bluuebunny/crossref_metadata_2025_split huggingface dataset:
116 A Performance Testing Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugs
Authors: Pengelly Ian , Wilkinson Alan 
Published: May 2023

Abstract
Cytotoxic and other hazardous drugs, whilst potentially therapeutic to patients, pose an occupational exposure hazard to healthcare workers during compounding and administration. However, occupational exposure to these drug compounds can be reduced with the use of closed system transfer devices (CSTDs) designed to prevent the escape of aerosol, liquid or vapour from a hazardous drug vial. In 2015 NIOSH developed a test procedure to assess the containment performance of CSTDs using an isopropanol-water challenge agent and infra-red detection. However, this protocol could not be used to assess devices using air filtration technology. HSE and BSTL therefore developed a modified procedure, using less volatile challenge agents and measurement using thermal desorption (TD) and gas chromatography-mass spectrometry (GC-MS), which could be used to assess all CSTD types. Unlike the NIOSH procedure this approach does not give a ‘real-time’ result but shows significantly greater sensitivity with the challenge agents used; typically being able to detect an airborne concentration of less than 1 part per billion (ppb). Testing carried out using a solution of 2-phenoxyethanol as the challenge agent showed no evidence of release with three of the four CSTDs tested; two barrier devices and one using air filtration. The tests also showed limits of detection to be dependent not only on the analytical procedure but on the effectiveness of the cleaning regime used to decontaminate the exposure chamber between tests.
123 Characterisation and Modification of the Porous Metal Foams Used for the En 15051-2 Dustiness Rotating Drum Test
Authors: Bard Delphine , Hunwin Graeme , Thorpe Andrew , Dewberry Kirsty , Roberts Paul , Burdett Garry 
Published: May 2023

Abstract
Handling of hazardous materials in occupational settings can lead to worker exposure by inhalation. Dustiness testing, such as the EN 15051-2 rotating drum tester, provides suppliers and users of bulk materials with information on the potential for dust emission from hazardous substances when handled or processed in the workplace. This tester agitates powder samples in a rotating drum and the resulting dust is collected and sized by drawing it through two reticulated metal foams. Two approaches were used to evaluate the performance of the metal foams. Firstly, the performance of the metal foams was measured in a calm air chamber using a polydisperse aerosol of glass particles and assessed against the EN 481 respirable convention. Secondly, the performance of the metal foam for the respirable fraction was compared using the rotating drum dustiness test, with that of a cyclone set-up, using four polydisperse glass powders of different size distribution and dustiness potential. In general, for the respirable fraction, the tests demonstrated a conservative oversampling by the current EN 15051-2 metal foam set-up in comparison with the EN 481 convention. This study also showed the importance of sealing the circumference of the metal foams when testing highly dusty powders. A direct comparison of the respirable dustiness fraction measured by the current EN 15051-2 metal foams set-up and by a cyclone set-up, showed broad agreement. However, the cyclone gave lower values except where foam clogging occurred. The research also highlighted suggested improvements to the EN 15051-2 standard.
© Crown Copyright (2022)
132 Evaluation of the Effectiveness of a New Technical Solution to Reduce Dust Emission from Road Planers
Authors: Rousset Davy , Lechene Sullivan , Bemer Denis , Bonthoux Francis , Matera Virginie 
Published: May 2023

Abstract
A planer equipped with a rotating cutting drum is used to remove about ten cm thick of road surfaces. This process generates dust likely to contain crystalline silica. The machine operator and people around may be particularly exposed. It is therefore essential to promote effective preventive solutions, in particular from dust collection and filtration systems, to reduce dust exposure. Tests were realized to evaluate the performance of technical devices designed to capture and filter dust emitted by road planers. The measurements were carried out on a road planer equipped with an air collection device located next to the milling drum, supplemented by an electrostatic separator to trap collected dust. The dust collection efficiency of the venting system was determined by gas tracing. The efficiency of the electrostatic separator was both evaluated in laboratory conditions (static machine) from a reference dust generated upstream of the system, and in the field during road surface planing. The tests conducted on the planer showed the effectiveness of the dust collection and filtration devices implanted on the machine and tested both in static and in the field. The capture efficiency determined by gas tracing is about 90 % and the separation efficiency of the electrostatic precipitator, determined on the static machine from test dust, is respectively 60 and 90% at aerodynamic diameters 1 and 4 μm. The average separation efficiency obtained from the measurements with the machine in real operation is 91% for respirable dust and 95% for respirable crystalline silica.
159 Keynote: An Overview of Carbon Nanotube Carcinogenesis from Mouse Inhalation Data
Authors: Kanno Jun , Taquahashi Yuhji , Ishimaru Naozumi , Kitajima Satoshi 
Published: May 2023

