Centro Nacional de Sanidad Ambiental (CNSA)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/19610

El Centro Nacional de Sanidad Ambiental (CNSA) es el órgano científico-técnico del Instituto de Salud Carlos III, especializado en los aspectos sanitarios de los problemas derivados de la contaminación medioambiental. Su finalidad primordial es la caracterización del riesgo potencial ante contaminantes ambientales a los que está expuesta la población. Fue creado mediante Decreto 252/1974, de 25 de enero y posteriormente, adscrito al Instituto de Salud Carlos III (Ley 14/1986). Sus laboratorios cuentan con una extensión de más de 3 000 m2, dotados con instrumentación de última tecnología. Funciona bajo un sistema de calidad UNE-EN ISO/IEC 17025 y está acreditado por la Entidad Nacional de Acreditación (ENAC) para 186 ensayos, distribuidos en las distintas unidades funcionales: Contaminación Atmosférica, Contaminación Hídrica y Microbiología Ambiental, Toxicología Ambiental y Radioprotección.

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High prevalence of azole resistance among environmental isolates from outdoor air in Madrid, Spain.
(Frontiers Media, 2026-01-23) Soto-Debrán, Juan Carlos; Sanchez Iñigo, Francisco Javier; Calvo-López, Alejandro B; Alguacil-Cuéllar, Laura; Hrynzovska, Anastasiia A; Mellado, Emilia; Garcia Dos Santos-Alves, Saul; Alastruey-Izquierdo, Ana; Instituto de Salud Carlos III
Introduction: Aspergillus fumigatus has been designated by the World Health Organization (WHO) as a critical fungal pathogen. Its spores are commonly present in the air and are inhaled daily. Azoles are the first-line treatment for Aspergillus infections, but the emergence of resistance is a growing concern. However, limited data exist on the occurrence of azole-resistant A. fumigatus in the outdoor environment in Spain. Methods: This study aimed to investigate the prevalence of azole-resistant A. fumigatus isolates in outdoor air at two distinct locations in Madrid. We characterized the isolates using TRESPERG genotyping and examined the underlying molecular mechanisms responsible for azole resistance development. Results: Azole-resistant A. fumigatus isolates were found in 55% of the 20 air samples collected. Among the 200 A. fumigatus isolates analyzed, 38.5% were azole resistant and were classified into 10 different genotypes. Notably, the TR34/L98H mutation in Cyp51A was found in 77% of the resistant isolates, while 23% showed no mutations in the screened targets (cyp51A, cyp51B, or hmg1). Discussion: This study revealed a high prevalence of azole-resistant A. fumigatus in outdoor environmental air, with the TR34/L98H mutation being the main mechanism of azole resistance. A close genetic relationship was observed among the resistant isolates. This research underscores the need for continued monitoring of environmental azole-resistant A. fumigatus isolates and highlights the importance of understanding genetic diversity and resistance mechanisms to develop effective strategies for fungal infection control.
Raw data for nanoplastic toxicity experiments in Daphnia magna: reproduction, morphology and behavior.
(Instituto de Salud Carlos III (ISCIII). Centro Nacional de Sanidad Ambiental (CNSA), 2026-03-24) Torres-Ruiz, Mónica
[EN] This project investigates the effects of polystyrene nanoplastics on aquatic organisms using Daphnia magna as a model, aiming to understand how individual-level exposure impacts key biological functions and may have broader ecological implications. [ES] Este proyecto investiga los efectos de nanoplásticos de poliestireno en organismos acuáticos utilizando Daphnia magna como modelo, con el objetivo de comprender cómo la exposición a nivel individual puede afectar funciones biológicas clave y tener implicaciones ecológicas.
Metodología científica y nuevas perspectivas de la evaluación de riesgos de sustancias químicas en sanidad ambiental.
