Lung-deposited surface area concentration measurements in selected occupational and non-occupational environments

AbstractPrevious experimental and epidemiologic studies suggested that exposure to ultrafine particles (UFP) may result in adverse health effects. Metrics such as the number-concentration and especially the surface-area or lung-deposited surface area (LDSA) appear to be appropriate metrics of dose for predicting pulmonary inflammation of insoluble and poorly soluble ultrafine particles. Currently not much data including LDSA concentrations is available. The aim of this study was therefore to measure LDSA concentrations in a variety of occupational and non-occupational environments as well as in chamber tests. To this end, novel handheld online-monitors were deployed and evaluated for their suitability to be used in a variety of micro-environments and under different conditions. Chamber emissions tests included incense and candle burning, 3D printing and cigarette/e-cigarette smoking. The LDSA concentration was measured in occupational environments such as a canteen kitchen, a welding workshop and in a car. Measurements were also conducted in a private house with a wood-burning stove and with ongoing parallel cooking activities. Depending on the type of micro-environment, the ongoing activities or the material investigated in the chamber-tests, large differences were observed in terms of measured LDSA concentrations, some exceeding up to 1000 times that of the baseline concentration detected before activities initiated. In some of the investigated environments LDSA concentrations were measured for the first time. The data might therefore serve as reference for future studies. The handheld instrument used to measure this data worked well both for stationary measurements as well as for personal monitoring and proved to be an alternative to bulkier benchtop instruments

Desarrollo, evaluación y caracterización de Fases Reactivas, sensibles a diferentes analitos y su empleo en sensores ópticos en flujo

El objeto fundamental de la presente memoria se ha centrado en la evaluación de diferentes "terminales sensibles" a los analitos hierro y aluminio con el fin de seleccionar los mas adecuados para el desarrollo de sensores ópticos en flujo, de fluorescencia y de reflectancia. En todos los sensores desarrollados se ha seguido la misma sistemática de trabajo: construcción de la fase sensible al analito a determinar (elección del reactivo, soporte y proceso de inmovilización); diseño y optimización del sistema de medida; caracterización de la fase reactiva y aplicación a muestras reales. Se ha desarrollado un sensor basado en medidas de reflectancia para la determinación de fe(III) y al(III) que utiliza como fase reactiva cromazurol s inmovilizado en distintos soportes. El reactivo pioverdina, sideroforo fluorescente de origen natural que presenta una alta selectividad para el ion férrico, inmovilizado en diversos soportes inertes ha constituido el terminal sensible de dos sensores, caracterizados, tanto en continuo como en fia, para la determinación de hierro. Se ha cuantificado este analito en aguas de distintos orígenes y en suero humano mediante los métodos propuestos

Characterisation of mainstream and passive vapours emitted by selected electronic cigarettes

AbstractElectronic cigarettes have achieved growing popularity since their introduction onto the European market. They are promoted by manufacturers as healthier alternatives to tobacco cigarettes, however debate among scientists and public health experts about their possible impact on health and indoor air quality means further research into the product is required to ensure decisions of policymakers, health care providers and consumers are based on sound science. This study investigated and characterised the impact of ‘vaping’ (using electronic cigarettes) on indoor environments under controlled conditions using a 30m3 emission chamber. The study determined the composition of e-cigarette mainstream vapour in terms of propylene glycol, glycerol, carbonyls and nicotine emissions using a smoking machine with adapted smoking parameters. Two different base recipes for refill liquids, with three different amounts of nicotine each, were tested using two models of e-cigarettes. Refill liquids were analysed on their content of propylene glycol, glycerol, nicotine and qualitatively on their principal flavourings. Possible health effects of e-cigarette use are not discussed in this work. Electronic cigarettes tested in this study proved to be sources for propylene glycol, glycerol, nicotine, carbonyls and aerosol particulates. The extent of exposure differs significantly for active and passive ‘vapers’ (users of electronic cigarettes). Extrapolating from the average amounts of propylene glycol and glycerol condensed on the smoking machine filter pad to the resulting lung-concentration, estimated lung concentrations of 160 and 220mgm−3 for propylene glycol and glycerol were obtained, respectively. Vaping refill liquids with nicotine concentrations of 9mgmL−1 led to vapour condensate nicotine amounts comparable to those of low-nicotine regular cigarettes (0.15–0.2mg). In chamber studies, peak concentrations of 2200μgm−3 for propylene glycol, 136μgm−3 for glycerol and 0.6μgm−3 for nicotine were reached. Carbonyls were not detected above the detection limits in chamber studies. Particles in the size range of 20nm to 300nm constantly increased during vaping activity and reached final peak concentrations of 7×106particlesL−1. Moreover, the tested products showed design flaws such as leakages from the cartridge reservoirs. Possible long term effects of e-cigarettes on health are not yet known. E-cigarettes, the impact of vaping on health and the composition of refill liquids require therefore further research into the product characteristics. The consumers would benefit from harmonised quality and safety improvements of e-cigarettes and refill liquids

