagens e limitações dos vários biomarcadores de exposição e /ou de efeito, bem como o conhecimento em falta para melhorar a regulamentação. Os resultados da análise dos 42 artigos elegíveis para inclusão nesta revisão demonstram que o biomarcador de exposição mais utilizado é o 1-hidroxipireno urinário, sendo os biomarcadores de efeito mais comuns, biomarcadores de stresse oxidativo e genotoxicidade. Globalmente, verificou-se a necessidade de desenvolver novas abordagens de recolha de dados e amostras, bem como a seleção apropriada de biomarcadores de forma a obter dados fiáveis e comparáveis em diferentes setores industriais. Além disso, a aplicação de biomarcadores de efeito contribui para a identificação de ambientes de trabalho ou atividades de alto risco, possibilitando medidas de mitigação e gestão de risco.
- Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledgePublication . Rodríguez-Carrillo, Andrea; Mustieles, Vicente; Salamanca-Fernández, Elena; Olivas-Martínez, Alicia; Suárez, Beatriz; Bajard, Lola; Baken, Kirsten; Blaha, Ludek; Bonefeld-Jørgensen, Eva Cecilie; Couderq, Stephan; D'Cruz, Shereen Cynthia; Fini, Jean-Baptiste; Govarts, Eva; Gundacker, Claudia; Hernández, Antonio F.; Lacasaña, Marina; Laguzzi, Federica; Linderman, Birgitte; Long, Manhai; Louro, Henriqueta; Neophytou, Christiana; Oberemn, Axel; Remy, Sylvie; Rosenmai, Anna Kjerstine; Saber, Anne Thoustrup; Schoeters, Greet; Silva, Maria João; Smagulova, Fatima; Uhl, Maria; Vinggaard, Anne Marie; Vogel, Ulla; Wielsøe, Maria; Olea, Nicolás; Fernández, Mariana F.Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.
- Nanomaterials versus ambient ultrafine particles: an opportunity to exchange toxicology knowledgePublication . Stone, Vicki; Miller, Mark R.; Clift, Martin J.D.; Elder, Alison; Mills, Nicholas L.; Møller, Peter; Schins, Roel P.F.; Vogel, Ulla; Kreyling, Wolfgang G.; Alstrup Jensen, Keld; Kuhlbusch, Thomas A.J.; Schwarze, Per E.; Hoet, Peter; Pietroiusti, Antonio; De Vizcaya-Ruiz, Andrea; Baeza-Squiban, Armelle; Teixeira, João Paulo; Tran, C. Lang; Cassee, Flemming R.BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa.
- The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive ReviewPublication . Louro, Henriqueta; Gomes, Bruno Costa; Saber, Anne Thoustrup; Iamiceli, Anna Laura; Göen, Thomas; Jones, Kate; Katsonouri, Andromachi; Neophytou, Christiana M.; Vogel, Ulla; Ventura, Célia; Oberemm, Axel; Duca, Radu Corneliu; Fernandez, Mariana F.; Olea, Nicolas; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoPolycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers’ health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008–2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.
- Variation in the measurement of DNA damage by comet assay measured by the ECVAG† inter-laboratory validation trialPublication . Forchhammer, Lykke; Johansson, Clara; Loft, Steffen; Möller, Lennart; Godschalk, Roger, W. L.; Langie, Sabine A. S.; Jones, George D. D.; Kwok, Rachel W. L.; Collins, Andrew R.; Azqueta, Amaya; Phillips, David H.; Sozeri, Osman; Stepnik, Maciej; Palus, Jadwiga; Vogel, Ulla; Wallin, Hakan; Routledge, Michael N.; Handforth, Catherine; Allione, Alessandra; Matullo, Giuseppe; Teixeira, João Paulo; Costa, Solange; Riso, Patrizia; Porrini, Marisa; Møller, PeterThe comet assay has become a popular method for the assessment of DNA damage in biomonitoring studies and genetic toxicology. However, few studies have addressed the issue of the noted inter-laboratory variability of DNA damage measured by the comet assay. In this study, 12 laboratories analysed the level of DNA damage in monocyte-derived THP-1 cells by either visual classification or computer-aided image analysis of pre-made slides, coded cryopreserved samples of cells and reference standard cells (calibration curve samples). The reference standard samples were irradiated with ionizing radiation (0–10 Gy) and used to construct a calibration curve to calculate the number of lesions per 106 base pair. All laboratories detected dose–response relationships in the coded samples irradiated with ionizing radiation (1.5–7 Gy), but there were overt differences in the level of DNA damage reported by the different laboratories as evidenced by an inter-laboratory coefficient of variation (CV) of 47%. Adjustment of the primary comet assay end points by a calibration curve prepared in each laboratory reduced the CV to 28%, a statistically significant reduction (P < 0.05, Levene's test). A large fraction of the inter-laboratory variation originated from differences in image analysis, whereas the intra-laboratory variation was considerably smaller than the variation between laboratories. In summary, adjustment of primary comet assay results by reference standards reduces inter-laboratory variation in the level of DNA damage measured by the alkaline version of the comet assay.