bluuebunny/crossref_metadata_2025 huggingface dataset:
11 Platinum Speciation in Air Samples
Authors: Sanchez Raquel Garcia , Fisher Paul
Published: May 2023

The health effects of chloroplatinates are generally well recognised and acknowledged by regulators in both EU and USA (Platinum salt sensitivity). But what about Platinum species? Speciation is essential for valid toxicology assessments and speciation studies are lacking in this respect – it’s known that certain Platinum chloro complexes are more sensitising than others. A method for the separation of platinum chloro-complexes and their hydrolysis products has been developed. The different platinum chemical species are separated into their charged compounds in 0.07 M HCl: [PtCl4]2-, [PtCl6]2-, [PtCl3(H2O)]-, [PtCl5(H2O)]- and a zero charged/ bis-aquo compound. The separation was carried via an ion exchange chromatographic column coupled to a quadrupole ICP-MS for the detection of the different anionic platinum chloro-species. A gradient program consisting of a mixture of HCl and HClO4 was used as eluent to ensure the separation of the species. A process has been developed for the analysis of platinum species extracted from air filters in a PGM facility with JM. Although the methodology for speciation is robust, further work needs to be carried out in terms of alternative sample collection to the air filters such as bubblers as the process of sonication, drying and acid contact on the filters does adversely affect the chemical species in solution. A comparison between Platinum speciation in air filters collected form IOM samplers and bubblers will be included in this presentation. This work will generate data to help characterise different workplaces based on the types of task-based exposure.
28 Evaluation of Work-Related Exposures to the Inhalable and Respirable Dust Fraction and to Respirable Quartz
Authors: Koppisch Dorothea , Arnone Mario , Gabriel Stefan
Published: May 2023

Dust is found in the entire environment as well as in working areas. When assessing dust exposure at workplaces, measurements on inhalable and respirable dust are performed. Furthermore, quartz is used as an agent or is released in the form of respirable dust in a number of work processes. Between 2005 and 2016, 35,000 measurements on each dust fraction were performed in the “Measurement System for Exposure Assessment” – MGU. In addition, 15,000 measurements on respirable quartz were performed in this data period. These exposure data on the dust fractions and quartz was stored in the IFA exposure-database MEGA. Statistic evaluations of these data were done according to industrial sectors and work areas. Further grouping criteria like the measurement strategy ("personal measurements" and "stationary sampling") and the sampling time (≥ 2 hours and < 2 hours) help to describe the dust and quartz exposure at work places. Dust and quartz exposures occurring in working areas were analysed for about 20 different industrial sector groups like ceramic and glass industry, foundries, or metalworking and mechanical engineering. These sector groups were further divided in individual sectors and typical tasks performed in these sectors. For example, the tasks stone cutting in stone masonry, mixing and filling in the chemical industry or powder coating in the metalworking sector. The statistical evaluations from the MEGA database are published in IFA-reports about the exposure to inhalable and respirable dust and to quartz for prevention and for retrospective considerations.
30 Reference Materials for the Measurement of Metals in Workplace Air
Authors: Breuer Dietmar , Pitzke Katrin , Nürnberger Franziska , Poprizki Jana , Monse Christian , Monz Christian , Wippich Cornelia
Published: May 2023

For the production of filters coated with metal oxides an aqueous metal salt solution is injected into a hydrogen/oxygen flame of a particle generator leading to the pyrolysis of the metal salts into nano-scaled metal oxide dust. The particles are introduced into a large sampling chamber (20 m³) via a dust tunnel (20 m). So far, the system was tested for Zn, Cu, Pb, Co, Ni, Mn and In but it should be suitable with all metals obtainable as soluble metal salts. For sample generation an eight-fold sampling system was developed for the GSP sampler. The constancy of the flow rate is assured by critical orifices. Up to fourteen of these systems can be operated to produce 112 samples in parallel. Nevertheless, for the production of a reference material a significantly higher number of samples will be needed. To achieve this aim the environmental conditions of the dust generation have to be stabilized for consecutive runs. The major problem was the temperature rise of the dust channel during the particle generation due to the heat of the flame. An additional heater was installed to work at a constant temperature of 30 °C. Three consecutive filter series were manufactured. The achieved temperature constancy of 30± 0.5 °C makes it possible to combine the successive filter series. The loadings of the combined series were Cobalt: 3.25±0.058 µg/filter, Nickel: 13.78±0.23 µg/filter, Lead: 109.5±3.0, Copper: 9.65 ±0.18 µg/filter and Zinc: 32.66±0.72 µg/filter.
39 Systematic Review of Validation Studies of the ECETOC Targeted Risk Assessment V3 Tool for Worker Exposure Estimation Under Reach
Authors: Urbanus Jan , Li Qiang , Marsh Dave , Henschel Oliver , van de Sandt Paul , Wormuth Matthias , van Rooij Joost , Noij Dook , Money Chris , Welsted Tim , Cuciureana Andreea
Published: May 2023