Development of a HPLC-UV method for the simultaneous determination of intracellular glutathione species in human cells

In the present work, an HPLC-UV method was set-up to allow the simultaneous quantification of the reduced-GSH, oxidised-GSSG and nitroso-GSNO glutathione species. Chromatographic separation was achieved on YMC ODS-A C18 column (150 × 4.6 mm, 5 μm), coupled to a Guard-c precolumn (YMC-Pack, 10 × 1-4,0 mm). The eluted compounds were detected at 215 nm by UV-detector, by keeping the column oven at room temperature while the auto-sampler temperature was maintained at 4°C. A fractional factorial design has been applied for the optimization of the mobile phase resulting in baseline separated peaks within 6 minutes. In-house validation was evaluated by linearity, limits of detection (LODs), limits of quantification (LOQs), reproducibility, repeatability and recovery. The detection and quantification limits obtained for standard solutions were below 0.2 μM and 0.6 μM, respectively (RSD values below 2%). The developed method was applied to the measurement of GSH, GSSG and GSNO in human pulmonary cells (A549) exposed to limonene, limonene oxide solubilized into the culture medium and to NO2 as gas phase. Results show an increase in GSH levels, without significant changes in GSSG, when cells were exposed to limonene oxide, while cells exposed to NO2 resulted in a significant increase of GSNO amount. Detection limits were of 1 μM for the glutathione species measured in A549 cells, with RSD values below 2.5%. In conclusion, the present HPLC-UV method can be readily used to measure in a rapid, simultaneous and accurate way the status of GSH, GSSG and GSNO in human cells, their simultaneous quantification helping to better predict the potential impact of chemicals on human health.JRC.I.1-Chemical Assessment and Testin

Multimethod approach for the detection and characterisation of food-grade synthetic amorphous silica nanoparticles

AbstractSynthetic amorphous silica (SAS) has been used as food additive under the code E551 for decades and the agrifood sector is considered a main exposure vector for humans and environment. However, there is still a lack of detailed methodologies for the determination of SAS’ particle size and concentration. This work presents the detection and characterization of NPs in eleven different food-grade SAS samples, following a reasoned and detailed sequential methodology. Dynamic Light Scattering (DLS), Multiangle Light Scattering (MALS), Asymmetric Flow-Field Flow Fractionation (AF4), Inductively Coupled Plasma Mass Spectrometry (ICPMS) and Transmission Electron Microscopy (TEM) were used. The suitability and limitations, information derived from each type of analytical technique and implications related to current EC Regulation 1169/2011 on the provision of food information to consumers are deeply discussed. In general the z-average, AF4 hydrodynamic diameters and root mean square (rms) radii measured were in good agreement. AF4-ICPMS coupling and pre channel calibration with silica NPs standards allowed the reliable detection of NPs below 100nm for ten of eleven samples (AF4 diameters between 20.6 and 39.8nm) and to quantify the mass concentration in seven different samples (at mgL−1 concentration level). TEM characterisation included the determination of the minimum detectable size and subsequent measurement of the equivalent circle diameter (ECD) of primary particles and small aggregates, which were between 10.3 and 20.3nm. Because of the dynamic size application range is limited by the minimum detectable size, all the techniques in this work can be used only as positive tests

3D Bioprinting of Human Adipose-Derived Stem Cells and Their Tenogenic Differentiation in Clinical-Grade Medium

Defining the best combination of cells and biomaterials is a key challenge for the development of tendon tissue engineering (TE) strategies. Adipose-derived stem cells (ASCs) are ideal candidates for this purpose. In addition, controlled cell-based products adherent to good manufacturing practice (GMP) are required for their clinical scale-up. With this aim, in this study, ASC 3D bioprinting and GMP-compliant tenogenic differentiation were investigated. In detail, primary human ASCs were embedded within a nanofibrillar-cellulose/alginate bioink and 3D-bioprinted into multi-layered square-grid matrices. Bioink viscoelastic properties and scaffold ultrastructural morphology were analyzed by rheology and scanning electron microscopy (SEM). The optimal cell concentration for printing among 3, 6 and 9 × 106 ASC/mL was evaluated in terms of cell viability. ASC morphology was characterized by SEM and F-actin immunostaining. Tenogenic differentiation ability was then evaluated in terms of cell viability, morphology and expression of scleraxis and collagen type III by biochemical induction using BMP-12, TGF-β3, CTGF and ascorbic acid supplementation (TENO). Pro-inflammatory cytokine release was also assessed. Bioprinted ASCs showed high viability and survival and exhibited a tenocyte-like phenotype after biochemical induction, with no inflammatory response to the bioink. In conclusion, we report a first proof of concept for the clinical scale-up of ASC 3D bioprinting for tendon TE

