bluuebunny/crossref_metadata_2025_split huggingface dataset:
162 Keynote: Adverse Outcome Pathways – a Framework for Designing Novel Approach Methods for Safety Assessment
Authors: Halappanavar Sabina 
Published: May 2023

Abstract
The fast evolving technologies, the search for new chemicals and synthesis of substitutes for the existing chemicals, are posing unprecedented challenges on regulatory agencies that have mainly relied on toxicity testing in laboratory animals to ensure safety of humans and the environment from potential exposure to these substances. In response, a new and well-intended trend to reduce, refine and replace animal testing that are both time and resource intensive with animal alternatives called the New Approach Methodologies (NAMs) that are faster, cheaper, sensitive, and mechanisms-based, has been introduced and widely embraced by the scientific community. However, strategies that help identify and prioritize fit-for-purpose NAMs schemes involving test models, toxicity endpoints, and specific assays for the hazard assessment, as well as strategies that enable validation of their scientific relevance for the regulatory acceptance are lagging behind. As a consequence, the regulatory acceptance of NAMs in decision making is far from reality. This presentation will summarise the current status of NAMs in regulatory toxicology and the role of Adverse Outcome Pathways (AOPs) in the design and development of NAMs, with a specific focus on nanotoxicology.
21 Toxicity of Aircraft Engine Emissions in Calu-3 Human Cells in Air-Liquid Interface Condition.
Authors: Melzi Gloria , van Triel Jos , Gerlofs-Nijland Miriam , Cassee Flemming R 
Published: May 2023

Abstract
Particulate Matter (PM) emissions from aircraft engines adversely affect air quality around airports, contributing to public health concerns for airport workers and neighbouring communities. In this research, PM was collected from the exhaust of turbine engine after combustion of various types of aircraft fuels, including conventional fuel types Jet A and Jet A1, and more sustainable alternatives with relative low levels of aromatics. PM samples’ toxicity was studied in vitro by air-liquid interface (ALI) exposure of Calu-3 cells in monoculture and co-culture with macrophages (differentiated THP-1 cells). Cells were exposed to PM suspensions (250 µg/mL) using a cloud-based ALI exposure system and analysed 24-hours after exposure. DNA damage was detected through Comet assay in cells exposed to Jet A and Jet A1 samples in absence of cytotoxicity; co-incubation with endonucleases-III and formamidopyrimidine-DNA glycosylase showed that this was not associated with oxidation of DNA bases. Real-Time PCR was performed to investigate the expression profile of genes involved in oxidative stress and DNA repair pathways. Heme Oxygenase 1 gene, Mucin 5AC, and Angiotensin-Converting Enzyme 2 were modulated in the same samples where DNA damage was present. No differences were shown in the pro-inflammatory interleukine-8 secretion among the samples. Most of the PM samples generated using jet fuel with high content of aromatic compounds induced enhanced genotoxicity, suggesting that strategies lowering aromatic content may also result in less toxic PM emissions.
Funded by Horizon2020 – Research of Aviation PM Technologies, mOdelling and Regulation (RAPTOR), grant number 863969.
27 Acute and Chronic Effects on Inflammatory Markers by Quartz and Particle Exposure in the Iron Foundry Environment
Authors: Hedbrant Alexander , Engström Christopher , Andersson Lena , Eklund Daniel , Westberg Håkan , Persson Alexander , Särndahl Eva 
Published: May 2023

Abstract
Inflammation is a central mechanism in the aetiology of particulate matter (PM)-associated diseases, including cardiovascular diseases (CVD). Both acute inflammatory events and chronic low-grade inflammation due to exposure contribute to adverse health effects of exposure. The aim of the current study was to determine if current exposure levels to respirable quartz or dust at Swedish iron foundries induce acute or chronic systemic inflammatory responses, using biomarkers broadly classified into three groups; 1) general markers of inflammation, 2) novel inflammatory markers of CVD, and 3) NLRP3 inflammasome-related markers. Exposure to respirable dust and quartz was determined during a workday in 40 iron foundry workers, and blood samples were collected before and after workshift. The sampling procedure was repeated approximately three weeks later. To determine acute effects of exposure, the over-shift difference in biomarker levels were studied, whereas to study chronic effects, the average morning sample biomarker levels were correlated to the average exposure levels of the two sampling occasions. We found that biomarkers of the NLRP3 inflammasome correlated to quartz exposure, including acute and chronic effects on ex vivo caspase-1 activation in monocytes, acute effects on plasma levels of IL-18, and chronic effects on IL-1Ra plasma levels. Our results suggest that the present exposure levels to respirable quartz in the Swedish iron foundries, which were below the Swedish occupational limits, may trigger inflammasome activation in the exposed workers.
44 Dual Proteomic Exploration of the Mechanisms Underlying Brake Dust-Induced Impairment of Phagocytic Capacity in Macrophages
Authors: Selley Liza , Franco Catarina , Martin Maria Guerra , Morone Nobuhiro , Purves Jo , Morrissey Julie , MacFarlane Marion 
Published: May 2023

