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- Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human healthPublication . Behr, Anne-Cathrin; Fæste, Christiane Kruse; Azqueta, Amaya; Tavares, Ana M.; Spyropoulou, Anastasia; Solhaug, Anita; Olsen, Ann-Karin; Vettorazzi, Ariane; Mertens, Birgit; Zegura, Bojana; Streel, Camille; Ndiaye, Dieynaba; Spilioti, Eliana; Dubreil, Estelle; Buratti, Franca Maria; Crudo, Francesco; Eriksen, Gunnar Sundstøl; Snapkow, Igor; Teixeira, João Paulo; Rasinger, Josef D.; Sanders, Julie; Machera, Kyriaki; Ivanova, Lada; Gaté, Laurent; Le Hegarat, Ludovic; Novak, Matjaz; Smith, Nicola M.; Tait, Sabrina; Fraga, Sónia; Hager, Sonja; Marko, Doris; Braeuning, Albert; Louro, Henriqueta; Silva, Maria João; Dirven, Hubert; Dietrich, JessicaEnniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.
- HBM4EU E-waste study – An untargeted metabolomics approach to characterize metabolic changes during E-waste recyclingPublication . Kozlowska, Lucyna; Viegas, Susana; Scheepers, Paul T.J.; Duca, Radu C.; Godderis, Lode; Martins, Carla; Krzesimir, Ciura; Jagiello, Karolina; Silva, Maria João; Mahiout, Selma; Mārtiņsone, Inese; Matisāne, Linda; van Nieuwenhuyse, An; Puzyn, Tomasz; Sijko-Szpanska, Monika; Verdonck, Jelle; Santonen, Tiina; HBM4EU E-waste Study TeamE-waste contains hazardous chemicals that may be a direct health risk for workers involved in recycling. We conducted an untargeted metabolomics analysis of urine samples collected from male e-waste processing workers to explore metabolic changes associated with chemical exposures in e-waste recycling in Belgium, Finland, Latvia, Luxembourg, the Netherlands, Poland, and Portugal. Questionnaire data and urine samples were obtained from workers involved in the processing of e-waste (sorting, dismantling, shredding, pre-processing, metal, and non-metal processing), as well as from controls with no known occupational exposure. Pre- and post-shift urine samples were collected and analysed using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS). A total of 32 endogenous urinary metabolites were annotated with a Variable Importance in Projection (VIP) above 2, indicating that e-waste recycling is mainly associated with changes in steroid hormone and neurotransmitter metabolism, energy metabolism, bile acid biosynthesis, and inflammation. The highest VIP was observed for dopamine-o-quinone, which is linked to Parkinson’s disease. These and other changes in metabolism in workers employed in the processing of e-waste need further verification in targeted studies.
- HBM4EU e-waste study – Occupational exposure assessment to chromium, cadmium, mercury and lead during e-waste recyclingPublication . Leese, Elizabeth; Verdonck, Jelle; Porras, Simo P.; Airaksinen, Jaakko; Duca, Radu C.; Galea, Karen S.; Godderis, Lode; Janasik, Beata; Mahiout, Selma; Martins, Carla; Mārtiņsone, Inese; Ani, Maria Mirela; van Nieuwenhuyse, An; Scheepers, Paul T.J.; Silva, Maria João; Viegas, Susana; Santonen, Tiina; HBM4EU E-waste Study TeamProcessing of electronic waste (e-waste) causes the release of toxic substances which may lead to occupational exposure. The study aimed to gather information on potential occupational exposure during e-waste recycling, with a focus on biomonitoring of chromium, cadmium, mercury and lead. In eight European countries, 195 workers involved in the recycling of lead batteries, white goods, brown goods and metals and plastics were studied. These workers were compared to 73 controls with no direct involvement of e-waste recycling or other metal processing activities. The samples collected consisted of urine, blood and hair samples, along with personal air samples, hand wipes, settled dust samples and contextual information. Chromium, cadmium, mercury and lead was measured in urine, hair, air samples, hand wipes and settled dust; cadmium and lead in whole blood and chromium in red blood cells. Results showed that lead exposure is of concern, with workers from all five types of e-waste showing exposure, with elevated measurements in all matrices. Internal exposure markers were positively correlated with markers of external exposure, indicating workers are not adequately protected. Exposure to mercury and cadmium was also observed but to a much lesser extent with raised cadmium concentrations in urine and blood of all workers when compared to controls and raised mercury concentrations were found in brown goods workers when compared to controls. This study has highlighted exposure concerns when processing e-waste, particularly for lead across all waste categories studied, indicating a need for improved control measures in this sector.
