Loading...
8 results
Search Results
Now showing 1 - 8 of 8
- 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.
- The use of effect biomarkers in human biomonitoring studies: exposure to hexavalent chromiumPublication . Gomes, Bruno Costa; Louro, Henriqueta; Huuskonen, Pasi; Santonen, Tiina; Huumonen, Katriina; Ndaw, Sophie; Fernández, Mariana F.; Silva, Maria JoãoHexavalent chromium, Cr(VI) is a human carcinogen (Group 1, IARC), and its expo-sure has been associated with increased lung cancer risk, particularly in exposed workers. The general population may be exposed to Cr(VI) through food, drinking water and tobacco smoke. Under the Human Biomonitoring for Europe Initiative (HBM4EU), Cr(VI) has been considered a priority substance, indicating the need for generating and analyzing data on human exposure and effects, both as single sub-stance and in mixtures. Although many epidemiological studies have reported data on human exposure to Cr(VI), comparably fewer included effect biomarkers assess-ment. However, these biomarkers are central to identify early biological effects be-fore the onset of any adverse health effect. Additionally, biomarkers provide a link between human exposure and health outcomes, when considered in an adverse outcome pathway (AOP) perspective. In this work, we present the results of a critical review on the conventional and po-tentially new biomarkers for Cr(VI) early biological effects, which may be linked to adverse health outcomes in humans. The results show that the most frequently analyzed effect biomarkers concerning Cr(VI) exposure have been those associated with oxidative stress and genotoxicity (comet and micronucleus in blood cells). Urinary 8-isoprostane, a marker of lipid pe-roxidation, has also been used to relate Cr(VI) exposure to lung cancer. More recent-ly, single-gene alterations as well as omics-based biomarkers e.g., genomic or epigenomic changes and protein signatures, have been pointed as novel effect bi-omarkers, but they still need to be further developed and validated. In the literature revision, the most important knowledge gaps have also been identi-fied and discussed, such as the need of additional mechanistic data, in the perspec-tive of building an AOP for Cr(VI) occupational exposure and lung cancer
- 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.
- Aula 6: microRNAs association with drug resitancePublication . Gomes, Bruno; Silva, Maria JoãomiRNAs are short (approximately 22 nucleotides) non-coding RNAs with gene regulatory effect
- 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.
- Occupational exposure to hexavalent chromium: biomarkers of genotoxicity in human peripheral bloodPublication . Afonso, Catarina; Gomes, Bruno Costa; Louro, Henriqueta; Nogueira, Ana; Pinhal, Hermínia; Reis, Susana; Ventura, Célia; Ladeira, Carina; Ribeiro, Edna; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoThe hexavalent chromium [Cr(VI)] is a human carcinogen, which is still authorized for use in several industrial settings because it has been difficult to replace. This was the reasoning to select it as a priority chemical by the European Human Biomonitoring Initiative (HBM4EU, https://www.hbm4eu.eu/), which aims to bridge chemicals human exposure to their possible impact on health. For that purpose, not only exposure needs to be assessed but also early effect biomarkers are valuable to reflect health outcomes. The cytokinesis-block micronucleus (CBMN) assay in peripheral blood lymphocytes (PBLs) is one of the most widely used effect biomarker for measuring chromosome alterations in human cells. Since it represents a measure of both chromosome breakage and loss, an increased frequency of micronucleated cells (MNC) can reflect the effect from exposure to genotoxic agents. Moreover, there is evidence that the micronucleus (MN) frequency in PBLs is predictive of cancer risk. As part of an European multi-centre occupational study, 50 Portuguese workers exposed on a daily basis to Cr(VI) and 27 healthy controls non-exposed to Cr(VI) or other chemicals were studied. The present work intended to assess, in a more detailed manner, the early effects in a subgroup of workers (n=6) that use daily paints with Cr(VI), comparatively to that of a control group matched for age, gender and smoking habits. All participants accepted to participate by signing an informed consent previously to the blood withdrawal. An individual questionnaire to collect contextual information, e.g. personal information, lifestyle habits (smoking habits, alcohol consumption, diet), and health status was filled. Personal air samples were collected in order to assess occupational exposure to Cr(VI) soluble and insoluble compounds. Following blood culture, lymphocytes harvesting and staining using standardized methods, MNC were scored in 2000 PBL per individual. The frequencies of MNC obtained for the exposed and control groups were compared using Fisher’s exact test. Results from personal air sampling are still under evaluation. A significantly increased frequency of MNC was observed in PBLs of the 6 workers under study, comparatively to the matched controls (p < 0.001, Fisher’s exact test). These results are in line with the preliminary data obtained for the overall exposed group vs controls. The present results suggest that the frequency of micronuclei in PBLs is a reliable early effect biomarker in the case of occupational exposure to Cr(VI). Moreover, the findings also suggest a potential health risk for this group of workers. These results should promote the investment in new risk management measures and the effective application of the ones already in place, such as adequate local exhaust ventilation and a more frequent use of personal protective equipment. Additional work, considering the overall exposed group, will be developed aiming to clarify if the obtained results are due to the single exposure to Cr(VI) or to the co-exposure to several other chemicals commonly present in this type of occupational setting.