Abstract
Exposure to brake abrasion dust (BAD) reduces the phagocytic capacity of macrophages, possibly contributing to increased risk of airway infections in polluted regions. The mechanisms that underlie this toxicity remain to be characterised and, considering that pre-exposure of respiratory bacteria to alternative traffic-related particulates enhances their dissemination into the lungs of mice, may include changes in the virulence of pathogens themselves. Dual proteomic screening (TMT-labelled UPLC-MS) was performed for RAW 264.7 monocyte-derived macrophages and S.aureus (USA300) following 24h exposures to BAD (0-16 ug/ml). In S.aureus, expression of agr-regulated, anti-leukocytic virulence factors (lipases, staphopains, hemolysins) increased in a dose-dependent manner as well as proteins required for epithelial invasion (serine proteases) and antibiotic resistance. RAW 264.7 exhibited a predominantly adaptive response following exposures, enhancing expression of proteins required for metal homeostasis, NFkB-mediated inflammation and endosomal maturation. However, disrupted expression of proteins required for electron transport chain activity and Fe-S cluster synthesis accompanied significant dose-dependent reductions in ATP production (60-82%, p&lt; 0.001) while transition electron microscopy (TEM) detected disrupted mitochondrial membrane morphology. TEM also identified reductions in pseudopodia length in exposed macrophages (54% shorter than control, p&lt; 0.05), highlighting a mechanism by which BAD exposure may decrease the incidence of host-pathogen interactions. These data highlight dual mechanisms by which BAD emissions could impair bacterial phagocytosis and enhance susceptibility to airway infections. Through avoidance and suppression of host anti-microbial mechanisms by the bacteria and, as actin polymerisation depends on ATP availability, loss of mitochondrial function and downstream pseudopodia projection in macrophages.
47 Safe-by-Design Advanced Materials: A case Study on Paint Formulation
Authors: Shandilya Neeraj , Isaxon Christina , Persson Michael , Persson Daniel , Moerman Marcel , Hongisto Vesa , Ledwith Rico , Saccardo Angela , Meldrum Kirsty , Clift Martin J D , Fransman Wouter 
Published: May 2023

Abstract
Paint formulations are complex mixtures of both dissolved and particulate components, both organic and inorganic. Amorphous silica nanoparticles are included to make the paint layer dirt-repellent. Over entire life cycle of the paints containing such silica nanoparticles, however, their complex multicomponent composition may raise several concerns as to their hazard when exposed to humans and environment, notably due to the potential release of the incorporated nano-objects. To mitigate such concerns, several Safe-by-Design target specifications can be performed to provide revised/modified paint formulations with reduced potential risk. Within EU H2020 funded project, HARMLESS (grant agreement 953183), a specific industrial case study focuses on worker exposure measurement at the industrial production site of silane modified silica nanoparticles and consumer exposure measurement during sanding of the painted surfaces containing such silica nanoparticles. First results indicate that the tested paint samples (with and without silica nanoparticles) have strong tendencies to generate airborne nano-objects during their sanding. However, the fraction of silica in the overall chemical composition of the airborne nano-objects is currently being investigated. A fraction of the dust generated during the paint sanding is being analysed for its hazard via advanced in vitro approaches combined with a battery of toxicological endpoint analyses. Based on the results, if the exposure concentration of silica nanoparticles is found to be exceeding its nano reference value (i.e. 40,000 cm-3 TWA) and exhibits deleterious biological impact, the size and surface of silica nanoparticles will be modulated accordingly by keeping an optimum balance between their functionality and risk
50 Human Hazard Assessment of Nanomaterials: Supporting Risk Decision Making Through Interlaboratory Trial Data
Authors: Burgum Michael , Yamani Naouale , Longhin Eleonora , Mariussen Espen , Rundén-Pran Elise , Sosnowska Anita , Puzyn Tomasz , Clift Martin , Dusinska Maria , Doak Shareen 
Published: May 2023