- Guidance on minimum information requirements (MIR) from designing to reporting human biomonitoring (HBM)Publication . Jeddi, Maryam Zare; Galea, Karen S.; Ashley-Martin, Jillian; Nassif, Julianne; Pollock, Tyler; Poddalgoda, Devika; Kasiotis, Konstantinos M.; Esteban-López, Marta; Chung, Ming Kei; Kil, Jihyon; Jones, Kate; Covaci, Adrian; Ait Bamai, Yu; Fernandez, Mariana F.; Pasanen Kase, Robert; Louro, Henriqueta; Silva, Maria J.; Santonen, Tiina; Katsonouri, Andromachi; Castaño, Argelia; Quirós-Alcalá, Lesliam; Argelia Castaño; Lesliam Quirós-Alcalá; Lin, Elizabeth Ziying; Pollitt, Krystal; Ana Virgolino; Virgolino, Ana; Scheepers, Paul T.J; Mustieles, Vicente; Cañas-Portilla, Ana Isabel; Viegas, Susana; von Goetz, Natalie; Sepai, Ovnair; Bird, Emily; Gӧen, Thomas; Fustinoni, Silvia; Ghosh, Manosij; Dirven, Hubert; Kwon, Jung-Hwan; Carignan, Courtney; Mizuno, Yuki; Ito, Yuki; Xia, Yankai; Shoji F. Nakayama; Nakayama, Shoji F.; Makris, Konstantinos C.; Parsons, Patrick J.; Gonzales, Melissa; Bader, Michael; Dusinska, Maria; Menouni, Aziza; Duca, Radu Corneliu; Chbihi, Kaoutar; El Jaafari, Samir; Godderis, Lode; van Nieuwenhuyse, An; Qureshi, Asif; Ali, Imran; Costa Trindade, Carla; Teixeira, Joao Paulo; Bartonova, Alena; Tranfo, Giovanna; Audouze, Karine; Verpaele, Steven; LaKind, Judy; Mol, Hans; Bessems, Jos; Magagna, Barbara; Nasution Waras, Maisarah; Connolly, Alison; Nascarella, Marc; Yang, Wonho; Huang, Po-Chin; Heussen, Henri; Goksel, Ozlem; Yunesian, Masud; Yeung, Leo W.Y.; Souza, Gustavo; Vekic, Ana Maria; Haynes, Erin N.; Hopf, Nancy B.Human biomonitoring (HBM) provides an integrated chemical exposures assessment considering all routes and sources of exposure. The accurate interpretation and comparability of biomarkers of exposure and effect depend on harmonized, quality-assured sampling, processing, and analysis. Currently, the lack of broadly accepted guidance on minimum information required for collecting and reporting HBM data, hinders comparability between studies. Furthermore, it prevents HBM from reaching its full potential as a reliable approach for assessing and managing the risks of human exposure to chemicals. The European Chapter of the International Society of Exposure Science HBM Working Group (ISES Europe HBM working group) has established a global human biomonitoring community network (HBM Global Network) to develop a guidance to define the minimum information to be collected and reported in HBM, called the “Minimum Information Requirements for Human Biomonitoring (MIR-HBM)”. This work builds on previous efforts to harmonize HBM worldwide. The MIR-HBM guidance covers all phases of HBM from the design phase to the effective communication of results. By carefully defining MIR for all phases, researchers and health professionals can make their HBM studies and programs are robust, reproducible, and meaningful. Acceptance and implementation of MIR-HBM Guidelines in both the general population and occupational fields would improve the interpretability and regulatory utility of HBM data. While implementation challenges remain—such as varying local capacities, and ethical and legal differences at the national levels, this initiative represents an important step toward harmonizing HBM practice and supports an ongoing dialogue among policymakers, legal experts, and scientists to effectively address these challenges. Leveraging the data and insights from HBM, policymakers can develop more effective strategies to protect public health and ensure safer working environments.