(Instituto de Salud Carlos III (ISCIII). Centro Nacional de Sanidad Ambiental (CNSA), 2026-03) Domínguez-Morueco, Noelia; Fernandez Agudo, Ana; González-Caballero, MCarmen; Tarazona, Jose; Unidad de Evaluación de Riesgos, Centro Nacional de Sanidad Ambiental (CNSA)
Este libro surge para ofrecer una visión integrada y actualizada de la metodología científica aplicada a la evaluación de riesgos de sustancias químicas, abordando estos retos desde una perspectiva científica rigurosa, pero también práctica. Uno de sus principales valores, en línea con la ciencia de la evaluación de riesgos, es su enfoque multidisciplinar, que integra conocimientos procedentes de todos los ámbitos relacionados. Esta visión transversal refleja la realidad del trabajo en Sanidad Ambiental, donde la toma de decisiones exige una comprensión global de los procesos que vinculan las fuentes de contaminación, las vías de exposición, la toxicocinética de los químicos, los eventos tóxicos que se producen, la respuesta de cada organismo/ecosistema y en último término, los efectos sobre la salud humana y el medio ambiente, poniendo de manifiesto, la importancia de la evaluación de riesgos como instrumento clave para la toma de decisiones informadas y la formulación de políticas públicas eficaces. Por ello, confiamos en que se convierta en referencia para quienes trabajan, investigan y se forman en el ámbito de la Sanidad Ambiental, contribuyendo a mejorar la comprensión de los riesgos químicos y a reforzar las estrategias de prevención y protección de la salud.
Sensitive Instrumental Method for Quantitative Determination of High-Brominated Flame Retardants in Human Serum Samples
(Oxford University Press, 2023-05-12) Grande, Cristina; Castaño, Argelia; Ramos, Juan Jose
Background: High-brominated flame retardants (BFRs) can be released into the environment from consumer products, such as electric and electronic equipment, and enter the human body by different pathways. Because of their toxicity and the regulations, it is very relevant to know their levels and trends in human samples. However, chromatographic serum analysis of some of these compounds represents nowadays a challenge in the general population. Objective: To optimize and validate an instrumental method based on gas chromatography coupled to mass spectrometry, which, together with a simple sample preparation procedure, allows the analysis of decabromodiphenyl ether (BDE-209), decabromodiphenyl ethane (DBDPE), and tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-DBPE) in human serum samples from the general population. Method: To minimize the high degradation during instrumental analysis, GC parameters such as injection volumes, carrier flow rates, and column lengths were assessed and optimized. This instrumental approach in combination with solid-phase extraction (SPE) followed by multilayer silica gel column purification allowed satisfactory analysis using only 1 mL of serum. Results: The performance of the complete method was evaluated at three spiking levels, 0.01, 0.05, and 0.2 ng/mL. Recoveries in the range 87-108% were obtained whereas the relative standard deviation in interday measurements, were, in general, lower than 19%. Limits of detection were in the range of 0.0045-0.0070 ng/mL. The optimized procedure was successfully applied to the determination of the investigated pollutants in real human samples of general population. Conclusions: The proposed method could contribute to the inclusion of these environmental pollutants in human biomonitoring (HBM) studies, increasing the knowledge of levels and trends in the general population. Highlights: GC-MS parameters optimization to minimize instrumental analytes degradation. Successful application to human serum samples from the general population. Tetrabromobisphenol A bis(2,3-dibromopropyl ether) human serum levels are reported for the first time.
Associations of internal persistent organic pollutant levels with sex hormones: An analysis by sex and menopausal status in a Spanish cohort
(Elsevier, 2025-07) Pérez-Díaz, Celia; Echeverría, Ruth; Pérez-Carrascosa, Francisco M.; Salcedo-Bellido, Inmaculada; Requena, Pilar; Barrios-Rodríguez, Rocío; Ramos, Juan Jose; Olea, Nicolás; Fernández, Mariana F.; Martín-Olmedo, Piedad; Arrebola, Juan Pedro
The aim of this study was to investigate associations between human exposure to persistent organic pollutants and sex hormone levels. The study population (n = 253) was a subsample of GraMo adult cohort, recruited in 2003-2004 in two hospitals from Granada, Spain. Exposure was estimated by analyzing samples of adipose tissue (3 organochlorine pesticides and 3 polychlorinated biphenyls) and serum (4 per- and polyfluoroalkyl substances). Data analyses included robust linear regression and weighted quantile sum regression. In men, PFNA (positively) and PCB-138 (negatively) were associated with testosterone. In premenopausal women, OCPs and PCBs were negatively associated with estradiol and SHBG. PFHxS was inversely related to luteinizing hormone. Additionally, PCB-153 and -180 was positively associated with testosterone. The mixture of PCBs/OCPs was positively associated with testosterone in women and with FSH in men. Our results highlight the potential of chemical mixture exposure to alter sex hormone homeostasis, depending on sex and menopausal status.