Abstract
The prevalent application of engineered nanomaterials (ENMs) has led to an extensive effort to develop tools facilitating their risk assessment and management. This interlaboratory trial (encompassing two laboratories) sought to investigate the genotoxic impact of ENMs using the hypoxanthine phosphoribosyltransferase (HPRT) forward mutation assay and in vitro cytokinesis-blocked micronucleus (CBMN) assay, utilising harmonised protocols. In the CBMN assay, human lymphoblast (TK6) cells were exposed to zinc oxide (ZnO), titanium dioxide (TiO2) and tungsten carbide-cobalt (WC/Co) for 24-hours after which 1000 binucleated cells were scored for micronuclei (n=2). For the HPRT assay, TK6 and mouse fibroblast (V79) cells were exposed to ZnO, TiO2, WC/Co, CuO and Nanocyl-CNTs for 24-hours after which 600 wells were scored for point mutations (n=2). Significant cytotoxicity and micronuclei frequency was reported following ZnO exposure (20µg/ml). Significant micronuclei induction was reported following WC/Co exposures (2-fold over control, 100µg/ml). No significant mutagenicity was detected with ZnO or TiO2; both laboratories observed significant cytotoxicity following exposure to ZnO (20µg/ml; 37% reduction in cell viability). In the second interlaboratory trial CuO induced significant cytotoxicity (36% reduction in viability: 0.5µg/ml), and a 32-fold increase in mutagenicity. The Nanocyl induced a 6-fold increase in mutagenicity. The data generated here has shown good statistical concordance between laboratories and has highlighted a promising route forward in supporting risk decision making for ENMs. The authors would like to acknowledge this research has received funding from the European Union’s Horizon 2020 research and innovation program for the RiskGONE project, grant agreement #814425.
56 Monitoring Diesel Exhaust Particles by Lock-in Thermography
Authors: He Ruiwen , Gunasingam Gowsinth , Petri-Fink Alke , Rothen-Rutishauser Barbara 
Published: May 2023

Abstract
Diesel exhaust particles (DEPs) can deposit onto the respiratory epithelial surface upon inhalation. In vitro exposures of various lung models to DEPs have been performed under the air-liquid interface (ALI) conditions in previous studies, however, methods to quantify DEPs onto/into cells during and after exposure are still challenging and not well established. In our study, a new particle detection system, i.e. lock-in thermography (LIT), was explored. LIT is a heat- sensitive imaging method that applies the light illumination to induce the heat of carbon-based particles for detection. By testing a standard DEPs sample (SRM2975), a positive linear relationship (R2 = 0.98) was established between the thermal emission signals and DEPs levels ranging from 0 to 30 µg/mL, with limit of detection (LOD) at 1.00 µg/mL. Moreover, phototoxicity tests showed that no cytotoxic effects were observed on human lung epithelial (A549) cells upon excitation light wavelength of 525 and 660 nm for 1 – 2 mins. Taken together, it suggests that the LIT can be used for detecting DEPs exposed with A549 cells at the relatively low concentration. Further improvement and optimization of the LIT system are ongoing to evaluate DEPs exposed lung cells.
58 Setting Targets for Particles in Outdoor Air: Advice from the Committee on the Medical Effects of Air Pollutants (Comeap)
Authors: Hansell Anna , Kelly Frank , Walton Heather , Mitsakou Christina , Earl Naomi , Doutsi Artemis , Exley Karen , Gowers Alison 
Published: May 2023