- Occupational exposure to wildland firefighting and its effects on systemic DNA damagePublication . Esteves, Filipa; Madureira, Joana; Costa, Carla; Pires, Joana; Barros, Bela; Alves, Sara; Vaz, Josiana; Oliveira, Marta; Slezakova, Klara; Fernandes, Adília; Pereira, Maria do Carmo; Morais, Simone; Valdiglesias, Vanessa; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeBackground: Portugal is among the European Union countries more devastated by forest fires. Wildland firefighters are at the forefront of this battle, facing exposure to a wide range of harmful pollutants. Epidemiological studies have highlighted a potential link between occupational firefighting exposure and several diseases, including cancer. To date, very few studies have explored the biological mechanisms associated with such exposure. The present longitudinal study aims to assess changes in early effect biomarkers following wildland firefighters’ occupational exposure to a real wildfire event. Methods: Paired blood samples from 59 healthy Portuguese wildland firefighters were collected at two different time points: before wildfire season and after a fire event during wildfire season. Sociodemographic variables (e.g., age, sex) and work-related factors (e.g., years of service) were assessed via a self-reported questionnaire. Levels of early effect biomarkers, such as primary DNA damage and oxidative DNA damage (oxidised purines) were assessed via comet assay. DNA double-strand breaks (DSBs) were evaluated by phosphorylated H2AX (γH2AX). Moreover, hydroxylated polycyclic aromatic hydrocarbon metabolites (OHPAHs) and metal(loid)s were quantified in urine samples. The influence of urinary OHPAHs, urinary metal(loid)s, and other exposure-related factors (e.g., firefighting duration) on changes (Δ) in early effect biomarkers (post-vs. baseline levels) was investigated. Results: Firefighting activities led to a significant increase in both primary DNA damage and oxidative DNA damage by 22 % (95 % CI: 1.11–1.35; p < 0.05) and 23 % (95 % CI: 1.04–1.45; p < 0.05), respectively. Results from linear regression revealed that per each unit increase of urinary 2-hydroxyfluorene (2-OHFlu) (μmol/mol creatinine), the risk of ⧍ oxidative DNA damage increased by 20 % [FR: 1.20 (1.09–1.32); p < 0.01]. Additionally, each unit increase in urinary cesium (Cs) (μg/L) resulted in a significant 4 % increase in Δ primary DNA damage [FR: 1.04 (1.01–1.06); p < 0.05] and a 3 % increase in Δ oxidative DNA damage [FR: 1.03 (1.01–1.05); p < 0.05]. Post-exposure levels of γH2AX were significantly correlated with urinary 2-OHFlu levels assessed after firefighting (r = 0.30; p < 0.05). Furthermore, exposure duration and reported breathing difficulties during firefighting were significantly associated with increased levels of primary DNA damage. Conclusion: Results obtained provide insights into the potential human health effects of wildland firefighting occupational exposure at the genetic and molecular levels, offering new and important mechanistic data. These findings are crucial for implementing health and safety measures, recommendations, and best practices to mitigate occupational risks and protect the health of wildland firefighters.
