Browsing by Author "Ladeira, Carina"
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- Biomonitorização da exposição profissional ao crómio hexavalente: contributo para proposta de valores-limite biológicosPublication . Pinhal, Hermínia; Nogueira, Ana; Santos, Sílvia; Ribeiro, Edna; Ladeira, Carina; Viegas, SusanaO crómio hexavalente (Cr ( VI ) ) é um agente cancerígeno para o ser humano, estando na origem de cancro no pulmão. As indústrias em que ocorre exposição ao Cr ( VI ) incluem a produção, utilização e soldadura de metais e ligas contendo crómio. O presente estudo tem como objetivo analisar os resultados de monitorização ambiental e biológica da exposição profissional ao Cr ( VI ) no âmbito da participação portuguesa na Iniciativa Europeia de Biomonitorização Humana (HBM4EU ). O estudo envolveu 50 trabalhadores expostos a Cr ( VI ) e 27 controlos. Realizou-se monitorização ambiental, por amostragem pessoal do ar, para estudar a exposição a Cr ( VI ) e monitorização biológica ( urina e eritrócitos ). Os resultados obtidos neste estudo sugerem que os pintores são o grupo com maior exposição externa e interna ao Cr ( VI ). Os trabalhadores dos banhos eletrolíticos apresentam uma exposição relevante, quando comparada com o valor limite de exposição de 0,005 mg/m3 apesar de consideravelmente inferior à dos pintores. Os resultados das medições de Cr-U pós-turno, quando agregados ao nível do grupo profissional apresentaram boa correlação ( ρ=0,63 ) com a fração respirável de Cr ( VI ) no ar, apoiando a utilização do Cr-U para a biomonitorização da exposição ao Cr ( VI ) nos locais de trabalho. A diferente cinética dos indicadores biológicos estudados pode ser a razão pela qual não se verificou uma boa correlação entre Cr-U pós-turno e Cr-RBC ( ρ<0,5 ), no entanto podem fornecer informação complementar relevante para a prevenção.
- Caracterização de biomarcadores de genotoxicidade em trabalhadores expostos a crómio hexavalente: um estudo no âmbito da Iniciativa Europeia em Biomonitorização HumanaPublication . Tavares, Ana; Aimonen, Kukka; Ndaw, Sophie; Fučić, Aleksandra; Catalán, Julia; Duca, Radu Corneliu; Godderis, Lode; Gomes, Bruno C.; Janasik, Beata; Ladeira, Carina; Louro, Henriqueta; Namorado, Sónia; Van Nieuwenhuyse, An; Norppa, Hannu; Scheepers, Paul T.J.; Ventura, Célia; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Santonen, Tiina; Silva, Maria JoãoNo âmbito da Iniciativa Europeia em Biomonitorização Humana (HBM4EU) realizou-se um estudo ocupacional, envolvendo trabalhadores com potencial exposição a crómio hexavalente [Cr( VI)], um reconhecido agente carcinogénico. No presente estudo são apresentados os resultados de biomarcadores de genotoxicidade, incluindo a análise de lesão no DNA e de alterações cromossómicas em células sanguíneas. O estudo foi realizado em vários Países Europeus e abrangeu trabalhadores de diversos setores industriais e atividades, bem como um grupo de controlo constituído por trabalhadores administrativos das mesmas empresas (controlo interno) e de outras não relacionadas com produção/aplicação de Cr( VI) (controlo externo). Os resultados mostraram níveis de alterações cromossómicas (ensaio do micronúcleo) e de lesão no DNA (ensaio do cometa) significativamente aumentados nos trabalhadores expostos comparativamente aos controlos externos ( p=0,03; p<0,001, respetivamente). Estes resultados sugerem que mesmo um baixo nível de exposição ao Cr( VI) representa um risco acrescido para a saúde dos trabalhadores e, principalmente, para os que realizam cromagem em banho. O grupo controlo interno apresentou níveis médios de lesões no DNA e nos cromossomas comparáveis aos do grupo exposto, salientando a relevância de se considerarem também em risco. O uso de biomarcadores de efeito demonstrou ser crucial para a deteção precoce de efeitos biológicos decorrentes de baixos níveis de exposição ao Cr( VI), contribuindo para a identificação de subgrupos em maior risco. O presente estudo vem apoiar a necessidade de uma reavaliação do limite de exposição ocupacional a Cr( VI), bem como da implementação de medidas de gestão de risco conducentes a uma melhor proteção da saúde dos trabalhadores.
