Browsing by Issue Date, starting with "2019-08-29"
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- 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.
- Evaluation of the cytotoxicity and genotoxicity of ingested titanium dioxide nanomaterials in intestinal cellsPublication . Gramacho, Ana Catarina; Martins, Carla; Assunção, Ricardo; Gonçalves, Lídia; Simão Bettencourt, Ana; Paula, Alvito; Silva, Maria João; Louro, HenriquetaMany products already available, namely in agriculture and food, contain nanomaterials (NMs) and thus human ingestion of these compounds is probable through consumer products or food chain. Although NMs have been extensively investigated in recent years, the studies have generated contradictory results, possibly due to differences in the physicochemical properties of the NMs studied and to other variables in the tested systems. Furthermore, the NMs properties have been recognized as being context-dependent, i.e. can be affected by the surrounding matrix. These secondary features may be potentially more relevant for determining the toxicological outcome. In particular, processes like digestion may modify the NMs characteristics leading to unexpected toxicity in intestine cells. This work aimed to investigate the nano-bio interactions of titanium dioxide NMs (from Joint Research Centre, Ispra) in the context of intestinal tract and digestion processes, to better understand key events that may be linked to an adverse outcome pathway (AOP). In vitro for digestion was simulated and the NMs secondary properties in the intestinal cell moiety were characterized after this process. The cytotoxic and genotoxic effects of digested NMs were determined after the in vitro exposure of human intestinal cells (Caco-2). In addition, the FPG-comet assay was used to analyze oxidative DNA lesions. The digestion products without the NM showed cytotoxic effects above the concentration of 10% in cell culture medium, leading to the need to reduce its concentration below this level. Therefore, initial dose-range studies set a working range of NM concentrations of 0.14 up to 14 µg/ml (0.5-4.5 % of digestion product), which relates also with the predicted levels of exposure of human intestinal cells in real life conditions. Under these conditions, the preliminary results suggest that the tested titanium dioxide NMs do not yield cytotoxic or genotoxic effects upon 24h of exposure of Caco-2 cells, directly after the digestion process. Future studies will investigate the subcellular localization of NMs, integrity of cell junctions, activation of stress signaling pathways and secretion of inflammatory cytokines, to allow an integrated approach to potential adverse effects of the NMs. By elucidating key events elicited by NMs, linking exposure to adverse outcomes, it is expected to contribute to the safety evaluation of NMs within an AOP landscape.
- Setting up a collaborative European Human biological monitoring study on occupational exposure to Hexavalent ChromiumPublication . Santonen, Tiina; Alimonti, Alessandro; Bocca, Beatrice; Duca, Radu Corneliu; Galea, Karen S.; Godderis, Lode; Göen, Thomas; Gomes, Bruno; Hanser, Ogier; Iavicoli, Ivo; Janasik, Beata; Jones, Kate; Kiilunen, Mirja; Koch, Holger M.; Leese, Liz; Leso, Veruscka; Louro, Henriqueta; Ndaw, Sophie; Porras, Simo P.; Robert, Alain; Ruggieri, Flavia; Scheepers, Paul; Silva, Maria João; Viegas, Susana; Wasowicz, Wojciech; Castano, Argelia; Sepai, OvnairBackground: The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring across Europe and develop new approaches for biomonitoring. Hexavalent chromium (Cr(VI)) is an important occupational carcinogen, which compounds are currently authorized in Europe. In addition, a binding limit value for occupational exposure to Cr(VI) has been recently agreed in EU. These regulatory actions emphasize the need for EU-wide data on exposure and sensitive biomarkers to assess the exposure. Here we describe the design of the multinational, collaborative project to support management of occupational exposure to Cr(VI). Methods: The study involves eight European countries and aims to recruit 400 workers performing Cr(VI) surface treatment or stainless steel welding. In addition to urinary chromium (U-Cr), exhaled breath condensate (EBC) and blood samples are collected for the analysis of Cr(VI)/Cr. Exposure data will be complemented with data on effect markers. Personal air and wipe samples are collected in parallel to help interpretation of biomonitoring results. Standardized questionnaires are used to collect contextual data, and samplings are done following the standard operational procedures developed to support standardization. Results: This occupational Cr(VI) study is the first that will be performed concurrently in multiple European countries using harmonized protocols for data gathering, sampling and analysis. Combining national standardized surveys the power of the study and the strength of the findings is greatly enhanced. Samplings are currently on-going and include companies ranging from micro-sized companies to large international companies. Final results are expected by the end of 2020. The presentation covers the background data on the tasks covered and the available external exposure data. Conclusions: Using this unique set-up including multiple countries and harmonized protocols we expect to create more comprehensive data for EU decision making. The data allows also the assessment of the feasibility of different biomarkers in the biomonitoring of Cr(VI).