- Seasonality of mortality under climate change: a multicountry projection studyPublication . Madaniyazi, Lina; Armstrong, Ben; Tobias, Aurelio; Mistry, Malcolm N.; Bell, Michelle L.; Urban, Aleš; Kyselý, Jan; Ryti, Niilo; Cvijanovic, Ivana; Ng, Chris Fook Sheng; Roye, Dominic; Vicedo-Cabrera, Ana Maria; Tong, Shilu; Lavigne, Eric; Íñiguez, Carmen; das Neves Pereira da Silva, Susana; Madureira, Joana; Jaakkola, Jouni J.K.; Sera, Francesco; Honda, Yasushi; Gasparrini, Antonio; Hashizume, Masahiro; Multi-Country Multi-City Collaborative Research NetworkBackground: Climate change can directly impact temperature-related excess deaths and might subsequently change the seasonal variation in mortality. In this study, we aimed to provide a systematic and comprehensive assessment of potential future changes in the seasonal variation, or seasonality, of mortality across different climate zones. Methods: In this modelling study, we collected daily time series of mean temperature and mortality (all causes or non-external causes only) via the Multi-Country Multi-City Collaborative (MCC) Research Network. These data were collected during overlapping periods, spanning from Jan 1, 1969 to Dec 31, 2020. We projected daily mortality from Jan 1, 2000 to Dec 31, 2099, under four climate change scenarios corresponding to increasing emissions (Shared Socioeconomic Pathways [SSP] scenarios SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). We compared the seasonality in projected mortality between decades by its shape, timings (the day-of-year) of minimum (trough) and maximum (peak) mortality, and sizes (peak-to-trough ratio and attributable fraction). Attributable fraction was used to measure the burden of seasonality of mortality. The results were summarised by climate zones. Findings: The MCC dataset included 126 809 537 deaths from 707 locations within 43 countries or areas. After excluding the only two polar locations (both high-altitude locations in Peru) from climatic zone assessments, we analysed 126 766 164 deaths in 705 locations aggregated in four climate zones (tropical, arid, temperate, and continental). From the 2000s to the 2090s, our projections showed an increase in mortality during the warm seasons and a decrease in mortality during the cold seasons, albeit with mortality remaining high during the cold seasons, under all four SSP scenarios in the arid, temperate, and continental zones. The magnitude of this changing pattern was more pronounced under the high-emission scenarios (SSP3-7.0 and SSP5-8.5), substantially altering the shape of seasonality of mortality and, under the highest emission scenario (SSP5-8.5), shifting the mortality peak from cold seasons to warm seasons in arid, temperate, and continental zones, and increasing the size of seasonality in all zones except the arid zone by the end of the century. In the 2090s compared with the 2000s, the change in peak-to-trough ratio (relative scale) ranged from 0·96 to 1·11, and the change in attributable fraction ranged from 0·002% to 0·06% under the SSP5-8.5 (highest emission) scenario. Interpretation: A warming climate can substantially change the seasonality of mortality in the future. Our projections suggest that health-care systems should consider preparing for a potentially increased demand during warm seasons and sustained high demand during cold seasons, particularly in regions characterised by arid, temperate, and continental climates.
- Air pollution mixture complexity and its effect on PM2.5-related mortality: A multicountry time-series study in 264 citiesPublication . Masselot, Pierre; Kan, Haidong; Kharol, Shailesh K; Bell, Michelle L.; Sera, Francesco; Lavigne, Eric; Breitner, Susanne; das Neves Pereira da Silva, Susana; Burnett, Richard T.; Gasparrini, Antonio; Brook, Jeffrey R.; MCC Collaborative Research NetworkBackground: Fine particulate matter (PM2.5) occurs within a mixture of other pollutant gases that interact and impact its composition and toxicity. To characterize the local toxicity of PM2.5, it is useful to have an index that accounts for the whole pollutant mix, including gaseous pollutants. We consider a recently proposed pollutant mixture complexity index (PMCI) to evaluate to which extent it relates to PM2.5 toxicity. Methods: The PMCI is constructed as an index spanning seven different pollutants, relative to the PM2.5 levels. We consider a standard two-stage analysis using data from 264 cities in the Northern Hemisphere. The first stage estimates the city-specific relative risks between daily PM2.5 and all-cause mortality, which are then pooled into a second-stage meta-regression model with which we estimate the effect modification from the PMCI. Results: We estimate a relative excess risk of 1.0042 (95% confidence interval: 1.0023, 1.0061) for an interquartile range increase (from 1.09 to 1.95) of the PMCI. The PMCI predicts a substantial part of within-country relative risk heterogeneity with much less between-country heterogeneity explained. The Akaike information criterion and Bayesian information criterion of the main model are lower than those of alternative meta-regression models considering the oxidative capacity of PM2.5 or its composition. Conclusions: The PMCI represents an efficient and simple predictor of local PM2.5-related mortality, providing evidence that PM2.5 toxicity depends on the surrounding gaseous pollutant mix. With the advent of remote sensing for pollutants, the PMCI can provide a useful index to track air quality.