- DNA damage in circulating leukocytes measured with the comet assay may predict the risk of deathPublication . Bonassi, Stefano; Ceppi, Marcello; Møller, Peter; Azqueta, Amaya; Milić, Mirta; Neri, Monica; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine A.S.; Teixeira, João Paulo; Bruzzone, Marco; Da Silva, Juliana; Benedetti, Danieli; Cavallo, Delia; Ursini, Cinzia Lucia; Giovannelli, Lisa; Moretti, Silvia; Riso, Patrizia; Del Bo’, Cristian; Russo, Patrizia; Dobrzyńska, Malgorzata; Goroshinskaya, Irina A.; Surikova, Ekaterina I.; Staruchova, Marta; Barančokova, Magdalena; Volkovova, Katarina; Kažimirova, Alena; Smolkova, Bozena; Laffon, Blanca; Valdiglesias, Vanessa; Pastor, Susana; Marcos, Ricard; Hernández, Alba; Gajski, Goran; Spremo-Potparević, Biljana; Živković, Lada; Boutet-Robinet, Elisa; Perdry, Hervé; Lebailly, Pierre; Perez, Carlos L.; Basaran, Nursen; Nemeth, Zsuzsanna; Safar, Anna; Dusinska, Maria; Collins, Andrew; Anderson, Diana; Andrade, Vanessa; Pereira, Cristiana Costa; Costa, Solange; Gutzkow, Kristine B.; Ladeira, Carina; Moretti, Massimo; Costa, Carla; Orlow, Irene; Rojas, Emilio; Pourrut, Bertrand; Kruszewski, Marcin; Knasmueller, Siegfried; Shaposhnikov, Sergey; Žegura, Bojana; Stopper, HelgaThe comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.
- Exposição a substâncias químicas na indústria da gestão de resíduos elétricos e eletrónicos e seus potenciais efeitos na saúde dos trabalhadoresPublication . Moreira, Rodrigo; Tavares, Ana M.; Louro, Henriqueta; Ventura, Célia; Ladeira, Carina; Viegas, Susana; Silva, Maria JoãoOs resíduos de equipamento elétrico e eletrónico (REEE) são um problema crescente a nível global, sendo considerados um perigo para a saúde humana e ambiental devido à presença de uma variedade de substâncias nocivas, tais como poluentes orgânicos persistentes e metais pesados. Os trabalhadores envolvidos na gestão deste tipo de resíduos estão potencialmente expostos a estas substâncias, particularmente, durante as atividades de reciclagem e processamento. Esta revisão teve por objetivo recolher informação referente à exposição ocupacional a substâncias químicas no sector da gestão de REEE e aos seus potenciais efeitos na saúde dos trabalhadores. A consulta a duas bases de dados (PubMed e Scopus) seguida da aplicação dos critérios de inclusão e exclusão resultou na seleção de 14 estudos que foram sujeitos a uma análise mais detalhada. Os referidos estudos de biomonitorização ocupacional reportaram a exposição dos trabalhadores deste setor a vários metais pesados e compostos orgânicos. A análise de biomarcadores de efeito biológico precoce sugeriu, na maioria dos estudos, uma associação entre a exposição a este tipo de resíduos e alterações hormonais ou genotoxicidade em células sanguíneas. Os referidos efeitos, a confirmarem-se em estudos futuros, poderão traduzir-se a longo termo em patologias, tais como desregulação endócrina ou neoplasias. Em conclusão, embora os estudos revistos sugiram que trabalhar no sector de gestão de REEE representa um potencial risco para os trabalhadores, torna-se necessária a realização de mais estudos de biomonitorização humana, especialmente ao nível europeu, para gerar evidência sólida que apoie medidas de mitigação da exposição desses trabalhadores.
- HBM4EU Chromates Study - Genotoxicity and Oxidative Stress Biomarkers in Workers Exposed to Hexavalent ChromiumPublication . Tavares, Ana; Aimonen, Kukka; Ndaw, Sophie; Fučić, Aleksandra; Catalán, Julia; Duca, Radu Corneliu; Godderis, Lode; Gomes, Bruno C.; Janasik, Beata; Ladeira, Carina; Louro, Henriqueta; Namorado, Sónia; Nieuwenhuyse, An Van; Norppa, Hannu; Scheepers, Paul; Ventura, Célia; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Santonen, Tiina; Silva, M.J.; on behalf of the HBM4EU Chromates Study TeamA study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and malondialdehyde and 8-oxo-2'-deoxyguanosine in urine. Workers from several Cr(VI)-related industrial activities and controls from industrial (within company) and non-industrial (outwith company) environments were included. The significantly increased genotoxicity (p = 0.03 for MN in lymphocytes and reticulocytes; p < 0.001 for comet assay data) and oxidative stress levels (p = 0.007 and p < 0.001 for MDA and 8-OHdG levels in pre-shift urine samples, respectively) that were detected in the exposed workers over the outwith company controls suggest that Cr(VI) exposure might still represent a health risk, particularly, for chrome painters and electrolytic bath platers, despite the low Cr exposure. The within-company controls displayed DNA and chromosomal damage levels that were comparable to those of the exposed group, highlighting the relevance of considering all industry workers as potentially exposed. The use of effect biomarkers proved their capacity to detect the early biological effects from low Cr(VI) exposure, and to contribute to identifying subgroups that are at higher risk. Overall, this study reinforces the need for further re-evaluation of the occupational exposure limit and better application of protection measures. However, it also raised some additional questions and unexplained inconsistencies that need follow-up studies to be clarified.
