Browsing by Author "Tavares, Ana Maria"
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- Avaliação do risco da mistura de crómio hexavalente, níquel e hidrocarbonetos aromáticos policíclicos a partir de dados de exposição ocupacional extraídos da literaturaPublication . Tavares, Ana Maria; Viegas, Susana; Louro, Henriqueta; Goen, Thomas; Santonen, Tiina; Luijten, Mirjam; Kortenkamp, Andreas; Silva, Maria JoãoNa maioria dos contextos laborais ocorre, em geral, exposição a misturas de substâncias químicas. Este estudo, inserido na iniciativa HBM4EU, visou avaliar o risco de exposição a misturas de crómio hexavalente [Cr ( VI ) ], níquel (Ni ) e/ou hicrocarbonetos aromáticos policíclicos (HAPs ) a partir de dados de exposição reportados em estudos realizados em várias indústrias na Europa. Para a avaliação do risco de misturas binárias (Cr e Ni ) e ternárias (Cr, Ni e HAPs ) calcularam-se os Quocientes de Risco (QR) e a Soma dos Quocientes de Risco (SQR) a partir dos dados de biomonitorização humana (BMH) e de medições dessas substâncias no ar. É geralmente aceite que um valor de QR ou SQR superior a 1 indica um risco acrescido para a saúde. Para a maioria das medições de exposição a partir de biomarcadores urinários obtiveram-se valores médios de SQR>1, sendo que os respetivos QR calculados para cada uma das substâncias individuais por vezes não excederam os valores limite (QR<1). Estes resultados mostram não só que existe um risco acrescido para a saúde decorrente da coexposição a estas substâncias em contexto ocupacional, como também que esse risco é frequentemente subestimado no processo clássico de avaliação de risco substância a substância. Com este estudo demonstrou-se a relevância de avaliar o risco decorrente da exposição a misturas, particularmente com base em dados de BMH, sendo esta uma abordagem mais realista do contexto ocupacional e que permite uma melhor caracterização do risco com vista a uma proteção mais eficaz da saúde dos trabalhadores.
- Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B1 in human kidney and liver cell modelsPublication . Pinhão, Mariana; Tavares, Ana Maria; Loureiro, Susana; Louro, Henriqueta; Alvito, Paula; Silva, Maria JoãoFood products can be contaminated by several fungi species and each species may produce different mycotoxins, leading to human combined exposure. Although predictions about the joint toxic effects of mycotoxins can be made from their individual toxicities, experimental data is still limited to allow a reliable hazard assessment. Thus, this study aimed to characterize the combined cytotoxic and genotoxic effects of ochratoxin A (OTA) and fumonisin B1 (FB1) in cell lines representative of their target organs, kidney and liver. Interactions were ascertained using mathematical extensions to the reference models of concentration addition and independent action. Cytotoxicity (MTT assay) data modeling revealed a synergistic pattern for low doses of both FB1 and OTA shifting to antagonism at higher concentration levels, irrespectively of the reference model applied. Concerning genotoxicity assessment, neither OTA nor FB1, individually or in combination, induced a prominent increase in DNA damage (comet assay) or oxidative DNA damage (FPG-comet assay). In conclusion, this study revealed a synergistic cytotoxic effect for OTA and FB1 at low concentration levels. Given that human co-exposure to these two mycotoxins is probable to occur at low doses, these results raise concerns regarding their potential health outcomes that seem to differ from those predicted by an additive model.