European Parliament Pilot Project on Exposure to Indoor air Chemicals and Possible Health Risks

This report outlines the results of the 2-year pilot project on indoor air quality and potential health effects executed by the Joint Research Centre and funded by the European Parliament via the Directorate-General Health and Consumer Protection. It had four distinct objectives as follows: 1) to identify and quantify the main air pollutants present in public buildings, including indoor environments where children frequently stay, like schools and kindergartens, 2) to identify the main sources of these pollutants, applying source apportionment analyses, 3) to estimate people¿s exposure to these pollutants while working and/or living in these areas and combined with micro-environmental activity patterns during the day, 4) to evaluate possible health risks due to (chronic) exposure to air pollutants, in particular, for children. The results indicate that indoor air pollution concentrations are consistently higher than the respective outdoor ones for the chemical families this study focused on. Differences attributable to variation in consumer behaviour, climate and type of building materials used, have been identified in the indoor:outdoor ratio of primary pollutants across Europe. These differences account for small variance in the corresponding health risk to the local population across the EU.JRC.I.5-Physical and chemical exposure

Migration of Polycyclic Aromatic Hydrocarbons (PAHs) from plastic and rubber articles

Polycyclic Aromatic Hydrocarbons (PAHs) constitute a large group of chemically related substances many of which are known carcinogens. To minimise human exposure there are already several pieces of EU legislation which limit their presence in certain food products, as well as in water and ambient air. Under the REACH regulation (EC 1907/2006 Annex XVII, Entry 50), eight priority PAHs have for some time been restricted in extender oils used in tyres. Although not added deliberately to consumer products, PAHs can still be present as impurities. An amendment of the above mentioned legislation (Regulation EU 1272/2013) establishes content limits for the eight PAHs of 0.5 mg kg-1 for plastic and rubber components of toys/childcare articles, and 1 mg kg-1 for all other consumer articles, in direct and prolonged, or short-term repetitive, contact with the skin or oral cavity. In May 2016 DG JRC and DG GROW signed an Administrative Arrangement (AA 34003) known as the STANPAHs project. The main objective of this contract was for the JRC to provide scientific support in the implementation and potential amendment of the restriction on polycyclic aromatic hydrocarbons, in particular concerning paragraphs 5 and 6 of entry 50 of Annex XVII to the REACH legislation. The main objectives of the project were: a) to gain a better understanding of the migration behaviour of certain PAHs in plastic and rubber components of articles, and b) to develop a reliable methodology to determine PAH migration from these matrices, under conditions simulating, to the best possible extent, dermal contact (including the oral cavity). This report presents the outcomes of the experimental studies carried out at JRC and the achievements towards fulfilling these objectives. A set of manufactured polymeric plastic and rubber matrices, to be used as test materials in the project, has been chosen based on criteria such as their frequency of use in articles within the scope of the restriction and the likelihood of the presence of high PAH contents (e.g. due to their content in carbon black or extender oils). Various grades and types of ingredients known to be PAH sources were used in the formulation of the manufactured ad-hoc materials. The test materials included low density polyethylene (LDPE), polystyrene (PS) and polyvinyl chloride (PVC) as plastic matrices, and ethylene-propylene diene monomer (EPDM), natural rubber-butadiene rubber (NR-BR) and silicone as rubber matrices. Moreover, recycled granules (coated and uncoated) originating from end-of-life tyres produced before and after 2010 as well as rubber tiles made of the recycled coated granules were also made available for this study. The content of each of the eight restricted PAHs was measured by using a method developed in-house based on Randall hot extraction, purification by Solid Phase Extraction based on Molecular Imprinted Polymers, and Gas Chromatography Mass Spectrometry determination. A number of experimental studies were undertaken to generate data and information to improve the knowledge on migration of the target PAHs. Migration parameters operated in the STANPAHs project to estimate migration rates were as follows: dynamic mode at 40°C for 24 hours using a variety of migration media including artificial aqueous simulants, modified biosimulants formulations with lipidic content such as skin surface film liquid (SSFL), and 20% ethanol in water. According to scientific literature the use of 20% ethanol as the migration medium proved to correlate well with human skin absorption. Using these conditions, migration of the target PAHs into artificial sweat (EN1811) and artificial saliva (DIN53160-1) was not detected in any of the materials studied. Moreover none of the plastic polymeric materials led to detectable release of the target PAHs in any of the migration media used in this study (i.e. artificial sweat and saliva, skin surface film liquid (SSFL), and 20% ethanol solution). Similarly the tests with silicone materials did not result in detectable migration. Only the rubber matrices containing Distillate Aromatic Extract (DAE) as extender oil showed detectable migration when using 20% ethanol as the migration solution. In addition, the release of PAHs from coated recycled rubber granules was lower than from