The Targeted Risk Assessment tool (TRA) has been widely used since 2010 in the development of REACH registration dossiers for classified chemical substances to estimate worker exposures (inhalation, dermal) across manufacturing and use operations in supply chains in Europe. The TRA is a Tier-1 tool which produces simplified exposure predictions based on limited inputs and intended to be conservative. The current version (3.1) of the TRA was released in 2012 and has been built into ECHA’s CHESAR tool. A number of studies have been published of TRA-generated exposure predictions compared with workplace measurement data and presenting conclusions about the tool performance. Most publications covered only a subset of the tool outputs. A group of ECETOC exposure assessors assembled inventories of published comparisons over the period of 2010-2020 (approximately 120 workplace scenarios for long-term inhalation, 40 scenarios for peak inhalation and 80 scenarios for dermal exposure) to systematically review the tool performance. The analysis has allowed to draw more robust conclusions about the performance of specific aspects of the tool, such as base level estimates and effectiveness of local exhaust ventilation, to either reinforce the conclusions of conservatism (majority of scenarios) or recommend changes to tool settings in a future version (minority of cases) to better match the tool’s intent. A short overview of the comparisons will be presented, as well as the planned changes to the tool settings.
88 Occupational Exposure to Metals Among Battery Recyclers in France: Biomonitoring and External Dose Measurements
Authors: Hanser Ogier , Melczer Mathieu , Remy Aurélie Martin , Ndaw Sophie
Published: May 2023

In battery-recycling facilities, exposure to trace elements may occur through inhalation of contaminated dust or vapor emanating from the treatment processes. Thus, biomonitoring coupled with air measurements, appeared to be a relevant approach to assess exposure of battery recyclers. While lead exposure has been quite well covered in the literature, in contrast, data on exposure to other elements contained in batteries are lacking. The aim of this study was to characterize the exposure of French battery recyclers to multiple elements using biomonitoring and airborne measurements. Eighty-six workers participated in the study. Pre-shift and post-shift urine samples and personal airborne samples were collected during the working week. Inductively coupled plasma mass spectrometry was used to analyze 7 trace elements in both type of sample: Cd, Co, Cr, Li, Mn, Ni, Pb. Results showed battery recyclers to be mostly exposed to Cd, Co, Li, Mn and Ni. Urinary sample analysis indicated exposure to Cd and Co, with levels measured at up to 27.6 and 3.34 µg/g of creatinine, respectively. Cd, Co, Li, Mn, and Ni were detected at high levels in air samples, especially near the treatment facilities, with airborne cadmium levels of up to 79.4 µg/m3. Administrative and sorting workers were exposed at lower levels than maintenance, treatment, and dismantling workers. The data presented provide valuable information on exposure to trace elements for battery recyclers. They also highlight the need to improve both collective and individual protective measures, which were not sufficient in the participating companies.
72 Elemental Screening of Welding Fumes by Ed-Xrf Using a Standardless Calibration Algorithm
Authors: Butler Owen , Musgrove Darren
Published: May 2023

X-ray fluorescence (XRF) is an ideal analytical technique for rapid elemental analysis in supporting forensic analysis, for exposure assessments and for product compositional analysis. Standardless calibration algorithms are widely used in modern XRF systems so providing, in many cases, near quantitative analysis, without recourse to needing matrix-matched standards. However if available, matrix standards can be used to further improve the performance of such algorithms and so provide better quantitative data. In this presentation, XRF analysis of bulk welding fume samples was performed, in supporting fume compositional studies required for product data sheets, and aided by the analysis of reference welding fume standards previously characterised by ICP-AES.
89 Improvements to a Method for the Determination of Hexavalent Chromium in Workplace Air
Authors: Forder James , Musgrove Darren , Butler Owen
Published: May 2023

