bluuebunny/crossref_metadata_2025_split huggingface dataset:
143 Urinary Metals Exposure and Oxidative Stress Biomarkers in Nanotechnology Workers: Results from the Nanoexplore Project
Authors: Bellisario Valeria , Squillacioti Giulia , Panizzolo Marco , Ghelli Federica , Mariella Giuseppe , Canu Irina Guseva , Bergamaschi Enrico , Bono Roberto 
Published: May 2023

Abstract
Exposure to metal oxides nanomaterials (NMs) might trigger adverse health effects. NMs can generate Oxidative Stress (OS), causing redox effects detectable in urine through suitable biomarkers. We evaluated the cross-sectional association of urinary OS biomarkers with urinary metal concentrations, using data collected in the multicenter international study NanoExplore. One hundred forty-one workers were recruited at three R&D and four industrial facilities employing NMs in different processes (paints/coating[PC];construction chemicals[CC]). Only 129 workers had complete data and, based on the personal work-shift exposure to NMs, they were classified as unexposed workers (n=41), workers with negligible/low exposure (n=37), and with moderate/high exposure (n=51). OS biomarkers (IsoP,MDA,TAP) and metals (27Al,47Ti,52Cr,118Sn) were quantified in urine samples collected before and after exposure monitoring campaign (2-4 work-shifts). Between-group comparisons were performed with non-parametric tests according to the data distribution. Highly exposed workers had significantly higher pro-oxidant (IsoP and MDA,p&lt;0.005) and antioxidant (TAP,p&lt;0.05) biomarkers concentrations. 47Ti,118Sn and 29Si were significantly higher in CC workers (p&lt;0.005). IsoP and TAP were positively associated with 29Si (both p&lt;0.001), 47Ti (p=0.036,p=0.003), 52Cr (p=0.048,p=0.003) and 118Sn (p=0.047,p=0.022). The ongoing analyses will assess the potential mediation role of OS and metal biomarkers. Occupational exposure to NMs can represent an underestimated hazard for people handling NMs products, increasing OS and potentially beginning pathological processes. Although the health significance of such findings needs to be further elucidated, the assessment of metals in urine may represent a useful tool for estimating the body burden of NMs long-term exposure.
147 Human Lung Organoids Predict Response to Carbon-Based Nanomaterials and Model Pulmonary Fibrosis
Authors: Issa Rahaf , Lozano Neus , Kostarelos Kostas , Vranic Sandra 
Published: May 2023

Abstract
Advances in in-vitro culture systems have stimulated an interest in more reliable testing approaches that predict nanomaterial toxicity. Lung organoids are one example, and display functions consistent with their in-vivo counterparts. Organoids have been used in a variety of applications, but studies have yet to interrogate their suitability for nanomaterial testing. Here, we report the step-wise development of multilineage lung organoids, and validate their potential as tools for predicting pulmonary toxicity of carbon-based nanomaterials. After 50-days of differentiation, the lung organoids exhibited the six major proximal (goblet/basal/club/ciliated) and distal (AECI/II) epithelial cell types of the adult lung. Using microinjection, we developed an exposure model to exploit the airspace-like lumen of the organoids for cargo delivery. We compared the impact of small nanometric (50-950nm, sGO) and large micrometric (4-41µm, lGO) graphene oxide sheets, with multi-walled carbon nanotubes (1-20µm, MWCNT) on lung organoids after 1/7/28d exposure. Consistent with in-vivo data, sGO and lGO exhibited a transient interaction with the alveolar epithelium, and did not induce any histoarchitectural changes indicative of fibrosis. Organoids did however produce 2.5-fold more mucins in response to lGO than sGO exposure, suggesting that a thicker mucin barrier is required to prevent lGO-induced damage. In contrast, MWCNT caused detrimental effects on organoid architecture. Its persistent interaction with the alveolar epithelium led to a pro-fibrotic phenotype, where MWCNT caused AECII to undergo epithelial-mesenchymal transition. With further development, our model may reduce the need for rodent inhalation studies in the assessment of lung toxicity.
156 Nitrogen-Doped Multi-Walled Carbon Nanotubes show Attenuated Pathogenicity in a Mouse Model of Pleural Exposure
Authors: Zacarias-Cabeza Joaquin , Chernova Tatyana , Craxton Andrew , Sun Xiao-Ming , Galavotti Sara , Beier Sina , Self Emily L , Greaves Peter , Poland Craig A , Tsuruoka Shuji , Porter Dale W , Willis Anne E , MacFarlane Marion 
Published: May 2023