Urban Observatory for Multi-participatory Enhancement of Health and Wellbeing (URBANOME). Data Management Plan V2.0 (DMP)
(European Comission, 2023-02) Aristotle University of Thessaloniki (AUTH); University of Stuttgart (USTUT); Ambiente Italia (AMBIT); Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT); Robert Gordon University (RGU); Vilabs LTD (VIL); UPCOM BVBA; Institut Jozef Stefan (JSI); European Network of Living Labs IVZW (ENoLL); ADDMA; Aarhus Universitet (AU); Istituto Universitario di Studi Superiori ( I.U.S.S.) di Pavia; ENVE.X Single Member PC; Institut National de la Sante et de la Recherche Medicale (INSERM); Comune di Milano (CdM); Instituto de Salud Carlos III (ISCIII); Unión Europea. Comisión Europea. H2020
This document is the second version of the DMP (deliverable D10.3), delivered in Month 24 of the project. It includes updated information about the datasets produced by the project according to the FAIR principles to make the data findable, accessible, interoperable and reusable.
Partnership for the Assessment of Risks from Chemicals (PARC). Data Management Plan V1.0 (DMP)
(European Comission, 2022-10-31) van de Brug, Fred; Stierum, Rob; Partnership for the Assessment of Risks from Chemicals (PARC); Unión Europea. Comisión Europea. Horizonte Europa; Pedraza-Diaz, Susana, reviewer
PARC is the European partnership for the development of next generation chemical risk assessment methods. In the context of Open Science, the PARC objective OO10 is to implement FAIR data practices and enhance innovation in complex data analysis for chemicals risk assessment. PARC will develop a FAIR data culture enabling open science and provide the technical methods, tools and infrastructure for effective exchange of data and information. Innovation in risk assessment and risk management which is required for the transition to next generation risk assessment can only be achieved in an open and collaborative way. FAIR and open data sharing according to the ‘as open as possible, as closed as necessary’ principle will be the default for PARC and will be applied to all research outputs (including reports, data, software, guidelines, method descriptions, formats, templates, semantic artefacts, ontologies, vocabularies etc.). This deliverable presents version 1 of the PARC overarching data management plan (DMP). The domain specific guidance in version 1 is based on the analysis of DMP’s of a selection of projects covering research data domains PARC is concerned with: exposome research, biomonitoring, innovations in (eco-)toxicological hazard assessment, e.g., via in vitro new approach methodologies, nanomaterial safety and metabolism disrupting chemicals. The DMP contains guidance to support PARC researchers in multiple ways: by providing additional information; by providing generic texts and by suggesting possible domain specific or generic choices.
Emerging Pollutants in Chinstrap Penguins and Krill from Deception Island (South Shetland Islands, Antarctica)
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-06-29) Motas, Miguel; Jerez-Rodríguez, Silvia; Veiga-del-Baño, José Manuel; Ramos, Juan Jose; Oliva, José; Cámara, Miguel Ángel; Andreo-Martínez, Pedro; Corsolini, Simonetta; Ministerio de Ciencia e Innovación (España)
This study aimed to evaluate the presence of emerging pollutants [perfluorinated compounds, phthalates and bisphenol A (BPA)] in chinstrap penguins (Pygoscelis antarctica) and krill (Euphausia superba) from Deception Island (South Shetland Islands, Antarctica) to provide data on the occurrence of emerging pollutants in Antarctica. For this purpose, thirty-four samples were studied, including four samples of adult tissue and six samples of chick tissue, as well as krill samples from the area. The selected samples were subjected to extraction processes and subsequent analytical determination of perfluorooctane sulfonate, perfluorooctanoic acid, di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate and BPA using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry. Our results highlight that the analyzed organic pollutants, except for BPA, are clearly present in Pygoscelis antarctica and Euphausia superba from Deception Island.