- O ensaio do micronúcleo em células da mucosa bucal: aplicabilidade em biomonitorização humanaPublication . Rosário, Rita Lopes; Tavares, Ana Maria; Louro, Henriqueta; Silva, Maria JoãoAs exposições ambientais e ocupacionais a alguns agentes químicos ou físicos representam sérios riscos para a saúde humana. A biomonitorização humana (BMH) permite quantificar a exposição a substâncias químicas e seus efeitos precoces através da caracterização de biomarcadores de exposição e de biomarcadores de efeito. O ensaio do micronúcleo em células bucais (MNBMCyt) é um biomarcador precoce de genotoxicidade que permite identificar instabilidade cromossómica em células da mucosa oral, tendo vindo a encontrar uma aplicação crescente em estudos de BMH. Nesta revisão pretendeu-se dar uma perspetiva da aplicação do MNBMCyt em estudos epidemiológicos realizados em contexto ambiental e ocupacional, com base em exemplos de estudos de BMH recolhidos através de pesquisa bibliográfica. Globalmente, a facilidade da colheita e processamento da amostra, aliada à já existente harmonização de procedimentos de análise e à sensibilidade para deteção precoce de efeitos genotóxicos decorrentes da exposição a variados agentes químicos (p.ex., compostos orgânicos voláteis, metais, entre outros) e físicos (radiação ionizante) têm levado a propor a sua mais frequente inclusão em futuros estudos de BMH. Contudo, ainda permanecem algumas limitações analíticas (análise microscópica morosa) e necessidade de mais dados que permitam fortalecer a relevância e grau de confiança neste biomarcador, para reforçar a sua futura utilização para apoiar intervenções que visem prevenir o desenvolvimento de doenças relacionadas com a exposição a substâncias genotóxicas.
- Estudos da toxicidade de misturas de aflatoxina M1 e ocratoxina A numa linha celular humanaPublication . Tavares, Ana Maria; Alvito, Paula; Loureiro, Susana; Louro, Henriqueta; Silva, Maria João
- Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytesPublication . Tavares, Ana Maria; Louro, Henriqueta; Antunes, Susana; Quarré, S.; Simar, S.; Temmerman, P.D.; Verleysen, E; Mast, J.; Jensen, K.A.; Norppa, H.; Nesslany, F.; Silva, Maria JoãoToxicological characterization of manufactured nanomaterials (NMs) is essential for safety assessment, while keeping pace with innovation from their development and application in consumer products. The specific physicochemical properties of NMs, including size and morphology, might influence their toxicity and have impact on human health. The present work aimed to evaluate the genotoxicity of nanosized titanium dioxide (TiO2), synthetic amorphous silica (SAS) and multiwalled carbon nanotubes (MWCNT), in human lymphocytes. The morphology and size of those NMs were characterized by transmission electron microscopy, while the hydrodynamic particle size-distributions were determined by dynamic light scattering. Using a standardized procedure to ensure the dispersion of the NMs and the cytokinesis-block micronucleus assay (without metabolic activation), we observed significant increases in the frequencies of micronucleated binucleated cells (MNBC) for some TiO2 NMs and for two MWCNTs, although no clear dose–response relationships could be disclosed. In contrast, all forms of SAS analyzed in this study were unable to induce micronuclei. The present findings increase the weight of evidence towards a genotoxic effect of some forms of TiO2 and some MWCNT. Regarding safety assessment, the differential genotoxicity observed for closely related NMs highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NMs.