Abstract
Engineered carbon nanotubes (CNT) are currently used in many industrial products. Multi-walled carbon nanotubes (MWCNT) exhibit unique physicochemical properties and due to their low density and small size are easily aerosolized, making workplace exposure a potential risk to human health. MWCNT are similar to Asbestos in terms of their high aspect-ratio and thus may pose an asbestos-like inhalation hazard, including sporadic pleural Mesothelioma. Mitsui-7 MWCNT (MWCNT-7) have been classified by IARC as a Group 2B carcinogen. Importantly, physicochemically-altered MWCNT synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their pathogenicity in the pleura is unknown. Using a mouse model of direct injection into the pleural cavity, we compared the molecular changes that occur at the mesothelium over 20-months following injection with an occupationally-relevant dose of MWCNT-7, MWCNT-ND, Asbestos or carbon black. When compared to Asbestos or MWCNT-7, mice injected with MWCNT-ND did not develop respiratory symptoms. In contrast, in cell lines established from pleural effusions from MWCNT-7 or Asbestos-exposed mice with pre-neoplastic lesions or tumours, Whole-Exome-Sequencing and RNASeq revealed common molecular changes in both lesions and tumours. This identified genes involved in driving progression of pleural inflammatory lesions to Mesothelioma, whereas pre-neoplastic lesion-derived cell lines allow dissection of the hazard mechanism of pathogenic fibres at the molecular level early in disease development and thus may help predict genotoxic potency in exposed human populations.
Our data demonstrate that physicochemical alteration of MWCNT (e.g. synthesis with nitrogen) attenuates pathogenicity and may offer an alternative for use in industrial applications.
37 Functional Requirements to Develop a new Risk Assessment Model for Exposure to Biological Agents
Authors: Colomo Carlota Alejandre , Marchand Geneviève , van der Haar Rudolf , Antiller Cristina Bercero , Viegas Carla , Houba Remko , Zilaout Hicham , Heussen Henri 
Published: May 2023

Abstract
Within Occupational Risk Prevention, the assessment of risks due to exposure to biological agents has received little attention compared to risks such as those arising from chemicals. This was the case until the impact of the COVID-19 pandemic highlighted the importance of health effects related to exposure to biological agents in the work environment. However, the tools for hazard inventory, risk assessment, and implementation of control measures for biological agents are scarce. There are many reasons that make it challenging for OHS professionals to assess the exposure to biological agents such as, little knowledge on the biological agents potentially present in the different economic activities, their effects on health, the lack of standardized methods for quantitative sampling or the lack of reference values available for most biological agents. Different qualitative risk assessment tools for biological agents have been developed over the last decades. Some examples are the Simplified Evaluation of the INSST (Spain), the Biogaval-Neo of the INVASSAT (Spain), the Bioaerosol Tool of the IRSST (Canada) or the RIE Method of the NKAL (The Netherlands). These tools differ from each other in terms of their scope and the parameters used to determine risk and were compared in order to better understand their limitations and applicability. After the comparison was carried out some additional specific parameters have been proposed as essential for the development of this new model. The proposed improvements could be implemented in the development of a new qualitative biological risk assessment model in the Stoffenmanager® tool.
55 Investigating the co-Exposure of Micro(nano)Plastics and Indoor/Outdoor Particulate Matter Using an Alveolar BarrierIn Vitro Model
Authors: Wright Olivia Whittle , Meldrum Kirsty , Doak Shareen H , Wright Stephanie , Clift Martin J D 
Published: May 2023