PCBs in Chinstrap Penguins from Deception Island (South Shetland Islands, Antarctica)
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-24) Motas, Miguel; Jerez-Rodríguez, Silvia; Veiga-Del-Baño, José Manuel; Ramos, Juan Jose; Oliva, José; Cámara, Miguel Ángel; Andreo-Martínez, Pedro; Corsolini, Simonetta; Ministerio de Ciencia e Innovación (España)
The aim of this study was to evaluate the concentration of polychlorinated biphenyls (PCBs) in chinstrap penguins (Pygoscelis antarctica) and krill (Euphausia superba) from Deception Island (South Shetland Islands, Antarctica) to provide additional data of the PCB presence in Antarctica. To this end, 34 samples of different tissues corresponding to four adult specimens and six chicks, and krill from the area were studied. The selected samples were analyzed for the determination of 27 congeners of PCBs by gas chromatography. Adult specimens accumulated PCBs mainly in the liver (33%, 1330.82 ± 733.69 pg·g-1 wet weight, w.w.) and muscle (25%, 1029.73 ± 823.4 pg·g-1 w.w.), whereas the brain showed the highest levels in chicks (36%, 1215.83 ± 955.19 pg·g-1 w.w.). Regarding krill, our results were five to eight times lower than the levels found in krill from King George Island and from the Ross Sea. Further, a distribution analysis of PCBs in penguins according to Regulation 2013/39/UE and Commission Regulation (EU) No 277/2012 was also performed, and PCBs were categorized into three groups (dioxin-like-mono-ortho, non-dioxin-like-indicators, and others-non-dioxin-like). The data indicate that the content of the other group was generally higher than that of the other two PCB groups for both adults and chicks. Notably, the liver consistently exhibited the highest proportion of the other group.
Short-Term Ozone Exposure and Daily Mortality in Suburban and Rural Areas of Southern Europe
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-20) Doronzo, Maria Angela; Martinez Fernandez, José Ramón; Gomez-Barroso, Diana; Alonso-Colón, María; Nuñez-Corcuera, Beatriz; Ramis, Rebeca; Unión Europea. Comisión Europea. H2020; Unión Europea. Comisión Europea. Horizonte Europa
Ozone (O3) is a major air pollutant with significant health effects, including increased respiratory and cardiovascular mortality. While previous research has largely focused on urban areas, this study assesses the association between maximum 8 h O3 concentrations and non-accidental mortality, including cardiovascular and respiratory mortality, in suburban and rural areas of Spain. We conducted a nationwide time-series analysis across 122 municipalities between April and September 2017 using Poisson regression models and adjusting for daily maximum temperature and provincial variability. Distributed lag models were applied to estimate the cumulative effects of ozone exposure on mortality, considering lags from 1 to 30 days. For each 10 µg/m3 increase in 8 h maximum O3 concentration, a significant increase in all-cause mortality risk of 2.3% was observed, with a peak at lag 2. Cardiovascular mortality increased by 2.4%, also peaking at lag 2, while respiratory mortality showed the strongest association, with a 4.3% rise at lag 1. A secondary mortality risk increase was observed at lags 24–28, suggesting the potential delayed effects of O3 exposure. These findings showed higher risk than those previously reported for urban populations and highlight the need for targeted public health interventions to mitigate the impact of ozone pollution in non-urban populations.