Abstract
The Environment Act (2021) requires the government to set at least one long-term air-quality target, as well as a target for fine particulate matter (PM2.5) air pollution. COMEAP provided independent expert advice to the Department for Environment, Food and Rural Affairs (Defra) to inform the development of targets to reduce both the annual average (mean) concentration of PM2.5 in ambient air and long term population exposures. COMEAP’s advice includes that: a focus on reducing long-term average concentrations of PM2.5 is appropriate evidence indicates that PM2.5 pollution can have harmful effects on people’s health at low concentrations reducing concentrations to, or below, the World Health Organization’s new Air Quality Guideline (5 µg/m3) would benefit public health available studies have not indicated a threshold of effect below which there is no harm reducing exposure of the whole population would achieve the greatest overall public health benefit some individuals or groups are more at risk, but it might be difficult to reflect this in a national targets framework the health benefits of reducing other pollutants, such as nitrogen dioxide and ozone, should not be overlooked. In response to Defra’s evidence report explaining the rationale for its proposed targets, COMEAP: recommended that Defra should consider roles in continuing to improve air quality, even where legally binding targets are met suggested that interim targets would be important to ensure early progress and maximise health benefits stressed the importance of considering inequalities noted that international engagement will be required
63 A Case for Amorphous Silica Nanoparticle Exposure in the Development of Chronic Kidney Disease of Unknown Etiology
Authors: Rogers Keegan , Stem Arthur , Roncal Carlos , Johnson Richard , Brown Jared 
Published: May 2023

Abstract
We have hypothesized that sugarcane burning in developing countries contributes to an endemic kidney pathology in agricultural workers called chronic kidney disease of an unknown etiology (CKDu). Elemental analysis shows that sugarcane stalks contain a high percentage of amorphous silica (SiO2). Therefore, we hypothesized that burning of sugarcane generates silica nanoparticles (SiNPs) that present an inhalation hazard to these agricultural workers. To determine if SiNPs are present in sugarcane ash and kidney biopsies from agricultural workers, we utilized single particle inductively coupled plasma mass spectrometry and found SiNPs, which ranged in size from 190-212 nm, in sugarcane ash. In a small cohort of CKDu patients from El Salvador and Mexico, we found a significant increase in the number of SiNPs in their kidney biopsies within a similar size range as observed in sugarcane ash. Additionally, Wistar rats exposed to sugarcane ash intranasally for 24 weeks developed focal injury in the tubulointerstitium and glomeruli with deposition of SiNPs in the kidney. To further determine the cellular effects of SiNPs, we exposed human proximal convoluted tubule (PCT) cells to sugarcane ash, de-silicated ash, or sugarcane ash derived SiNPs. Despite not being directly cytotoxic to PCT cells at 24 hrs, SiNPs were taken up and generated reactive oxygen species. Vimentin staining confirmed PCT cells underwent epithelial-mesenchymal transition (EMT) following treatment with ash or SiNPs but not with de-silicated ash. These findings suggest SiNPs present in sugarcane ash are capable of driving EMT in PCT cells potentially contributing to a CKDu phenotype.
78 Nano Exposure Quantifier (NEQ) - A Quantitative tool for Assessing Exposure in the Workplace
Authors: Franken Remy , Goede Henk , Shandilya Neeraj , Ge Calvin , Kalkman Gino , Otto Marlies , van Venrooij Bart , van Someren Eugene , Fransman Wouter 
Published: May 2023

Abstract

Background
The EU Horizon2020 “safe-by-design for Nano” (SBD4Nano) project aims to develop a tool to assist users in the safe-by-design process and decisions to reduce risk as a result from working with- or using newly developed products containing manufactured nanomaterials (MNs). Therefore, TNO set out to develop an easy-to-use quantitative exposure assessment tool that helps users with different levels of expertise to reduce the exposure from MNs following an integrated Tiered safe-by-design approach.

Method
Based on previous projects, literature, expert knowledge, a Tiered set of model determinants and corresponding calculations were integrated into a conceptual model. Also, an exposure database based on the EU GRACIOUS template was created containing a large set of exposure measurements collected from diverse literature studies. Machine learning was applied to these exposure measurements to validate and refine the model. Lastly, a safe-by-design module was added to assist users modify their material or process design to reduce exposure.

Results
An online tool is realized that will be freely available on https://diamonds.tno.nl/#neq. The NEQ offers a Tiered approach by smartly adapting the questions based on the depth of information the user can provide allowing anywhere between a Tier-1 and a Tier-2 approach. After answering questions, the user is presented an exposure estimate including uncertainty of the current design. The user is guided to enter a new design that reduces the exposure and/or its uncertainty.
90 Graphene – Exposure and Emissions at Two Pilot Plants
Authors: Tinnerberg Håkan , Storsjö Tobias , Isaxon Christina 
Published: May 2023