the uncoated granules suggesting that the coating acts as a barrier to chemical migration. According to industrial partners DAE is not used by European industries for manufacturing of parts of articles intended for skin contact. The materials containing DAE, although not representative for marketed products, have been made available to facilitate migration testing method development. The migration test method using 20% ethanol has been validated in-house and shows good method performance allowing the determination of PAH at trace level. Furthermore it has been considered for an initial inter-laboratory comparison study (ILC) aiming to investigate method applicability and transferability in a variety of laboratories. The within-laboratory precision, expressed as the relative standard deviation for repeatability (RSDr), and the between-laboratory precision, expressed as the relative standard deviation for reproducibility (RSDR) were assessed. In general the RSDR ranged from 28 to 113% and the RSDr from 7 to 23%. It is worth remembering that the level of PAH migration was very close to the quantification limit of the method and therefore this variability can be expected. Similar values have been reported in a recent German study with the participation of 9 laboratories on the migration of PAHs from rubber materials in contact with aqueous ethanol. The fact that better values of RSDr and RSDR were obtained for chrysene and benzo(e)pyrene that had the highest concentrations in the final migration solutions and that the analysis of the control solution used in this exercise showed a good reproducibility (RSDR% <10%), shows the possibility to reduce the variability between laboratories with a revised operating procedure in terms of injection volume and/or elution volume. In conclusion this report makes available new data and scientific information on the migration behaviour of certain PAHs from selected plastic and rubber polymeric matrices, in support of the European Commission's legal obligation to review the PAHs restriction under REACH. Standard operating procedures for quantification of the content of each of the eight restricted PAHs as well as their migration into 20% ethanol have been developed. Moreover the information gathered in STANPAHs (e.g. literature search), the ad-hoc manufactured materials still available, as well as the JRC in-house analysis method for PAH content could be of great benefit to accelerate the work towards standardisation of PAH content analysis in consumer products that has been recently undertaken by the European Standardisation Committee following a request by DG GROW.JRC.F.2-Consumer Products Safet

Tutorial action in the EHEA at the Faculty of Pharmacy of US: 4 years of experience of a student mentoring program

La Facultad de Farmacia de la Universidad de Sevilla (US) tiene en marcha un Programa de Alumnos Tutores desde 2006/07 con el objetivo de que alumnos de cursos superiores (AATT) tutelen a alumnos de nuevo ingreso (1x3). Pretende generar una actitud responsable en los AATT y favorecerles el desarrollo de habilidades sociales, objetivos cualitativos dentro de la educación universitaria que sirven como preparación previa a su inserción en el mundo laboral. La actividad es supervisada por Profesores Tutores (1x3) que analizan la evolución de ambos grupos de alumnos. Es una supervisión activa a través de distintas vías de acción para ayudar a la consecución de objetivos, tales como entrevistas periódicas, revisión de informes, acciones de apoyo como charlas sobre técnicas de estudio, coloquios sobre salidas laborales, exposiciones de las experiencias personales de algunos alumnos recientemente egresados, gestión estratégica de búsqueda de empleo, elaboración de portafolios,… Con respecto a la evolución del programa, el número de profesores ha crecido moderadamente llegando a una situación estable, mientras que el número de alumnos, tanto tutores como tutelados, ha crecido en un ritmo constante acorde a las restricciones indicadas. Los resultados son muy positivos, entendiéndose que el proyecto se enmarca en un contexto más cualitativo que cuantitativo y que el principal objetivo es el robustecimiento de la experiencia y asentar una dinámica de apoyo hacia los alumnos de nuevo ingreso y de planificación de tareas, tutela y responsabilidad en general de los alumnos tutores.The Faculty of Pharmacy of the University of Seville (US) has developed a Student Mentoring Program (from 2006/07 - present). The main objective of this project is that senior students act as Mentor Students for students at their first year in the University (1x3). It aims to generate a responsible attitude in mentor students and to promote the development of social skills, qualitative goals within higher education that serve as preparation prior to their integration into the world of work. This activity is supervised by Mentor Professors (1x3) that analyze the evolution of both groups of students. It is an active monitoring through various actions such as regular interviews, review of reports, support operations such as lectures on study skills, seminars on job opportunities, statements of personal experiences of some recently graduated students, strategic management job search, portfolio development... With regard to the development of the program, the number of Mentor Professors has grown moderately, reaching a stable condition, while the number of students, both tutor and supervised, has grown steadily in line with the restrictions indicated. The results are very positive, considering the more qualitative than quantitative character of the project and that the main objectives are the strengthening of the experience and the establishment of a dynamic support to the new students and scheduling and general responsibility for mentor students