Calibration of Toenail Metal Concentrations for Sample Mass Heterogeneity and Between-Batch Variability: The COMET Approach
(National Institute of Environmental Health Sciences (NIEHS), 2025-04) Pastor-Barriuso, Roberto; Gutiérrez-González, Enrique; Varea-Jiménez, Elena; Gómez-Ariza, José Luis; Castaño-Vinyals, Gemma; Aragonés, Nuria; Molina, Antonio José; Dierssen-Sotos, Trinidad; Fernández-Tardón, Guillermo; Amiano, Pilar; Ederra-Sanz, María; Moreno, Victor; Jiménez-Moleón, José Juan; Molina-Barceló, Ana; Marcos-Gragera, Rafael; Casabonne, Delphine; Alguacil, Juan; Gómez-Gómez, Jesús Humberto; García-Barrera, Tamara; Kogevinas, Manolis; Pollan-Santamaria, Marina; Perez-Gomez, Beatriz; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Scientific Foundation
Background: Toenails are promising biomarkers of long-term metal exposure in epidemiological studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample masses, as well as by substantial variability across laboratory batches. Objectives: We propose a novel modeling approach to calibrate toenail metal concentrations for the heterogeneity in sample masses and the variability between batches. Methods: We developed a heteroscedastic spline mixed model relating sample mass and laboratory batch with measured concentrations, allowing for an average bias in measurements over all batches as a smooth function of sample mass, random variation in mass-related biases across batches, and mass-related heterogeneity in within-batch error variance. The model allowed partitioning the total variance of measured concentrations into the extraneous variances (due to different sample masses and laboratory batches) and the intrinsic variance (resulting from distinct metal exposures). We derived calibrated metal concentrations from the model by removing both sources of extraneous variation and estimating the predicted concentrations had all toenail samples been analyzed in a single batch and of the same mass. We provide the R script COMET (COrrected METals) to fit the proposed model, extract variance components, and calibrate metal concentrations. Results: In a multicase-control study in Spain (MCC-Spain) with toenail determinations for 16 metals in 4,473 incident cases of five common cancers and 3,450 population controls, sample mass and batch accounted for 26%-60% of the total variance of measured concentrations for most metals. In comparison with calibrated concentrations, odds ratios for measured concentrations were biased by > 10% toward or away from the null in one-quarter of the estimated metal-cancer associations. Discussion: The proposed model allows correcting toenail metal concentrations for sample mass heterogeneity and between-batch variability and could be applied to other biological specimens of heterogeneous size, distinct laboratory techniques, and different study designs.
Different Ras isoforms regulate synaptic plasticity in opposite directions
(EMBO Press, 2025-02-21) López-Merino, Esperanza; Fernández-Rodrigo, Alba; Jiang, Jessie G; Gutiérrez-Eisman, Silvia; Fernández de Sevilla, David; Fernández-Medarde, Alberto; Santos, Eugenio; Guerra, Carmen; Barbacid, Mariano; Esteban, José A; Briz, Víctor; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III; Fundación Ramón Areces; Ministerio de Ciencia (España)
The small GTPase Ras is an intracellular signaling hub required for long-term potentiation (LTP) in the hippocampus and for memory formation. Genetic alterations in Ras signaling (i.e., RASopathies) are linked to cognitive disorders in humans. However, it remains unclear how Ras controls synaptic plasticity, and whether different Ras isoforms play overlapping or distinct roles in neurons. Using genetically modified mice, we show here that H-Ras (the most abundant isoform in the brain) does not promote LTP, but instead long-term depression mediated by metabotropic glutamate receptors (mGluR-LTD). Mechanistically, H-Ras is activated locally in spines during mGluR-LTD via c-Src, and is required to trigger Erk activation and de novo protein synthesis. Furthermore, H-Ras deletion impairs object recognition as well as social and spatial memory. Conversely, K-Ras is the isoform specifically required for LTP. This functional specialization correlates with a differential synaptic distribution of the two isoforms H-Ras and K-Ras, which may have important implications for RASopathies and cognitive function.
Particulate Matter Exposure during Pregnancy and Childhood Leukemia Incidence
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-06-24) Sanz Olea, Enrique; Ojeda Sánchez, Carlos; Guxens, Mònica; Cañete, Adela; Pardo Romaguera, Elena; Gomez-Barroso, Diana; García-Pérez, Javier; Nuñez-Corcuera, Beatriz; Ortega-García, Juan Antonio; Ramis, Rebeca; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública)
Leukemia is the most common childhood cancer and its etiology could be related to various environmental contaminants such as particulate matter (PM). The objective of our study is to evaluate the potential association between exposure to PM during pregnancy and the incidence of childhood leukemia. We established a population-based nationwide cohort using the Spanish Birth Registry Statistics database of the National Statistics Institute. We used spatiotemporal land use random forest models to estimate the concentrations of PM10 and PM2.5 for the entire pregnancy and by trimesters. We conducted logistic regression analyses adjusted for various covariates. In addition, we fitted generalized additive models (GAMs) to estimate the non-linear relationship between PM levels and leukemia incidence. The study included 3,112,123 children and 1066 cases of leukemia. The results for the continuous variable of PM10 exposure levels suggested an increased risk of childhood leukemia to be associated with higher exposure. The results for the categorized PM10 variable suggest an increased risk of childhood leukemia among pregnant women whose exposure levels were higher than the median (third and fourth quartiles). The results for PM2.5 were weaker. We found association between exposure to PM10 during pregnancy and an increased risk of childhood leukemia. Our findings indicate that public health interventions should aim to reduce air pollution to lower the incidence of childhood leukemia.