- Baseline data and associations between urinary biomarkers of polycyclic aromatic hydrocarbons, blood pressure, hemogram, and lifestyle among wildland firefightersPublication . Barros, Bela; Paiva, Ana Margarida; Oliveira, Marta; Alves, Sara; Esteves, Filipa; Fernandes, Adília; Vaz, Josiana; Slezakova, Klara; Costa, Solange; Teixeira, João Paulo; Morais, SimoneIntroduction: Available literature has found an association between firefighting and pathologic pathways leading to cardiorespiratory diseases, which have been linked with exposure to polycyclic aromatic hydrocarbons (PAHs). PAHs are highlighted as priority pollutants by the European Human Biomonitoring Initiative in occupational and non-occupational contexts. Methods: This cross-sectional study is the first to simultaneously characterize six creatinine-adjusted PAHs metabolites (OHPAHs) in urine, blood pressure, cardiac frequency, and hemogram parameters among wildland firefighters without occupational exposure to fire emissions (> 7 days), while exploring several variables retrieved via questionnaires. Results: Overall, baseline levels for total OHPAHs levels were 2 to 23-times superior to the general population, whereas individual metabolites remained below the general population median range (except for 1-hydroxynaphthalene+1-hydroxyacenaphtene). Exposure to gaseous pollutants and/or particulate matter during work-shift was associated with a 3.5-fold increase in total OHPAHs levels. Firefighters who smoke presented 3-times higher total concentration of OHPAHs than non-smokers (p < 0.001); non-smoker females presented 2-fold lower total OHPAHs (p = 0.049) than males. 1-hydroxypyrene was below the recommended occupational biological exposure value (2.5 μg/L), and the metabolite of carcinogenic PAH (benzo(a)pyrene) was not detected. Blood pressure was above 120/80 mmHg in 71% of subjects. Firefighters from the permanent intervention team presented significantly increased systolic pressure than those who performed other functions (p = 0.034). Tobacco consumption was significantly associated with higher basophils (p = 0.01–0.02) and hematocrit (p = 0.03). No association between OHPAHs and blood pressure was found. OHPAHs concentrations were positively correlated with monocyte, basophils, large immune cells, atypical lymphocytes, and mean corpuscular volume, which were stronger among smokers. Nevertheless, inverse associations were observed between fluorene and pyrene metabolites with neutrophils and eosinophils, respectively, in non-smokers. Hemogram was negatively affected by overworking and lower physical activity. Conclusion: This study suggests possible associations between urinary PAHs metabolites and health parameters in firefighters, that should be further assessed in larger groups.