ISO 16740:2005 specifies an ion chromatographic method for the determination of the time-weighted average mass concentration of hexavalent chromium in workplace air and is applicable to the determination of masses of 0,01 micrograms to 10 micrograms of hexavalent chromium per sample, without dilution. For a nominal 1 cubic metre air sample, this equates to a measurement range of between approximately 0,01 micrograms per cubic metre to 10 micrograms per cubic metre, suitable for assessing exposures in plating or weld shops. However alkaline extractants, required to liberate insoluble chromates from air samples collected in paint shops, can be contaminated with trace levels of chromium thereby negating the inherent sensitivity of this method. Work to address this issue, by sourcing and testing cleaner reagents, will be presented.
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

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

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

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

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

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

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

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

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

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

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

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

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<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.
116 A Phase-Gate Nano-Risk Governance Approach Reflecting International Standards
Authors: Jensen Keld Alstrup , Liguori Biase , Ribalta Carla , Shandilya Neeraj , Bakker Martine , Suarez-Merino Blanca , Porcari Andrea , Delpivo Camilla , Bleeker Eric , Pohl Anna , Nymark Penny , Nowack Bernd , Franken Remy , Hristozov Danail , Fransman Wouter
Published: May 2023

Risk governance, sustainability and safety-by-design have high attention in current research projects and policy. In the EU H2020 Gov4Nano project, we refined the EU H2020 caLIBRAte phase-gate nano-risk innovation governance framework, its guidance and expanded the list of supporting risk governance tools. Stakeholder wishes were mapped from previous projects and consultations made within Gov4Nano and across the two other EU H2020 NMBP-13 governance projects (NANORIGO and RiskGone) and considered in the refinement. The revised framework considers three pre-defined phase-gate models for minor (fast-track/low risk), intermediate (medium risk) and novel (high-risk) developments. The guidance was further elaborated to direct users though sustainability and safety-by-design considerations and risk mitigation actions. ISO21505 was used as the backbone for the risk governance framework. The approach allows design of the specific nano-risk governance project and information requirements for decision-making. The list of recommended nano-risk governance tools was expanded and selected considering their reliability and performance. An important step in this process was an evaluation of tools made under the umbrella of the OECD (ENV/CBC/MONO(2021)23; ENV/CBC/MONO(2021)27/REV; ENV/CBC/MONO(2021)28; ENV/CBC/MONO(2021)29/REV) and development of a new tool assessment framework called TRAAC (Transparency, Reliability, Accessibility, Applicability and Reliability). Limitations in application domains remains an issue for future developments. The approach and tools are made accessible via a nano-risk governance portal produced by the three NMBP-13 projects (http://nanoriskgov.eu/).  

Funding: European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 814401.
123 Finding Optimal Methods for SbD Hazard Testing of Nanomaterials: The Effect of Cell Model and Exposure Method on Cytokine Response
Authors: Ruijter Nienke , Boyles Matthew , Carrière Marie , Katsumiti Alberto , Candalija Ana , Cabellos Joan , Ayerbe Rafael , Rodriguez Isabel , Marshall Jessica , Cassee Flemming , Braakhuis Hedwig
Published: May 2023