Exposure to bisphenol A in European women from 2007 to 2014 using human biomonitoring data - The European Joint Programme HBM4EU
(Elsevier, 2024-08) Tagne-Fotso, Romuald; Riou, Margaux; Saoudi, Abdessattar; Zeghnoun, Abdelkrim; Frederiksen, Hanne; Berman, Tamar; Montazeri, Parisa; Andersson, Anna-Maria; Rodriguez-Martin, Laura; Åkesson, Agneta; Berglund, Marika; Biot, Pierre; Castaño, Argelia; Charles, Marie-Aline; Cocco, Emmanuelle; Den Hond, Elly; Dewolf, Marie-Christine; Esteban-Lopez, Marta; Gilles, Liese; Govarts, Eva; Guignard, Cedric; Gutleb, Arno C; Hartmann, Christina; Kold Jensen, Tina; Koppen, Gudrun; Kosjek, Tina; Lambrechts, Nathalie; McEachan, Rosemary; Sakhi, Amrit K; Snoj Tratnik, Janja; Uhl, Maria; Urquiza, Jose; Vafeiadi, Marina; Van Nieuwenhuyse, An; Vrijheid, Martine; Weber, Till; Zaros, Cécile; Tarroja-Aulina, Elena; Knudsen, Lisbeth E; Covaci, Adrian; Barouki, Robert; Kolossa-Gehring, Marike; Schoeters, Greet; Denys, Sebastien; Fillol, Clémence; Rambaud, Loïc; Unión Europea. Comisión Europea. H2020; Wellcome Trust; Medical Research Council (Reino Unido); Economic and Social Research Council (Reino Unido); British Heart Foundation; NIHR - Collaboration for Leadership in Applied Health Research and Care Yorkshire and Humber; Unión Europea. Comisión Europea. 7 Programa Marco; Department of Environment and Health (Bélgica); Instituto de Salud Carlos III; Ministerio de Agricultura, Alimentación y Medio Ambiente (España); Slovenian Research Agency; Luxembourg Institute of Science and Technology; Danish Ministry of Environment and Food; Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (Alemania); Ministère de la Santé (Francia); French National Agency of Research (Francia); Government of Catalonia (España); Ministry of Higher Education and Research (Francia); Federal Ministry of Agriculture, Forestry, Environment and Water Management (Austria); Austrian Federal Ministry of Health (Austria); Environment and Health Fund (Israel); Environment Agency Austria
Background: Bisphenol A (BPA; or 4,4'-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. Objective: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18-73 years (n = 4,226) and its determinants. Methods: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. Results: Total BPA was quantified in 85-100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA's BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. Conclusion: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.
Enhanced Risk Assessment of Transformation Products through Chemical Similarity Analysis
(ACS Publications, 2024-04-17) Löffler, Paul; Lai, Adelene; Henschel, Henning; Spilsbury, Francis; Deviller, Genevieve; Tarazona, Jose; Yin Lai, Foon; Swedish Research Council
Applicability of Food Monitoring Data for Assessing Relative Exposure Contributions of Pyrethroids in Retrospective Human Biomonitoring Risk Estimations
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) De Alba-González, Mercedes; González-Caballero, MCarmen; Tarazona, Jose; Unión Europea. Comisión Europea. Horizonte Europa
The use of pyrethroids is very broad and shows increasing trends. Human biomonitoring studies represent the best approach for realistic risk estimations, but their interpretation requires a tiered approach. A previous HBM4EU study indicated levels in European children groups just around the threshold for concern, requiring further refinement. The main difficulty is that several pyrethroids with different toxicity potencies generate the same urinary metabolites. As diet is the main pyrethroid source for the general population, EU food monitoring data reported by EFSA have been used to estimate the relative contribution of each pyrethroid. The main contributors were cypermethrin for DCCA and 3-PBA and lambda-cyhalothrin for CFMP. Urinary levels predicted from food concentration according to the EFSA diets were mostly within the range of measured levels, except 3-PBA and CFMP levels in children, both below measured levels. The predicted lower levels for 3-PBA can be explained by the very low Fue value, initially proposed as conservative, but that seems to be unrealistic. The discrepancies for CFMP are mostly for the highest percentiles and require further assessments. The refined assessments included the revision of the previously proposed human biomonitoring guidance values for the general population, HBM-GV Gen Pop, following recent toxicological reevaluations, and the estimation of hazard quotients (HQs) for each individual pyrethroid and for the combined exposure to all pyrethroids. All HQs were below 1, indicating no immediate concern, but attention is required, particularly for children, with HQs in the range of 0.2-0.3 for the highly exposed group. The application of probabilistic methods offers assessments at the population level, addressing the variability in exposure and risk and providing relevant information for Public Health impact assessments and risk management prioritization.