- Using human biomonitoring for the risk assessment of polycyclic aromatic hydrocarbons in occupational exposuresPublication . Viegas, Susana; Gomes, Bruno Costa; Louro, Henriqueta; Silva, Maria João; Joksić, Agnes Šömen; Kirinčič, Stanislava; Mahiout, Selma; Santonen, TiinaBackground and Purpose: The Human Biomonitoring Initiative (HBM4EU) is a joint effort of 28 countries, the European Environment Agency and the European Commission, co-funded under Horizon 2020. HBM4EU is generating evidence of the current exposure of European citizens to chemicals and the possible health effects in order to assess the associated risks and support policy making towards human health protection. Polycyclic aromatic hydrocarbons (PAH) were considered one of the 1st priority substance groups to be addressed. In the scope of this project, the present work aimed to evaluate the added value of human biomonitoring (HBM) for the PAH risk assessment process, in the case of occupational exposure. Methods: An extensive literature search was performed to identify scientific papers published between 2008 and 2018 that included air monitoring and HBM data in several occupational settings based in Europe. Among them, those papers presenting urinary 1-hydroxypyrene (1-OHP) quantification - the most common exposure biomarker of pyrene and a surrogate for exposure to PAHs mixtures - were selected. Based on the 1-OHP values the excess lifetime cancer risk (ELCR) for workers, concerning lung cancer, was estimated following the ECHA recent approach (https://echa.europa.eu/fi/applying-for-authorisation/evaluating-applications). ELCR values calculated using air and HBM data were compared. Results: Based on the criteria described, only 7 out of 28 papers were considered for ELCR estimation. Overall, high ELCR values were estimated (several values higher than 10-4). Moreover, for some studies (3 out of 7) the ELCR estimation using HBM data yielded values higher than those estimated from air monitoring data. This might indicate that, for those specific workplaces, transdermal absorption or even hand-mouth exposure can have an important role in the total exposure to PAH and that the HBM data allows a more accurate PAH exposure assessment. Nevertheless, these findings should be interpreted with caution, since ELCR estimates from air monitoring data are based on Benzo[a]pyrene (BaP) concentrations while HBM-based ELCR determination uses urinary 1-OHP concentration that reflects exposure not only to BaP but to all PAHs, irrespectively of sources or routes of exposure. This work claims attention for two main aspects, namely: i) the exposure levels are still high in some occupational settings and ii) there is a need for developing new occupational studies, applying a set of exposure biomarkers or a more specific biomarker for BaP exposure, which would allow a better ELCR estimation for exposed workers.
- The relevance of effect biomarkers in human biomonitoringPublication . Gomes, Bruno; Louro, Henriqueta; Silva, Maria JoãoA fundamental goal of environmental/occupational health policy is to reduce and, whenever possible, prevent human exposure to chemical substances that may lead to morbidity or mortality. Human biomonitoring (HBM) allows the assessment of the levels of certain substances in the body, through the analysis of biomarkers of exposure (chemical substances, metabolites) and it has been considered as an extremely important tool in public health. A great strength of HBM is that it provides unambiguous indication that both exposure and absorption have occurred. On the other hand, measuring uniquely exposure biomarkers does not provide information on preclinical effects that may allow establishing a link between exposure and health effects. This work aims summarizing the most used biomarkers of effect and give evidence of the importance of these biomarkers in HBM and public health protection, based on recently published data. Briefly, these biomarkers consist of biochemical alterations in urine or blood, endocrine changes, cytogenetic alterations [micronuclei, chromosomal aberrations, translocations, sister chromatid exchanges and DNA repair] or interactions with macromolecules such as DNA, RNA and proteins through the recent –omics technologies. The inclusion of biomarkers of effect in HBM studies contributes to bridge the gap between exposure and health effects, because they give information on early biological alterations before the onset of disease. Given that these biomarkers reflect reversible alterations in the organism, the effects detected are likely to be prevented, if exposure to the critical substance (or mixture of substances) is reduced or ceased. Thus, the joint information gathered from biomarkers of exposure and effect in HBM can be used to improve health risk assessment and reinforce the scientific basis to implement preventive policies in occupational and environmental settings. The HBM4EU project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032.