Abstract
Graphene is a nanomaterial suitable for a wide variety of applications. The industrial production and use of graphene is, hence, increasing rapidly. The main challenge in assessing graphene exposure is that graphene is a carbon structure, making it comparable to look for a needle in a haystack. We have explored the possibility to analyze elemental carbon and black carbon as a measure of personal graphene exposure. Exposure and emission measurements for graphene were conducted at two pilot plants using on- and off-line techniques. One plant produces graphene, up to 10 tons per year, using liquid exfoliation technique. The other plant uses graphene to coat paper in a conventional roll-to-roll process. The measurements were conducted both stationary (in the emission zone and in the background) and as personal measurements (in the breathing zone of the workers). We have analyzed elemental carbon and black carbon as a measure of the personal exposure. In the emission and background zone we have measured number of particles and lung deposited surface area concentration of particles &lt;300nm, mass concentration, and we have collected samples for electron microscopy analysis. The exposure was in general low, but we identified tasks with an increase emissions. Measurements of elemental carbon is a promising technique for occupational hygienists to find possible exposure to graphene.
112 Use of a Human Bronchial Epithelium Model to Assess the Impact of PM2.5 Exposure on the Severity of Viral Infections
Authors: Chivé Chloé , Martin-Faivre Lydie , Eon-Bertho Alice , Garcia-Verdugo Ignacio , Baeza-Squiban Armelle 
Published: May 2023

Abstract
Epidemiological studies have shown an association between exposure to fine particles (PM2.5) and the severity of respiratory infections such as influenza and COVID-19. PM2.5 and viruses target the bronchial epithelium suggesting that exposure to PM2.5 could make it more susceptible to infections. Our project aims to study the impact of PM2.5 on the severity of influenza virus and decipher the underlying mechanisms. We used a human bronchial epithelium grown at air-liquid interface (ALI) and characterised its responses to a single 24h exposure to PM2.5 at ALI at 5, 10 or 20 µg/cm². Particles induced the expression of the pro-inflammatory cytokines IL-6 and IL-8 as well as IFN-β showing an impact on the antiviral signaling pathway. When bronchial epithelium is infected with influenza virus (murine H3N2) after 24h exposure to PM2.5, there is an increase in LDH activity in the apical secretome associated with a trend towards increased expression of the viral protein M2 as well as an enhanced release of mediators of the antiviral defense (IL-6, IL-8, RANTES), compared to the non-exposed epithelium. These results suggest that pre-exposure to PM2.5 may increase the severity of viral infection in association with an increase of viral replication which needs to be confirmed subsequently by virus titration. Antiviral signaling is now investigated and the effects of repeated exposures of the bronchial epithelium to PM2.5 on the severity of viral infection are also explored.
This work is support by the Foundation for Medical Research, French Environment and Energy Management Agency and DIM Qi2.
115 Fibre-Aerogel-Mats for façade Insulation: How to Guide SSbD Development by Screenings?
Authors: Wohlleben Wendel , Battista Veronica Di , Guenter Eva , Ribalta Carla , Jensen Keld , Saccardo Angela , Meldrum Kirsty , Clift Martin , Baun Anders , Demokritou Philip 
Published: May 2023

Abstract
The HARMLESS project focusses upon assessment approaches to support Safe-and-Sustainable-by-Design (SSbD) development of advanced materials (AdMa). Case studies comprise several industry sectors. Specifically for the construction sector we study façade insulation by fibre-aerogel-mats. Beyond the relatively simpler mono-component organic aerogels presented earlier (Keller et al. 2021), here we deal with multi-component materials: Glass fibers provide structural integrity for the silica-based aerogel that provides the thermal insulation performance, though is coated by organosilane as a hydrophobizing agent to prevent moisture uptake. Optionally, an additional inorganic coating can be applied to enhance mechanical stability. Here we explored this wide SSbD design space by four industrially relevant SSbD-versions of fibre-aerogel-mats; these were ranked and compared against each other as well as conventional insulation material (i.e. stone wool). We assessed the release by performing several typical occupational operations under clean-air conditions within a laboratory setting. Up to 106/ccm particles are released, with respirable aerodynamic diameters. We collected the dust and assessed the structure and behavior with respect to its biological reactivity and biodissolution, focusing on the screening and ranking of inhalation hazards. The data on exposure and hazard was complemented by data on functionality in the intended use, where all SSbD versions performed significantly better than the conventional alternative. The new data refines the risk screening and categorisation schemes for advanced materials, including Early4AdMa (RIVM 2022), AdmGRID (Kennedy et al. 2019), InnoMat.Life (Wohlleben et al. 2022) and an environmental risk screening (Arvidsson et al. 2022).