- HBM4EU Occupational Biomonitoring Study on e-Waste-Study ProtocolPublication . Scheepers, Paul T.J.; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Hardy, Emilie; Knudsen, Lisbeth E.; Leese, Elizabeth; Louro, Henriqueta; Mahiout, Selma; Ndaw, Sophie; Poels, Katrien; Porras, Simo P.; Silva, Maria João; Tavares, Ana Maria; Verdonck, Jelle; Viegas, Susana; Santonen, Tiina; HBM4EU e-Waste Study TeamWorkers involved in the processing of electronic waste (e-waste) are potentially exposed to toxic chemicals. If exposure occurs, this may result in uptake and potential adverse health effects. Thus, exposure surveillance is an important requirement for health risk management and prevention of occupational disease. Human biomonitoring by measurement of specific biomarkers in body fluids is considered as an effective method of exposure surveillance. The aim of this study is to investigate the internal exposure of workers processing e-waste using a human biomonitoring approach, which will stimulate improved work practices and contribute to raising awareness of potential hazards. This exploratory study in occupational exposures in e-waste processing is part of the European Human Biomonitoring Initiative (HBM4EU). Here we present a study protocol using a cross sectional survey design to study worker's exposures and compare these to the exposure of subjects preferably employed in the same company but with no known exposure to industrial recycling of e-waste. The present study protocol will be applied in six to eight European countries to ensure standardised data collection. The target population size is 300 exposed and 150 controls. Biomarkers of exposure for the following chemicals will be used: chromium, cadmium and lead in blood and urine; brominated flame retardants and polychlorobiphenyls in blood; mercury, organophosphate flame retardants and phthalates in urine, and chromium, cadmium, lead and mercury in hair. In addition, the following effect biomarkers will be studied: micronuclei, epigenetic, oxidative stress, inflammatory markers and telomere length in blood and metabolomics in urine. Occupational hygiene sampling methods (airborne and settled dust, silicon wristbands and handwipes) and contextual information will be collected to facilitate the interpretation of the biomarker results and discuss exposure mitigating interventions to further reduce exposures if needed. This study protocol can be adapted to future European-wide occupational studies.
- Occupational Exposure to Hexavalent Chromium, Nickel and PAHs: A Mixtures Risk Assessment Approach Based on Literature Exposure Data from European CountriesPublication . Tavares, Ana Maria; Viegas, Susana; Louro, Henriqueta; Göen, Thomas; Santonen, Tiina; Luijten, Mirjam; Kortenkamp, Andreas; Silva, Maria JoãoHexavalent chromium (Cr(VI)), nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs) are genotoxic co-occurring lung carcinogens whose occupational health risk is still understudied. This study, conducted within the European Human Biomonitoring Initiative (HBM4EU), aimed at performing a mixtures risk assessment (MRA) based on published human biomonitoring (HBM) data from Cr(VI), Ni and/or PAHs occupational co-exposure in Europe. After data extraction, Risk Quotient (RQ) and Sum of Risk Quotients (SRQ) were calculated for binary and ternary mixtures to characterise the risk. Most selected articles measured urinary levels of Cr and Ni and a SRQ > 1 was obtained for co-exposure levels in welding activities, showing that there is concern regarding co-exposure to these substances. Similarly, co-exposure to mixtures of Cr(VI), Ni and PAHs in waste incineration settings resulted in SRQ > 1. In some studies, a low risk was estimated based on the single substances’ exposure level (RQ < 1), but the mixture was considered of concern (SRQ > 1), highlighting the relevance of considering exposure to the mixture rather than to its single components. Overall, this study points out the need of using a MRA based on HBM data as a more realistic approach to assess and manage the risk at the workplace, in order to protect workers’ health.