Abstract
The impact of micro-, nanoplastics (MNPs) and particulate matter (PM) upon human health are escalating concerns worldwide. MNPs released from surgical face masks, and PM from ambient air pollution, can both be inhaled and consequently have potentially significant negative impacts upon human health, particularly on our lung epithelial cell structure and function. Currently, the impact of the realistic co-exposure of these samples is unknown. Therefore, the purpose of this study was to determine the potential inhaled hazardous health effects of the co-exposure of MNPs and ambient (indoor and outdoor) air PM. Using an advanced in vitro testing model combined with a specific mechanistic toxicology approach, it is hypothesised that the co-exposure approach will elucidate important information regarding the differential toxicology of ambient (indoor and outdoor) air PM. The in vitro system will consist of alveolar epithelial type-II cells (-NCI-H441) combined with differentiated monocytes (dTHP-1), cultured at the relevant in vivo ratio and at the air-liquid interface. Cell cultures will be exposed for both 4 and 24hrs to MNP (commercially available polypropylene (PP) and blue face mask extracted PP), PM (NIST 2584 and NIST 1649a respectively) and then subsequent MNP+PM (both NIST 2584 and NIST 1649a respectively) via aerosol (VITROCELL Cloud12), using alternative dosimetry patterns. The biochemical endpoints of cytotoxicity, oxidative stress, (pro-)inflammatory response and genotoxicity, will then be assessed to provide the basis for future global analytical techniques to examine the currently unknown human hazard of inhaled MNPs (+/- PM).
57 Particles in Outdoor Air: are they all Equal?
Authors: Miller Mark , Clift Martin , Harrison Roy , Kelly Frank , Doutsi Artemis , Mitsakou Christina , Earl Naomi , Exley Karen , Gowers Alison 
Published: May 2023

Abstract
Statement from the Committee on the Medical Effects of Air Pollutants (COMEAP) on the differential toxicity of particulate matter according to source or constituents
Particulate matter in outdoor air comes from a wide range of different sources and contains many different chemical components. Understanding which of these sources and components are particularly harmful would help to focus policies and interventions to reduce impacts on health. COMEAP recently (July 2022) published an updated statement on this topic, drawing on recent reviews of the available evidence. It noted that particulate matter, and constituents of particulate matter, associated with combustion and road traffic have received the most research attention. However, there was insufficient coherence in the epidemiological evidence to conclude that these sources of particulate matter play a significantly greater role in the health effects of particulate air pollution than other sources or constituents. A comprehensive review of the evidence reveals that toxicity has been attributed to a wide variety of constituents and sources, possibly acting by a number of different mechanisms. However, the complexity of sources, sizes and chemical composition of particulate matter makes it extremely difficult to identify which characteristics of particles might make them less harmful or more toxic than others. Future research assessing the influence of chemical composition of particulate matter should offer greater insights into toxicity. But, at present, PM2.5 (the mass concentration of fine particulate matter in air) remains the most suitable metric for evaluating health impacts and regulating particulate air pollution.
2 Humanising Nanotoxicology Testing: Moving Towards Animal-free Approaches for Hazard Assessment of Nanomaterials
Authors: Pokorski Pawel , Stone Vicki , Murphy Fiona 
Published: May 2023

Abstract
The vast array of nanomaterials (NMs) under development raises ethical concerns over the reliance and extent of animal usage in the hazard assessment of substances. Grouping which allows read-across of data from NMs predicted to pose similar hazard could provide justification for waiving of in vivo tests. The GRACIOUS Framework has defined Integrated Approaches to Testing and Assessment (IATAs) to guide the generation of data to support grouping. Each IATA is underpinned by a tiered testing strategy promoting the use of acellular and in vitro assays, (Tier 1-2), which are predictive of in vivo mechanisms of toxicity. Tier 3 in vivo studies are only required to confirm grouping or fill specific gaps. Adopting the IATA approach allows the effective triage of vast number of NMs prioritized for in vivo hazard assessment, thus reducing overall animal testing. However, many of the methods recommended at Tier 1-2 are reliant on the use of animal-derived materials and reagents. The information gathered at early Tiers therefore cannot be considered animal-free unless adaptions are made to standard in vitro protocols to replace all animal-derived reagents. The objective of this study was to review the GRACIOUS Inhalation IATA and identify where animal-free options could be selected when designing experimental hazard studies. The replacement of animal-derived reagents with human alternatives was trialed in multiple Tier 1 assays using a CuO NM as a case study material. This proof-of-concept study informs the suitability of animal-free methods for NM hazard assessment and demonstrates only minor adaptions may be required.
66 Sugarcane Ash and Sugarcane Ash-Derived Silica Nanoparticles Alter Mitochondrial Function and Metabolic Activity in Human Proximal Tubular Kidney Cells
Authors: Stem Arthur , Rogers Keegan , Roncal-Jimenez Carlos , Johnson Richard , Brown Jared 
Published: May 2023