- HBM4EU chromates study - Overall results and recommendations for the biomonitoring of occupational exposure to hexavalent chromiumPublication . Santonen, Tiina; Porras, Simo P.; Bocca, Beatrice; Bousoumah, Radia; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Göen, Thomas; Hardy, Emilie; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Leese, Elizabeth; Leso, Veruscka; Louro, Henriqueta; Majery, Nicole; Ndaw, Sophie; Pinhal, Hermínia; Ruggieri, Flavia; Silva, Maria João; van Nieuwenhuyse, An; Verdonck, Jelle; Viegas, Susana; Wasowicz, Wojciech; Sepai, Ovnair; Scheepers, Paul T.J.; Aimonen, Kukka; Antoine, Guillaume; Anzion, Rob; Burgart, Manuella; Castaño, Argelia; Cattaneo, Andrea; Cavallo, Domenico Maria; De Palma, Giuseppe; Denis, Flavien; Gambelunghe, Angela; Gomes, Bruno; Hanser, Ogier; Helenius, Riikka; Ladeira, Carina; López, Marta Esteban; Lovreglio, Piero; Marsan, Philippe; Melczer, Mathieu; Nogueira, Ana; Pletea, Elisabeta; Poels, Katrien; Remes, Jouko; Ribeiro, Edna; Santos, Sílvia Reis; Schaefers, Françoise; Spankie, Sally; Spoek, Robert; Rizki, Mohamed; Rousset, Davy; van Dael, Maurice; Veijalainen, Henna; HBM4EU chromates study teamExposure to hexavalent chromium [Cr(VI)] may occur in several occupational activities, e.g., welding, Cr(VI) electroplating and other surface treatment processes. The aim of this study was to provide EU relevant data on occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making. In addition, the capability and validity of different biomarkers for the assessment of Cr(VI) exposure were evaluated. The study involved nine European countries and involved 399 workers in different industry sectors with exposures to Cr(VI) such as welding, bath plating, applying or removing paint and other tasks. We also studied 203 controls to establish a background in workers with no direct exposure to Cr(VI). We applied a cross-sectional study design and used chromium in urine as the primary biomonitoring method for Cr(VI) exposure. Additionally, we studied the use of red blood cells (RBC) and exhaled breath condensate (EBC) for biomonitoring of exposure to Cr(VI). Personal measurements were used to study exposure to inhalable and respirable Cr(VI) by personal air sampling. Dermal exposure was studied by taking hand wipe samples. The highest internal exposures were observed in the use of Cr(VI) in electrolytic bath plating. In stainless steel welding the internal Cr exposure was clearly lower when compared to plating activities. We observed a high correlation between chromium urinary levels and air Cr(VI) or dermal total Cr exposure. Urinary chromium showed its value as a first approach for the assessment of total, internal exposure. Correlations between urinary chromium and Cr(VI) in EBC and Cr in RBC were low, probably due to differences in kinetics and indicating that these biomonitoring approaches may not be interchangeable but rather complementary. This study showed that occupational biomonitoring studies can be conducted successfully by multi-national collaboration and provide relevant information to support policy actions aiming to reduce occupational exposure to chemicals.
- 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.
- In vitro combined toxicity of chromium, nickel and PAHS in human lung cells as support for mixtures risk assessmentPublication . Alves, Inês; Ladeira, Carina; Tavares, Ana M.; Viegas, Susana; Louro, Henriqueta; Silva, Maria JoãoRisk assessment of chemicals mainly relies on exposure to single chemicals and their hazardous effects, although the real scenario in occupational settings is more commonly characterized by exposure to chemi-cal mixtures. Chromium (Cr), Nickel (Ni), and Polycyclic Aromatic Hydrocarbons (PAHs) are often pre-sent in occupational settings, such as aeronautic industries, where workers are exposed primarily through inhalation. Considering that those substances are recognized lung carcinogens acting mainly by genotoxic mechanisms, it is likely that interactive effects occur, indicating that the risk from occupational exposure to these chemicals should be assessed as a mixture. Such issue is being addressed in the HBM4EU Initiati-ve, where a real scenario of occupational exposure has been studied. In order to provide support to the hazard assessment of the referred mixture, the present work aimed to evaluate the combined toxicity of Cr(VI), Ni, and benzo(a)pyrene (BaP), using a human lung cell line (A549 cells). MTT assay was performed for each individual chemical and a dose-response curve was esta-blished, enabling the determination of the IC50. The combined toxicity of the Cr and Ni mixture as well as that of Cr, Ni and BaP were determined comparatively to the single chemicals’ toxicity to ascertain whet-her additive effects or deviations from additivity towards synergism or antagonism was obtained. The results will be presented and discussed and are expected to contribute to the overall mixture’s risk asses-sment.