The concept of safe-by-design (SbD) can help toxicologists and risk assessors to keep pace with the rapidly expanding field of nanotechnology. As part of SbD, the hazard potential of a new nanomaterial (NM) is identified at the first stages of product development. For this, simple yet predictive toxicity assays are crucial. We investigated the suitability of several in vitro models and exposure methods to predict the human (pulmonary) inflammation potential of NMs. Four silica NMs were selected of which in vivo pulmonary toxicity ranking had previously been established: DQ12 (quartz) > NM-203 (fumed silica) > Colloidal silica > Silanized colloidal silica. Several cell types including a 3D human airway epithelial model, lung epithelial cell lines, and immune cell lines, either in mono- or co-culture were exposed to the four materials either in a submerged setting or at the air-liquid interface (ALI). After 24 hours of exposure, cytokine response was assessed using either 13-plex LegendPlex, ELISA, or qPCR, and toxicity rankings were compared. The results indicate differences in sensitivity between cell models and exposure methods. Submerged exposure of a cell-line seems a suitable first tier for SbD hazard testing in case of NMs that can easily be dispersed. For NMs that are not compatible with submerged testing, ALI exposure might be needed. Higher tier testing might be used to confirm the ranking.
128 Exposure to soot, Measured as Black Carbon and PAH, in Swedish Chimney Sweeps
Authors: Klang Therese , Strandberg Bo , Molnár Peter , Johannesson Sandra , Tinnerberg Håkan
Published: May 2023

The overall aim of our research is to study chimney sweeps exposure to soot to be able to give recommendations on how to effectively reduce the exposure. To do this a suitable method to study soot exposure is required. In this study we use a new method to study the personal airborne exposure to soot measured as black carbon (BC). BC is measured with a AethLabs MA200 micro aethalometer with a flow rate of 100 mL/min and sampling time of 1 min. By using a direct-reading instrument we aim to identify variability in exposure levels during the workday, and potential work tasks contributing to elevated exposure to soot. The study includes 20 chimney sweeps performing black sweeping in Sweden and BC is measured for eight workdays for each individual. During these days individuals also fill out a diary of work tasks performed. To assess the value of the BC levels, airborne polycyclic aromatic hydrocarbon (PAH) is also measured with personal sampler for particulate- and gas phase PAH. PAH is measured in parallel with BC during one workday. Preliminary results show variability of BC levels between different individuals as well as different workdays for the same individual. We are also able to link BC levels with work tasks from the diaries. Significantly elevated PAH levels and especially the particle-bound PAHs, including the carcinogenic benzo(a)pyrene, were observed in most samples.
132 Colorimetric Assessment of Household Settled Dust Captured on Silicon Nanomembranes
Authors: Romanick Samantha , Cashion Garrett , Madejski Greg , Elder Alison , McGrath James
Published: May 2023

Humans spend 70-90% of their time indoors, however, there is a significant lack of knowledge regarding human exposure to microplastic particles and fibers (MPs) within the indoor environment. Fibers make up more than 90% of household settled dust worldwide and have been found in indoor air. Studies have identified MPs larger than 50 micrometers in indoor dust, but these are unlikely to be respirable and little information is available regarding smaller airborne particles. It is evident that humans are inhaling these particles as they have been found in excised diseased and healthy human lung tissues. We have developed methods to identify plastic particles in settled household dust larger than one micrometer in diameter by distinguishing plastic from cellulosic, proteinaceous, and inorganic materials using two different stains, Nile Red for plastics, and Trypan Blue for cellulosic materials. Proteinaceous and inorganic materials remain unstained. Household settled dust is collected onto silicon nitride nanomembranes where in situ analysis of particles can be characterized. The innovative use of nanomembranes allow for particle capture and multiple analyses to take place on the same substrate. Particle analysis via colorimetric staining and imaging is followed by polymer identification via Raman spectroscopy and subsequently characterized via scanning electron microscopy for size and surface morphology. Using this innovative approach, microplastic particles larger than one micrometer in diameter have been identified in all settled dust samples.
140 A Framework for Grouping Inhaled Multi-Component Nanomaterials to Streamline Hazard Assessment
Authors: Stone Vicki , Oomen Agnes , Johnston Helinor , Hristozov Danail , Schmidt Otmar , Stoeger Tobias , Ramos Juan Antonio Tamayo , Aparicio Santiago , Murphy Fiona
Published: May 2023