Abstract
There were “miracle materials” at the time that were later banned. Most of them were “biopersistent” and had “mild acute toxicity but nasty chronic toxicity”. This toxicity gap had given time to allow for mass use before ban. Most carbon-based nanomaterials are taught to be biopersistent and therefore we investigated their chronic inhalation toxicity as a part of particulate matter toxicology. We developed a universal dispersion method and a small-scale cheap and easy inhalation system named “Taquann”. The first sample was Mitsui-7 multiwall carbon nanotube (MWCNT) donated by the company. Based on its size and shape, we referred to the asbestos and performed the intraperitoneal injection studies. Meanwhile, we started monitoring the inhaled mouse lung for the mechanism of lung fibrosis and carcinogenesis. The responses against inhaled particles were monitored in three studies (A) 2hr/day x 5days of inhalation (Mitsui-7) with monitoring at 0, 13w, 26w, 52w, (B) 2hr/day/week x 5weeks (Mitsui-7, TiO2 , MWCNT-N) at 0, 1w, 4w, 8, and (C) 6hr/day/4weeks x 104weeks (Mitsui-7) at 26w, 52w, 104w. There were responses common and different among rigid fiber, tangled fiber and non-fiber particles. Alveolar macrophages tend to phagocytize at its full capacity and relocate to a certain position in the lung, and/or die off, releasing the particles to be re-phagocytized. Type II cell proliferation and interstitial fibrosis may be related to the level of “frustrated phagocytosis” which may be maximized by rigid fibers. More detail including immune responses and lymphatics will be presented. (Health and Labour Science Research Grants).
1 (Nano)Particle Exposure, Acute Phase Response and Cardiovascular Disease
Authors: Vogel Ulla , Gutierrez Claudia T , Poulsen Sarah S , Danielsen Pernille , Hadrup Niels , Saber Anne T 
Published: May 2023

Abstract
Particle inhalation is linked to diseases including cancer, COPD, fibrosis and cardiovascular disease. We propose a biological mechanism-of-action for particle-induced cardiovascular disease causally linking particle exposure to induction of acute phase response, which in turn is a known risk factor for atherosclerosis and cardiovascular disease. Inhalation and pulmonary deposition of particles induce inflammation, which is proportional to the total surface area of the pulmonary-deposited particles. In mice, inflammation is accompanied by an acute phase response, which is long-lasting for insoluble particles. Acute phase protein Serum Amyloid A (SAA) is among the most differentially expressed genes in lung tissue following particle exposure. SAA is causally implicated in atherosclerosis and both overexpression and pulmonary dosing of SAA promote plaque formation in ApoE-/- mice. In mice, we show that both soluble and insoluble metal fume particles induce acute phase response but with different time-dependence. Neutrophil influx, pulmonary Saa expression and SAA blood levels are highly correlated in mice and may be used as biomarkers of each other. In humans, controlled exposure to metal oxides and combustion particles induces dose-dependent increases in blood levels of SAA and C-reactive protein. Blood levels of acute phase proteins SAA and C-reactive protein are risk factors for cardiovascular disease in prospective, epidemiological studies. Nanoparticles have a higher specific surface area than larger particles with similar chemical composition, and consequently, nanoparticles are more hazardous than larger particles of similar chemical composition in relation to cardiovascular disease. This underscores cardiovascular disease as a particle-induced occupational disease.
15 Biomonitoring for Respirable Crystalline Silica: Determination of Si-Containing Particles in Exhaled Breath Condensate Using Single Particle Inductively Coupled Mass Spectrometry
Authors: Morton Jackie , Leese Elizabeth 
Published: May 2023