Cybersecurity, our digital anchor: A European perspective

The Report ‘Cybersecurity – Our Digital Anchor’ brings together research from different disciplinary fields of the Joint Research Centre (JRC), the European Commission's science and knowledge service. It provides multidimensional insights into the growth of cybersecurity over the last 40 years, identifying weaknesses in the current digital evolution and their impacts on European citizens and industry. The report also sets out the elements that potentially could be used to shape a brighter and more secure future for Europe’s digital society, taking into account the new cybersecurity challenges triggered by the COVID-19 crisis. According to some projections, cybercrime will cost the world EUR 5.5 trillion by the end of 2020, up from EUR 2.7 trillion in 2015, due in part to the exploitation of the COVID-19 pandemic by cyber criminals. This figure represents the largest transfer of economic wealth in history, more profitable than the global trade in all major illegal drugs combined, putting at risk incentives for innovation and investment. Furthermore, cyber threats have moved beyond cybercrime and have become a matter of national security. The report addresses relevant issues, including: - Critical infrastructures: today, digital technologies are at the heart of all our critical infrastructures. Hence, their cybersecurity is already – and will become increasingly – a matter of critical infrastructure protection (see the cases of Estonia and Ukraine). - Magnitude of impact: the number of citizens, organisations and businesses impacted simultaneously by a single attack can be huge. - Complexity and duration of attacks: attacks are becoming more and more complex, demonstrating attackers’ enhanced planning capabilities. Moreover, attacks are often only detected post-mortem . - Computational power: the spread of malware also able to infect mobile and Internet of Things (IoT) devices (as in the case of Mirai botnet), hugely increases the distributed computational power of the attacks (especially in the case of denial of services (DoS)). The same phenomenon makes the eradication of an attack much more difficult. - Societal aspects: cyber threats can have a potentially massive impact on society, up to the point of undermining the trust citizens have in digital services. As such services are intertwined with our daily life, any successful cybersecurity strategy must take into consideration the human and, more generally, societal aspects. This report shows how the evolution of cybersecurity has always been determined by a type of cause-and-effect trend: the rise in new digital technologies followed by the discovery of new vulnerabilities, for which new cybersecurity measures must be identified. However, the magnitude and impacts of today's cyber attacks are now so critical that the digital society must prepare itself before attacks happen. Cybersecurity resilience along with measures to deter attacks and new ways to avoid software vulnerabilities should be enhanced, developed and supported. The ‘leitmotiv’ of this report is the need for a paradigm shift in the way cybersecurity is designed and deployed, to make it more proactive and better linked to societal needs. Given that data flows and information are the lifeblood of today’s digital society, cybersecurity is essential for ensuring that digital services work safely and securely while simultaneously guaranteeing citizens’ privacy and data protection. Thus, cybersecurity is evolving from a technological ‘option’ to a societal must. From big data to hyperconnectivity, from edge computing to the IoT, to artificial intelligence (AI), quantum computing and blockchain technologies, the ‘nitty-gritty’ details of cybersecurity implementation will always remain field-specific due to specific sectoral constraints. This brings with it inherent risks of a digital society with heterogeneous and inconsistent levels of security. To counteract this, we argue for a coherent, cross-sectoral and cross-societal cybersecurity strategy which can be implemented across all layers of European society. This strategy should cover not only the technological aspects but also the societal dimensions of ‘behaving in a cyber-secure way’. Consequently, the report concludes by presenting a series of possible actions instrumental to building a European digital society secure by design.JRC.E.3-Cyber and Digital Citizens' Securit