A chemically functionalized glass support for gold and silver metallic nanoparticle analysis with LIBS
(Royal Society of Chemistry (RSC), 2024) Cárdenas-Escudero, Jafet; Gardette, V; Villalonga, A; Sánchez, A; Villalonga, R; Motto-Ros, V; Galan-Madruga, David; Cáceres, Jorge O; Ministerio de Economía y Competitividad (España); Complutense University of Madrid (España); Comunidad de Madrid (España); Ministerio de Ciencia e Innovación (España)
This work has focused on the development of a new analytical alternative based on the laser-induced breakdown spectroscopy (LIBS) technique for the fast, reliable, and economical determination of the gold and silver nanoparticle content in a low linear concentration range between 2.9 and 0.058 μg mL−1 and 2.9–0.116 μg mL−1, respectively, without requiring complicated sample pretreatment procedures or advanced separation techniques. Metallic nanoparticles are currently essential materials for the development of new technologies in different scientific and technical areas. However, numerous studies have pointed out these nanomaterials' toxic and polluting potential and the various health implications for humans, animals, and the ecosystem. The current reality reflects the lack of analytical techniques with low economic, environmental, and health impacts and the capacity to quantify the total metallic nanoparticle content. For this purpose, a novel and simple method for the selective capture of gold and silver nanoparticles, consisting of a chemically functionalized glass surface, has been custom-developed for subsequent analysis with LIBS. The results show that the proposed method, employing a functionalized sample glass support, presents a suitable analytical performance characterized by increased sensitivity, specifically 4.7% and 329.2% for Au-NPs and Ag-NPs, and proportionally decreased error in the slope and intercept of the calibration curves, 68% for Au-NPs and 87% for Ag-NPs, respectively.
Exposure assessment of the European adult population to deoxynivalenol - Results from the HBM4EU Aligned Studies.
(Elsevier, 2024-12) Namorado, Sónia; Martins, Carla; Ogura, Joana; Assunção, Ricardo; Vasco, Elsa; Appenzeller, Brice; Halldórsson, Thórhallur Ingi; Janasik, Beata; Kolossa-Gehring, Marike; Van Nieuwenhuyse, An; Ólafsdóttir, Kristin; Rambaud, Loïc; Riou, Margaux; Silva, Susana; Wasowicz, Wojciech; Weber, Till; Esteban-Lopez, Marta; Castaño, Argelia; Gilles, Liese; Rodriguez Martin, Laura; Govarts, Eva; Schoeters, Greet; Viegas, Susana; Silva, Maria João; Alvito, Paula; Unión Europea. Comisión Europea. H2020; Fundação para a Ciência e Tecnologia (Portugal)
Mycotoxins are natural toxins produced by fungi that may cause adverse health effects thus constituting a public health concern. Deoxynivalenol (DON), a mycotoxin affecting the immune system and causing intestinal disorders, was selected as a priority under the European Human Biomonitoring Initiative (HBM4EU). Urinary total DON levels (tDON) of 1270 participants from six countries were used to characterize the internal exposure of the adult European population and identify the most relevant determinants of exposure. tDON concentrations' P50 and P95 were in the range of 0.41-10.16 µg/L (0.39-9.05 µg/g crt) and 3.25-46.58 µg/L (2.12-33.50 µg/g crt) respectively. Higher tDON levels were observed for (i) male participants from France and Germany, (ii) samples collected in spring and summer, (iii) participants with a lower educational level, (iv) participants living in rural areas, (v) individuals without a job in France and Luxembourg, while in Portugal higher exposure was observed in working individuals, (vi) individuals with higher consumption of cereals and bread. The proportion of individuals with exposure levels exceeding the HBM-GV of 23 µg/L was 12.3 %, ranging from 0.8 % to 20.7 % in the individual countries. This study on mycotoxins exposure has used post harmonized questionnaire data and validated analytical methodologies for analysis and covered countries representing the four geographical regions of Europe, having produced much needed knowledge on the exposure of the European adult population to deoxynivalenol.