- Occupational exposure to metals and PAHs: combining literature-based exposure and in vitro hazard data towards a mixture risk assessment a mixture risk assessmentPublication . Tavares, Ana Maria; Alves, Inês; Moreira, Rodrigo; Louro, Henriqueta; Ladeira, Carina; Viegas, Susana; Loureiro, Susana; Santonen, Tiina; Göen, Thomas; Kortenkamp, Andrew; Luijten, Mirjam; Silva, Maria JoãoThe environment within industrial settings is commonly characterized by the existence of a complex mixture of chemicals from different raw materials and transformation processes. Occupational co-exposure to chromium (Cr), Nickel (Ni), and Polycyclic Aromatic Hydrocarbons (PAHs) may occur in diverse workplaces, such as the aeronautic and waste management, (e.g incineration) sectors. Such co-exposure rais-es concern in terms of occupational health, as these substances are recognized lung carcinogens and mainly act by genotoxic mechanisms, increasing the likelihood of interactive toxic effects. The fact that cur-rent regulatory practices are usually focused on single chemical sub-stances, without integrating the possibility of combined or aggregated exposures and effects, may lead to a risk underestimation.In this work, developed under the scope of HBM4EU Initiative (https://www.hbm4eu.eu), a literature-based mixture risk assess-ment (MRA) exercise for occupational exposure to metals and PAHs was performed. In addition, in vitro toxicity data was obtained for the same mixtures to provide support to its hazard assessment.Human biomonitoring (HBM) data on Cr(VI), Ni and/or PAHs was extracted from occupational studies conducted in the European Un-ion and searched in literature databases. Selected reference values were used to calculate risk quotients (RQ) for each substance based on the retrieved exposure data; the combined risk was given by the sum of the RQ, i.e., the Background Exposure Exceedance Score(BEES).In parallel, we evaluated the combined cyto- and genotoxicity of the same chemicals (assessed by the MTT and micronucleus assays) in the human alveolar A549 cell line.In most of the analysed studies, we observed that BEES levels, estimated from the exposure to metals mixture or to metals and PAHs, exceeded RQ levels considered acceptable for the individual substances. Only two studies, conducted in hazard waste incinerator settings, presented urinary exposure levels for the three substances. They showed a value of BEES of concern (>1) for all exposure sce-narios, even for workers performing activities considered of low ex-posure or no-exposure, such as laboratory and administrative work-ers. In vitro assays supported that A549 cells exposure to these substances resulted in interactive cytotoxic and genotoxic effects that may underlie health effects different from those predicted from single exposures.Our findings show the limitations of applying occupational expo-sure reference values defined on a single substance basis to work-places where exposure to chemical mixtures occur, highlighting the relevance of performing MRA as a more realistic approach to guide suitable risk management measures in occupational settings
- O projeto HBM4EU - exemplo de biomonitorização da exposição ocupacional ao crómioPublication . Tavares, Ana Maria; Louro, Henriqueta; Silva, Maria JoãoAula 5: O projeto HBM4EU - exemplo de biomonitorização da exposição ocupacional ao crómio. Projeto HBM4EU - General objective: To understand human exposure to chemicals and resulting health impacts and communicate with policy makers to ensure that the results are exploited in the design of new chemicals policies and the evaluation of existing measures.
- Risk assessment of combined occupational exposure to hexavalent chromium, nickel, and PAHs: a literature-based approachPublication . Tavares, Ana Maria; Viegas, Susana; Louro, Henriqueta; Silva, Maria JoãoOccupational exposure is usually characterized by a complex mixture of chemicals, originating from different raw materials and transformation processes. Co-exposure to hexavalent chromium (Cr(VI)), nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs) can occur in some workplaces. These substances display well-known genotoxic and carcinogenic effects, especially in the respiratory tract, sharing similar modes of action. However, reference values for occupational exposure only account for individual components exposure and not for a potential mixture effect. In the scope of HBM4EU Initiative, we performed a mixtures risk assessment (MRA) based on literature from occupational studies conducted in the European Union that contain human biomonitoring (HBM) data on Cr(VI), Ni and/or PAHs. After HBM data extraction, Hazard Quotient (HQ) and Hazard Index (HI) were calculated for binary and tertiary mixtures. Exposure was considered of concern if HI>1. Twenty-four articles were selected, most (n=18, 75%) presenting Cr(VI) and Ni exposure biomarkers. Among these, HI>1 was obtained for all studies on welding activities, in which chromium was the main driver of toxicity with HQ>1 in most measurements. Only two studies in waste incineration setting reported exposure to the three substances, and again all HI>1. Noteworthy, for some of the analysed studies, although exposure levels were below the reference values, still the mixture was considered of concern (HI>1). Our findings show the limitations of applying occupational exposure reference values defined on a single substance basis to workplaces, highlighting the relevance of MRA as a more realistic approach to provide more suitable risk management measures in occupational settings.