Abstract
Biological monitoring is a useful way of determining overall exposures to chemical substances; however, in the case of respirable crystalline silica (RCS), this has not been possible in conventional biological matrices. Previous research at HSE has shown that it was possible to detect silicon-containing particles in exhaled breath condensate (EBC) samples using single particle inductively coupled mass spectrometry (spICPMS) in a small number of quarry workers, and at that time the method had a particle size detection limit of around 300 nm. In more recent work presented here we will describe the advances in the methodology and the results from exhaled breath condensate samples collected from a range of UK workers with potential RCS exposures. Control samples were also collected for comparison. Static air/bulk samples were also collected to allow the size distribution and concentration of RCS to be determined in each workplace. The analytical advances include moving to using an ICP tandem MS for better specificity with an improved sample introduction system. This has increased the size range detection of silicon-containing particles, allowing measurements in the size range of 100-2000 nm, in a one minute acquisition. We have also standardised the EBC sampling by collecting the same volume of exhaled air (50L) from each volunteer. This improved methodology offers a viable biomonitoring method for a range of workplaces and has the potential to inform information about the efficacy of respiratory protective equipment and control measures in the workplace, complementing occupational hygiene.
16 Biological Effects of Benzo-[A]-Pyrene and Cerium Nanoparticles on the Human Placental Barrier
Authors: Deval Gaëlle , Degrelle Séverine , Boland Sonja , Devineau Stéphanie , Vignaud Marie-Leone , Rogozarski Jasmina , Chissey Audrey , Mrozik Adrian , Borderie Didier , Fournier Thierry , Zerrad-Saadi Amal , Ferecatu Ioana 
Published: May 2023

Abstract
The human placenta is a transitory organ essential for fetal development, whose functions can be disrupted by xenobiotics in maternal blood. Benzo-[a]-pyrene (B[a]P) is a carcinogenic, mutagenic and reprotoxic pollutant as well as an endocrine disruptor that can be internalized in the human body by respiratory exposure. Cerium dioxide nanoparticles (CeO2 NP) have been introduced into our environment, mainly for their catalytic properties and share the same emission sources as B[a]P (cigarette smoke and diesel engine exhaust). The aim of our study is to determine the impact of these two atmospheric pollutants on the human placenta in concomitant exposure, in order to get closer to the environmental reality. Chorionic villi and villous cytotrophoblasts (VCT) from human placentas at term of pregnancy were exposed in vitro to the pollutants. The internalization of the pollutants was observed by confocal and Raman microscopy. Cytotoxicity was assessed using WST-1 test and extracellular LDH assay. Placental endocrine activity was assessed by ELISA. The signaling pathways impacted have been studied by Western Blot, RT-qPCR and IHC. CeO2 NP and B[a]P can be internalized within the chorionic villi. B[a]P alone or in co-exposure with CeO2 NP activate the metabolic pathway of the aryl hydrocarbon receptor (AhR), causing DNA damage. B[a]P also stabilizes the stress transcription factor p53 and its transcriptional target p21. Although these two pollutants do not cause major toxicity on term human trophoblasts after in vitro exposures, cellular stress markers are induced.
45 Behavior and Effect of Nanoparticles on Neutrophil Recruitment in the Pulmonary Microcirculation
Authors: Li Chenxi , Liu Qiongliang , Stoeger Tobias , Rehberg Markus 
Published: May 2023