Abstract
Multiple epidemics of chronic kidney disease of an unknown etiology (CKDu), primarily in young healthy agricultural workers, have emerged in agricultural communities around the world. We have hypothesized that the harvest and burning of sugarcane leading to inhalation of sugarcane ash may contribute to development of CKDu. Sugarcane stalks consist of ~80% amorphous silica and we have demonstrated that following burning of sugarcane, nano-sized silica particles (~200nm) are generated. To determine what effect such exposures have on kidney cells, a human proximal convoluted tubule (PCT) cell line (HK-2) was subjected to treatments ranging in concentration from 0.025µg/mL to 25µg/mL of sugarcane ash, desilicated sugarcane ash, sugarcane ash-derived silica nanoparticles (SAD SiNPs), or manufactured pristine 200nm silica nanoparticles. Following 6 to 48 hours of exposure, mitochondrial activity and viability were found to be significantly reduced when exposed to SAD particles at concentrations 2.5µg/mL or higher. Oxygen consumption rate (OCR) and pH were investigated with a Seahorse XF Analyzer, revealing significant changes to cellular metabolism across treatments as early as 6 hours following exposure. While most treatments slightly increased respiration, SAD SiNPs were found to inhibit mitochondrial function, reduce ATP generation, increase reliance on glycolysis, and reduce glycolytic reserve. Metabolomic analysis following 24 hours of exposure found several cellular energetics pathways (e.g., fatty acid metabolism, glycolysis, and TCA cycle) significantly altered across ash-based treatments. Such changes indicate that exposure to sugarcane ash and its derivatives can promote mitochondrial dysfunction and disrupt metabolic activity of human PCT cells.
68 On the Role of Chemical Identity over the size of Model Ultrafine Particles Driven (geno)-Toxicity
Authors: Pantzke Jana , Das Anusmita , Zimmermann Elias J , Offer Svenja , Jeong Seongho , Delaval Mathilde N , Schnelle-Kreis Jürgen , Sklorz Martin , Bucchianico Sebastiano Di , Zimmermann Ralf 
Published: May 2023

Abstract
Especially through the release from anthropogenic sources, there is growing concern about human exposure to ultrafine particulate matter (UFP). Inhalation of UFP is associated with respiratory diseases such as asthma, pulmonary fibrosis and lung cancer, but their mechanisms of action are still vastly unknown. In this study we aimed to address the question whether the physical characteristics of UFP contribute most to their toxicity or whether the particles primarily act as carriers of toxic chemicals. For this scope, two distinct UFP aerosols with low or high content of semi-volatile organic compounds (SVOC) but comparable sizes were produced by a combustion aerosol standard soot generator and investigated regarding their acute (geno)-toxic potential in a cell model consisting of alveolar epithelial cells, macrophages, and fibroblasts at the air-liquid interface. Low SVOC UFP induced an increased cytotoxicity accompanied by a reduced cell number of epithelial cells and a decreased metabolic activity of fibroblasts. Furthermore, an increased intracellular release of reactive oxygen species (ROS) was observed after low SVOC UFP treatment, which resulted in a depletion of intracellular glutathione. The increased ROS release could be causative for the observed secondary genotoxicity in fibroblasts exclusively detected after exposure to low organic content UFP. High SVOC UFP did not impact cell viability, but an increased DNA damage could be detected in epithelial cells. All in all, UFP with low organic content seem to induce a stronger acute cytotoxic and oxidative stress response in epithelial cells, which might cause secondary effects in fibroblasts.
70 Inhalation Exposure of Copper Particles - Quantitative Differentiation Between Copper Oxides and Metallic Copper
Authors: Bluemlein Katharina , Schirmer Thorben , Licht Oliver , Schuchardt Sven 
Published: May 2023