- Measuring DNA modifications with the comet assay: a compendium of protocolsPublication . Collins, Andrew; Møller, Peter; Gajski, Goran; Vodenková, Soňa; Abdulwahed, Abdulhadi; Anderson, Diana; Bankoglu, Ezgi Eyluel; Bonassi, Stefano; Boutet-Robinet, Elisa; Brunborg, Gunnar; Chao, Christy; Cooke, Marcus S.; Costa, Carla; Costa, Solange; Dhawan, Alok; de Lapuente, Joaquin; Bo’, Cristian Del; Dubus, Julien; Dusinska, Maria; Duthie, Susan J.; Yamani, Naouale El; Engelward, Bevin; Gaivão, Isabel; Giovannelli, Lisa; Godschalk, Roger; Guilherme, Sofia; Gutzkow, Kristine B.; Habas, Khaled; Hernández, Alba; Herrero, Oscar; Isidori, Marina; Jha, Awadhesh N.; Knasmüller, Siegfried; Kooter, Ingeborg M.; Koppen, Gudrun; Kruszewski, Marcin; Ladeira, Carina; Laffon, Blanca; Larramendy, Marcelo; Hégarat, Ludovic Le; Lewies, Angélique; Lewinska, Anna; Liwszyc, Guillermo E.; de Cerain, Adela López; Manjanatha, Mugimane; Marcos, Ricard; Milić, Mirta; de Andrade, Vanessa Moraes; Moretti, Massimo; Muruzabal, Damian; Novak, Matjaž; Oliveira, Rui; Olsen, Ann-Karin; Owiti, Norah; Pacheco, Mário; Pandey, Alok K.; Pfuhler, Stefan; Pourrut, Bertrand; Reisinger, Kerstin; Rojas, Emilio; Rundén-Pran, Elise; Sanz-Serrano, Julen; Shaposhnikov, Sergey; Sipinen, Ville; Smeets, Karen; Stopper, Helga; Teixeira, João Paulo; Valdiglesias, Vanessa; Valverde, Mahara; van Acker, Frederique; van Schooten, Frederik-Jan; Vasquez, Marie; Wentzel, Johannes F.; Wnuk, Maciej; Wouters, Annelies; Žegura, Bojana; Zikmund, Tomas; Langie, Sabine A.S.; Azqueta, AmayaThe comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA-DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility.
- Occupational exposure to Hexavalent chromium: the portuguese case within the collaborative european human biological monitoring studyPublication . Afonso, Catarina; Gomes, Bruno Costa; Louro, Henriqueta; Ladeira, Carina; Pinhal, Hermínia; Nogueira, Ana; Santos, Sílvia; Ventura, Célia; Ribeiro, Edna; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoBackground: The EU human biomonitoring initiative (HBM4EU) aims to coordinate and advance human biomonitoring across Europe. A multicenter study intending to characterize occupational exposure to hexavalent chromium [Cr(VI)], a human carcinogen, was setup in several industrial settings across Europe. In Portugal, the study was developed in one aircraft maintenance company since the substitution of Cr(VI) in this sector is not expected in the near future. Methods: The work processes that could imply exposure to Cr(VI) were characterized and exposure estimation was done. Following the company agreement and the volunteers informed consent, a survey was applied to each worker for detailed information on lifestyle, health status, etc.. Sampling for exposure and effect biomarkers analyses involved industrial hygiene samples (HIS) and biological specimens from 50 workers and 25 non-exposed individuals (controls). Biomarkers of early biological effects were studied in leukocytes from all individuals, involving the analysis of DNA damage (comet assay) and chromosome alterations (micronucleus assays); the results obtained for exposed and control individuals were statistically compared. Results and Discussion: Besides HIS results, Cr (VI) concentrations in biological samples and effect biomarkers results will be presented. The complementarity of the environmental and biological sampling, together with the sensitivity and specificity of the biomarkers used, is expected to allow exposure characterization and possible early genotoxic effects identification. Potential associations between exposure and effect biomarkers will be explored. Conclusions: An association between the levels of exposure to Cr(VI) and the early effects characterized in workers, if existent, is expected to predict potential health outcomes for Cr(VI)-exposed workers, particularly, on the long-term. All the information generated will help to support new priorities and investments regarding risk management measures to apply in this company and in the aircraft maintenance sector, in general.