- A case study on occupational exposure to Chromium (VI), Nickel, PAH mixtures and lung cancer.Publication . Silva, Maria João; Louro, Henriqueta; Viegas, Susana; Gomes, Bruno Costa; Santonen, Tiina; Kortenkamp, Andreas; Lebret, ErikBackground: In several industries, e.g., aircrafts maintenance, workers are co-exposed to a range of hazardous substances, including hexavalent chromium [Cr (VI)], nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs). Each of these compounds can cause serious health effects, including lung cancer. However, the association between exposure and health outcome has not been analysed from a mixture perspective, i.e., considering the potential interactive effects of those substances as determinants of lung cancer. Here we present the development of a case study on occupational exposure to Cr (VI), Ni and PAHs to advance the identification of mixture health effects and to progress towards a more refined risk assessment. Methods: A tiered framework is applied that includes a first step of collection of relevant hazard (e.g., genotoxicity) and exposure information gathered from literature or from HBM4EU databases on occupational cohorts. Then, this information will be used to construct hazard quotients derived from relevant occupational exposure limits for Cr (VI), Ni and PAHs, followed by the determination of the Hazard Index (HI). Results: The estimations based on available literature search will be presented and discussed, keeping the perspective of its contribution to generate directions for the exposure, hazard, and risk assessments. In addition, the biomonitoring levels of Cr (VI) and Ni and the data on external levels of PAHs produced in the chromate occupational exposure study, will allow a refinement of the exposure assessment, comparatively to the literature-based results obtained. Conclusions: It is anticipated that the assessment of the risk from occupational co-exposure to Cr(VI), Ni and PAHs - based on data obtained from a EU-wide harmonised study - will add on building a framework for mixtures risk assessment, that can be further applied for substances to which co-exposure occurs or/and are expected to produce similar health outcomes.
- Exploring the potential of microRNAs as biomarkers of effect of nanofibres using MWCNT-7-exposed alveolar cellsPublication . Ventura, Célia; Vieira, Luís; Silva, Catarina; Sousa-Uva, Antonio; Silva, Maria JoãoBackground: In the last years, several diseases have been associated with alterations in microRNA (miRNA) expression, and miRNA profiling has proved to be useful to detect or evaluate disease progression. Moreover, there has been attempts to identify differentially expressed (DE) miRNA after exposure to toxicants that could be used as biomarkers of effect. Since human exposure to nanofibres, such as the MWCNT-7, has considerably increased due to their incorporation in several consumer products, this work explores the use of DE miRNA for monitoring human exposure to MWCNT-7 and their effects. Methods: We analyzed DE miRNAs in A549 alveolar cells following 24 hours exposure to an occupationally relevant dose of MWCNT-7. Total RNA was used to generate cDNA libraries for sequencing in MiSeq (Illumina). Differential expression analysis of miRNAs between non-exposed and exposed cells was performed using DESeq2 and EdgeR Exact Test. Results: Several under- and over-expressed miRNAs were sequenced in A549 cells after 24 h exposure to MWCNT-7. After filtering them according to the criteria adopted, a set of 17 DE miRNAs was identified. Some of these miRNAs have been reported as regulators of pathways related to cell growth, proliferation, differentiation and survival. Conclusions: Although more studies are needed, it is likely that the miRNA profile here identified may provide a novel biomarker of human exposure to MWCNT-7 by inhalation.