Abstract
Inhalation exposure to copper and its inorganic compounds can occur in various industrial sectors such as ore mining, production of electrical equipment etc. Toxic effects of copper and its oxides have been shown to be attributed to i. particle size and ii. dissolution/release of copper ions. The latter being dependend on the chemical composition of the copper particle and its size. Hence, in the context of occupational inhalation exposure to those compounds emphasis should not only be directed towards particle size but also to the copper species. We have developed an ICP-MS based method that allows quantitative distinction between copper oxides (CuxO) and metallic copper (mCu) upon sampling on mixed-cellulose ester (MCE) membrane filters. This approach is based on the different dissolution properties of CuxO and mCu in dilute acid. Systematic assessment of the approach in regard to filter load and extraction time have been conducted and successfully applied to field samples.
84 Bugs and our Airways: Successful Development and Evaluation of a School Outreach Project
Authors: Marczylo Emma , Macchiarulo Sameirah , Bowsher Rachel , Goode Emma-Jane 
Published: May 2023

Abstract
Increased awareness of air pollution and its potential health impacts has led to many national and international ‘clean air’ initiatives. However, what do we really mean by ‘clean air’? While the recent pandemic has highlighted the consequences of infectious disease, many remain less aware of the impact biological airborne particles (so-called bioaerosols) can have on non-communicable diseases such as allergy and asthma. This project aimed to improve children’s understanding of bioaerosols and their positive and negative associations with airway and lung health. We trialled three sessions over a three-week period in primary school children aged 10-11 years to discuss bioaerosols and health within an engaging and educational framework, with the added benefit of promoting STEM and inspiring them to think about the range of careers within environmental science and public health. Sessions included a mixture of presentations and interactive activities. At the end of each session, we conducted evaluation sessions with both students and teachers. Children engaged well with the subject material, enthusiastically contributed to discussions and activities, and provided useful feedback for further improvements. They particularly enjoyed the hands-on activities and demonstrations, and the teacher commented that the sessions complemented the curriculum by linking new concepts to existing knowledge. This project encouraged two-way engagement between multidisciplinary researchers, teachers and children to develop engaging, fun and educational activities. This will provide a legacy of resources and expertise to expand across the wider schools’ networks, building excellent public engagement capacity and capability.
91 Development of Methods for Exposure- and Risk Assessment of Graphene
Authors: Storsjö Tobias , Sun Jinhua , Tinnerberg Håkan , Farbrot Anne 
Published: May 2023

Abstract
The purpose of this work is to evaluate the Organic carbon/elemental carbon technique as a method to quantify and identify the exposure of graphene and its derivatives, the aim being to propose a standardized occupational exposure measurements method for graphene. Graphene is a 2D-material consisting primarily of elemental carbon, and has many useful properties such as flexibility, elasticity, and conductivity among others. Graphene could therefore become a material used in many occupational fields in the future, and as of today, no optimal measuring technique for occupational exposure exists. The readily available techniques are either nonspecific or nonquantitative. An OC/EC-instrument can quantitively determine the amount of and distinguish between two different types of carbon, organic and elemental carbon. OC/EC could therefore be a possible measuring method used to quantitively determine occupational exposure to graphene. Preliminary test of the method has shown that it is possible to determine the amount of graphene on a quartz filter using the technique. Early results have also shown that it is possible to pinpoint which type of graphene that has been analysed between, graphene oxide, reduced graphene oxide and graphene. The technique needs optimization, but early results indicates that the technique could be a fast and efficient monitoring technique.