The GRACIOUS Framework (www.h2020gracious.eu) supports the grouping of nanomaterials to streamline hazard testing of nanomaterials.  The GRACIOUS Framework includes a template to generate grouping hypotheses based upon use and life cycle stage (to inform exposure route), physicochemical properties (what they are), fate or toxicokinetics (where they go) and hazard (what they do). The gathering of evidence to test these hypotheses was supported by tailored Integrated Approaches to Testing and Assessment (IATAs). Subsequent NMBP-16 projects have developed the hypothesis template further for multicomponent nanomaterials. Modifications include additional information requirements to accommodate the complexity of composition (what they are) and enhanced properties, with an aim to incorporate the relationship of these to the mechanism of hazard.   Furthermore, the template considers potential for the components to dissociate, disintegrate or dissolve, with different kinetics, leading to a complex exposure scenario both in lung lining fluid and inside cells. This knowledge informs the hazard assessment (whether hazard is driven by the intact multicomponent nanomaterial or various components) and whether interactions between the components may lead to antagonism, synergism or potentiation of response.  Hazard assessment outcome can then inform Safe-by-Design modifications. The template has been adapted to formulate clear questions needed to test all aspects of the hypothesis, with these questions being used to formulate the IATA.  Case studies of different multicomponent nanomaterials are being used to inform the design process, and demonstrate its usefulness.

Funding acknowledgement European Commission Horizon 2020 for GRACIOUS, SUNSHINE, HARMLESS and DIAGONAL, Grant Agreement No. 760840, 952924, 953183 953152 respectively.
5 Exploring the Carcinogenic Potential of Nanoplastics
Authors: Domenech Josefa
Published: May 2023

Nanoplastics are all around us. Therefore, humans are unavoidably and continuously exposed to them. Among other effects, the accumulation of nanoplastics in tissues and organs has been reported. Due to their persistence, nanoplastics can trigger effects that have been related to the carcinogenic process. Knowing that carcinogenesis is a long-term process, the ubiquity and persistence of nanoplastics, along with the continuous exposure, make them potential carcinogens. Traditionally, short-term genotoxicity tests were performed to assess the carcinogenic potential of agents owing to the well-known capacity of DNA damage and mutation as initiators. However, carcinogenesis is a multi-stage process that involves initiation, promotion, and progression events. The validated Bhas-42 cell transformation assay allows the in vitro simulation of the in vivo initiation and promotion stages of carcinogenesis, thus, the detection of agents with initiating and/or promoting activity. Using the novel Bhas-42 in vitro approach, the carcinogenic potential of polystyrene (PS), polyethylene terephthalate (PET), and polylactic acid (PLA) nanoplastics has been assessed. These plastic types are among the most represented in our daily life as food packages, building insulation, plastic films, electrical and electronic equipment, inner liner for fridges, eyeglasses frames, cleaners, etc. Preliminary results indicate the lack of PS’ carcinogenic potential, which agrees with the reported literature. However, an evident dearth of knowledge about other types of MNPLs, such as PET and PLA, exists. Ongoing research will shed light on the carcinogenic risk of these non-studied nanoplastics to date that could pose a risk to human health.
53 Cognitive Decline, Dementia and Air Pollution: A Report by the Committee on the Medical Effects of Air Pollutants
Authors: Maynard Robert , Carare Roxana , Grigg Jonathan , Fox Nick , Love Seth , Mudway Ian , Shaddick Gavin , Delgado-Saborit Juana Maria , Guercio Valentina , Earl Naomi , Mitsakou Christina , Doutsi Artemis , Exley Karen , Robertson Sarah , Douglas Philippa , Gowers Alison
Published: May 2023

Dementia is an umbrella term for a range of conditions that affect how the brain works and, in particular, the ability to remember, think and reason. It mainly affects older people, both men and women, and gets worse over time. In recent years, there has been growing interest in the possibility that exposure to outdoor air pollution could increase the risk of dementia. COMEAP reviewed epidemiological and experimental studies and concluded that it is likely that air pollution contributes to a decline in mental ability and dementia in older people. The most likely way this occurs is through effects on the circulatory system. It is known that air pollutants, particularly fine particles, can affect the heart and blood vessels, including those of the brain. These effects are linked to vascular dementia, which is caused by damage to the blood vessels in the brain. Experimental studies suggest that air pollution may also stimulate immune cells in the brain, which can then damage nerve cells. It is also likely that some nano-sized (ultrafine) particles can enter the brain, either by transport along the olfactory nerve or by entering the circulation and crossing the blood-brain barrier. These particles may cause direct damage. Nonetheless, based on the available evidence, it does not seem likely that this is an important mechanism for the development of dementia. Recommendations were made for further research which would help develop the evidence on this important topic.