Abstract
NP exposure is frequently associated with adverse cardiovascular effects. A small fraction of NP deposited in lung has been shown to penetrate into the blood circulation. However, the interactions and effects of NP in the pulmonary microcirculation under healthy and pathophysiologic conditions such as LPS-induced acute lung injury are largely unknown. To visualize and quantify NP dynamics and pulmonary vascular innate immune responses elicited by different surface-modified NPs in real time, we applied state-of-the-art intra-vital microscopy in the alveolar region of murine lungs. I.v. injected polyethylene-glycol-amine (aPEG)-QDs and carboxyl-QDs exhibited a half-life time of 30 and 6 mins in the microcirculation and did not permanently interact with vessel wall. Blood flow velocity was significantly decreased after aPEG-QDs application in healthy mice, but did not further decrease the reduced microcirculatory perfusion after LPS treatment. In healthy mice, aPEG-QDs elicited a significant increase in neutrophil number in alveolar micro-vessels from 30 min upon application compared to controls, whereas cQDs induced only a slight neutrophil increment. Accordingly, the crawling velocity of neutrophils in pulmonary micro-vessels was significantly reduced after aPEG-QDs application. No effect of QDs on neutrophil number and crawling was detected in the LPS group. Importantly, neutrophil recruitment by aPEG-QDs was diminished by prior i.v. application of anti-TNFa, anti-E-selectin and anti-LFA-1 blocking antibodies. Taken together our data suggest that aPEG-QDs induced microvascular inflammation involving TNFa secretion, expression of the vascular cell adhesion molecule E-selectin and neutrophil integrin LFA-1, whereas QDs application did not alter LPS-dependent microvascular inflammation.
60 Multimodal Imaging and Artificial Intelligence Unveil Hot-Spot Deposition, Bronchial/Alveolar Dose and Cellular Fate of Biopersistent Nanoparticles in the Lung
Authors: Yang Lin , Liu Qiongliang , Kumar Pramod , Sengupta Arunima , Farnoud Ali , Shen Ruolin , Trofimova Darya , Ziegler Sebastian , Kutschke David , Kreyling Wolfgang , Piraud Marie , Isensee Fabian , Burgstaller Gerald , Rehberg Markus , Stoeger Tobias , Schmid Otmar 
Published: May 2023

Abstract
Pulmonary delivery is not only of increasing importance to exploit local therapy for lung diseases like COVID-19, but also plays an essential role in interpreting health impact of inhaled hazardous (nano-)materials. Deciphering of biodistribution, biokinetics, and cell-mediated immunity of pulmonary delivered nanoparticles (NPs) remains insufficient. We applied state-of-the-art multimodal imaging and deep learning pipelines to elucidate the intricate deposition profiles and the fate of biopersistent NPs in the lung within cellular resolution. Spatially resolved delivery characteristics like inter- and intra-acinar distribution pattern and regional NP dosage were revealed by tissue-clearing light-sheet fluorescence microscopy for six common routes of pulmonary delivery, i.e., intranasal & oropharyngeal aspiration, intubated instillation, microsprayer application, ventilator-assisted & nose-only aerosol inhalation. Artificial intelligence-driven entire airway 3D segmentation (convolutional neural network) enabled accurate dosimetry of bronchial versus acinar/alveolar NP dose (B/A: 0.04 to 0.18 depending on delivery route) rather than the conventionally simplified 2D central-to-peripheral ratio (C/P: 1.32 to 3.79). Moreover, longitudinal 3D imaging revealed similar intra-acinar NP kinetics independent of delivery route. Inhaled NP relocation from the alveolar-epithelium to interstitium was traditionally claimed as the consequence of passive diffusion/transportation of NPs. This study, however, revealed that acinar NP transport can be attributed to the phagocytosis and migration of tissue-resident macrophages (TRMs) as evidenced by complementary analytical approaches (intravital microscopy, ex vivo 4D live-tissue microscopy, in situ immunofluorescence, ex vivo NP-lung interaction model, flow cytometry). Overall, this study elucidates holistic NP-lung delivery and biokinetics features and TRM immunity on the fate of biopersistent NPs.
73 Evaluating the Risks of Prolonged Exposure to Graphene Oxide on Healthy and Streptococcus Pneumoniae Infected 3D Reconstituted Human Lung Cultures
Authors: Buerki-Thurnherr Tina , Nigg Susanne , Albrich Werner , Kahlert Christian , Lozano Neus , Bussy Cyrill , Kostarelos Kostas , Wick Peter , Chortarea Savvina 
Published: May 2023