- Cumulus cell DNA damage linked to fertilization success in females with an ovulatory dysfunction phenotypePublication . Rodrigues, Bárbara; Sousa, Vanessa; Esteves, Filipa; Vale-Fernandes, Emídio; Costa, Solange; Sousa, Daniela; Brandão, Raquel; Leal, Carla; Pires, Joana; Gaivão, Isabel; Teixeira, João Paulo; Nogueira, António J.A.; Jorge, PaulaIntracytoplasmic sperm injection (ICSI) is a widely used technique in fertility centers. ICSI success depends on both nuclear and cytoplasmic oocyte maturation. Cumulus cells, which surround the oocytes, play a pivotal role in oocyte competence. However, the significance of DNA damage in cumulus cells as a marker of fertilization success remains largely unexplored. This study aims to investigate the relationship between DNA damage in cumulus cells of females undergoing ICSI, and oocyte competence, with a focus on in vitro fertilization (IVF) outcomes. We employed the alkaline comet assay to assess DNA damage levels (%TDNA) in cumulus cells and whole blood from 22 potentially fertile females and 35 infertile females, including 20 with an ovulatory disfunction phenotype. Our results revealed significant differences between the levels of %TDNA in cumulus cells and blood. Females with an ovulatory dysfunction phenotype exhibited higher levels of %TDNA in cumulus cells compared to potentially fertile females. Additionally, within the group of females with ovulatory dysfunction, a significant correlation was observed between %TDNA levels and the number of oocytes with two pronuclei. Our findings suggest that blood does not accurately reflect DNA damage in cumulus cells, which was correlated with the fertilization success in females with ovulatory dysfunction. High levels of %TDNA in cumulus cells were associated with a higher likelihood of successful fertilization. Moreover, our results imply that low levels of %TDNA may be linked to oocytes that fail to complete maturation and, consequently, do not fertilize (oocytes with zero pronuclei). Further research with larger cohorts is necessary to validate these findings and to explore potential applications in female fertility. However, our study provides evidence that DNA damage in cumulus cells may serve as a valuable biomarker for predicting fertilization success and oocyte competence.
- Biomonitoring of firefighters’ exposure to priority pollutant metal(loid)s during wildland fire combat missions: Impact on urinary levels and health risksPublication . Paiva, Ana Margarida; Barros, Bela; Azevedo, Rui; Oliveira, Marta; Alves, Sara; Esteves, Filipa; Fernandes, Adília; Vaz, Josiana; Alves, Maria José; Slezakova, Klara; Pereira, Maria do Carmo; Teixeira, João Paulo; Costa, Solange; Almeida, Agostinho; Morais, SimoneWildland firefighters are exposed to metal(loid)s released during wildfires through vegetation combustion, which also promotes remobilization of accumulated anthropogenic metal(loid)s. Studies biomonitoring metal(loid)s exposure promoted exclusively by wildfire suppression activities are lacking. This work aimed to characterize, for the first time, the impact of real-life wildland firefighting operations on urinary levels of priority pollutant metal(loid)s [14 included in ATSDR, 11 in USEPA, and 4 in Human Biomonitoring for Europe Initiative priority lists] in firefighters. Spot urines were sampled pre-exposure (105 non-smokers, 76 smokers) and post-exposure to firefighting activities (20 non-smokers, 25 smokers); among those, paired samples were collected from 14 non-smoking and 24 smoking firefighters. Smokers displayed significantly higher baseline levels of zinc (28 %), lithium (29 %), cadmium (55 %), rubidium (13 %), and copper (20 %) than non-smokers. Following wildfire suppression, the concentration of the WHO potentially toxic metal(loid)s rose from 2 % to 3 % in smokers and 2 % to 5 % in non-smokers (up to 4 % for all firefighters and up to 5 % in paired samples). Levels of nickel (33-53 %), antimony (45-56 %), and cesium (40-47 %) increased significantly post-exposure in non-smokers (in all firefighters and in paired samples), whose urinary concentrations were generally more impacted by wildfire emissions than those of smokers. Arsenic (80 %) displayed the only significant increase post-exposure in smokers, being the best discriminant of exposure to wildfire emissions in these subjects. Significant positive correlations were found for age and/or career length with cadmium, lead, barium, strontium, and mercury, and for body mass index with arsenic. The reference/guidance values were exceeded for arsenic, zinc, cesium, nickel, antimony, cadmium, lead, thallium, mercury, copper, and cobalt in 1-90 % of firefighters suggesting augmented health risks due to wildfire combating and emphasizing the need of mitigation strategies. This study also provides biomonitoring data to help setting reference values for the occupationally exposed part of population.