Molecular effects of polystyrene nanoplastics toxicity in zebrafish embryos (Danio rerio)
(Elsevier, 2023-01) Martin-Folgar, Raquel; Torres-Ruiz, Mónica; De Alba-González, Mercedes; Cañas Portilla, Ana Isabel; González-Caballero, MCarmen; Morales, Mónica; Instituto de Salud Carlos III; National University of Distance Education (España)
Plastics pose a health hazard to living beings and the environment. Plastic degradation produces nano-sized plastic particles (NPs) that end up in terrestrial and aquatic ecosystems, including oceans, rivers, and lakes. Their presence in air, drinking water, sediments, food, and personal care products leads to a variety of exposure routes for living beings, including humans. The toxicity mechanisms of these nanomaterials (NMs) in living organisms and ecosystems are currently unknown, making it a priority to understand their effects at the molecular and cellular levels. The zebrafish (Zf) (Danio rerio) is a model organism which has a high homology with humans and has been widely used to assess the hazard of different xenobiotics. In this study, the expression changes of different genes in 120 hpf Zf embryos (Zfe) after exposure to polystyrene (PS) NPs (30 nm) at concentrations of 0.1, 0.5 and 3 ppm were investigated. The results showed that the gene encoding heat shock protein (hsp70) was down-regulated in a dose-dependent manner. The genes encoding superoxide dismutase (SOD 1 and SOD 2), apoptotic genes (cas 1 and cas 8) and interleukin 1-β (il1β) were activated at the concentration of 3 ppm PS NP, while the anti-apoptotic gene Bcl2α was inhibited at 0.5 and 3 ppm. In addition, the neurotransmitter-related gene Acetyl-Cholinesterase (ache) was significantly inhibited and the DNA repair genes (gadd45α and rad51) were also down-regulated. In contrast, the mitochondrial metabolism-related gene cox1 did not alter its expression in any of the treatments. Most of the changes in gene expression occurred at the highest concentration of NPs. Overall, the results indicated that NPs generated cellular stress that caused certain alterations in normal gene expression (oxidative stress, apoptotic and inflammatory processes, neurotoxicity and anti-apoptotic proteins), but did not cause any mortality after 120 hpf exposure at the three concentrations assayed. These results highlight the need for further studies investigating the effects, at the molecular level, of these materials in humans and other living organisms.
Toxicity of nanoplastics for zebrafish embryos, what we know and where to go next
(Elsevier, 2021-11-25) Torres-Ruiz, Mónica; De la Vieja, Antonio; De Alba-González, Mercedes; Esteban-Lopez, Marta; Castaño, Argelia; Cañas Portilla, Ana Isabel; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Nanoplastics (NP) are an emerging threat to human health and there is a need to understand their toxicity. Zebrafish (ZF) is extensively used as a toxicology model due to its power to com-bine genetic, cellular, and whole organism endpoints. The present review integrates results regarding polystyrene NP effects on ZF embryo development. Study design was evaluated against NP effects. NP size, concentration, and exposure time did not affect organism responses (mortality, development, heart rate, locomotion) or cellular responses (gene expression, enzymes, metabolites). However, NP accumulation depended on size. Smaller NP can reach internal organs (brain, eyes, liver, pancreas, heart) but larger (>200 nm) accumulate mainly in gut, gills and skin. Locomotion and heart rate were commonly affected with hypoactivity and bradycardia being more prevalent. Effects on genetic/enzymatic/metabolic pathways were thoroughly analyzed. Immunity genes were generally upregulated whereas oxidative stress response genes varied. Central nervous system genes and visual related genes were generally downregulated. Results of genetic and enzymatic analyses coincided only for some genes/enzyme pairs. Reviewed studies provide a basis for understanding NP toxicity but results are hard to integrate. We propose key recommendations and future directions with regard to experimental design that may allow greater comparability across future studies.

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