Abstract
The growing production of graphene oxide (GO) and GO-based products has led to an increased risk of human exposure and caused scientific and public concern about human health and safety. Even though human exposure to GO can occur via different pathways, the main exposure route for airborn GO is through the lungs, thus placing the respiratory tract at particular risk. Occupational exposure to GO might occur repeatedly over a prolonged period of time but insights on lung toxicity of long-term repeated GO administration is largely lacking. Moreover, there is a risk that GO co-exposure with prevalent lung pathogens (e.g. Streptococcus pneumoniae (SP)) could increase the susceptibility to lung infections. In this study, we aimed to investigate the impact of repeated and prolonged GO exposure in healthy and SP-infected lungs using well-characterized materials with distinct properties and reconstituted primary human bronchial epithelial cultures. Our results revealed that GO had no major toxicity effects on healthy airway epithelium even upon prolonged exposure, but alterations in inflammatory/immune signaling was apparent and showed a correlation with the lateral particle size. GO pre-exposure slightly altered the response of the airway epithelium towards subsequent SP infection as evidenced by a decreased mitochondrial activity, increased bacterial translocation and altered inflammatory/immune responses. Whole genome transcriptomic profiling is ongoing to gain insights in deregulated genes and pathways following chronic GO administration. Our findings on the health risks of GO inhalation in healthy and infected human lung is important to risk assessment and management of this promising material.
79 Combination of Screening and Higher tier Modelling Approaches for Estimating Inhalation Exposure During Spray Applications
Authors: Hahn Stefan , Nowak Norman , Schwarz Katharina , Schwarz Janine , Tischer Martin , Meyer Jessica , Koch Wolfgang 
Published: May 2023

Abstract
Sprays are used in workplace as well as in consumer environments. Although spraying has several advantages such as uniform distribution of substances on surfaces in a highly efficient manner it is often prone to high inhalation burden which has to be quantified for adequate risk assessments. There are occupational exposure models with different degree of complexity available that are applied for spray applications. In the presentation we report on an effort to create an overall model for estimating inhalation exposure caused by spray applications by re-analyzing, refining and integrating three already existing models into a 2-level tiered approach. The single models used in this context are a 1- and 2-box mass balance model (Tier 1), Spray Expo and a newly developed binary system model (Tier 2). The Tier 1 level models are used for an initial assessment generally designed to deliver conservative results. Only if product safety cannot be derived from these results higher level models are used which are expected to generate results with a lower degree of conservatism. These higher level models are based on the solution of transport equation in space and time for the ingredients, taking into account the complex evaporation kinetics of interacting binary systems and consider the relevant sources in the spraying and post-spraying phase such as evaporation from droplets and treated surfaces. The presentation will contain the description of the overall model, results on plausibility and sensitivity, and the comparison with measured data.
80 Advancing In Vitro Airway Models for Engineered Nanomaterial Genotoxicity Testing
Authors: Evans Stephen J , Fernando Julia , Meldrum Kirsty , Burgum Michael J , Doak Shareen H , Clift Martin J D 
Published: May 2023

Abstract
A primary toxicological focus has been the development of cellular models and exposure systems representative of nanomaterial inhalation due to the inevitable risk of environmental or occupational exposure. This current study compared the genotoxic and immunogenic potential of two nanomaterials: copper oxide (CuO) and zinc oxide (ZnO) and a positive-particle control tungsten-carbide cobalt (WC-Co), in type-II alveolar epithelial cells (A549) utilising cell culture and exposure systems of increasing complexity. Firstly, treatment was undertaken in submerged-culture at a dose range of 1–100 μg/cm2 for all materials. This was repeated with A549s established at the air-liquid interface using a quasi-ALI exposure technique. Finally, complexity of the quasi-ALI exposure was increased with the addition of a dynamic-flow system (Kirkstall Quasi-Vivo,600) allowing media circulation on the basal side of A549 cultures. For all exposures, cytotoxicity, chromosomal damage, and immunogenicity were assessed by relative population doubling, cytokinesis blocked micronucleus assay and interleukin-8 quantification respectively. Compared to the untreated control, significant cytotoxicity (~50%;p&lt;0.05)) was observed in A549s treated with CuO at 100 μg/cm2 following static quasi-ALI exposure. Moreover, both CuO and ZnO demonstrated a significantly increased micronucleus frequency and IL-8 response at 20 and 100 μg/cm2. WC-Co did not promote any (pro-)inflammatory response under any exposure scenario, however genotoxicity was observed in the static and dynamic-flow ALI cultures. Subsequently the variation between the applied exposure scenarios across the chosen test materials has highlighted the importance of considering the impact of the culture environment and exposure system applied when undertaking nanomaterial genotoxicity assessment in vitro.