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Fifteen years of airborne particulates in vitro toxicology in Milano: Lessons and perspectives learned

Longhin, Eleonora Marte; Mantecca, Paride; Gualtieri, Maurizio

Air pollution is one of the world’s leading environmental causes of death. The epidemiological relationship between outdoor air pollution and the onset of health diseases associated with death is now well established. Relevant toxicological proofs are now dissecting the molecular processes that cause inflammation, reactive species generation, and DNA damage. In addition, new data are pointing out the role of airborne particulates in the modulation of genes and microRNAs potentially involved in the onset of human diseases. In the present review we collect the relevant findings on airborne particulates of one of the biggest hot spots of air pollution in Europe (i.e., the Po Valley), in the largest urban area of this region, Milan. The different aerodynamic fractions are discussed separately with a specific focus on fine and ultrafine particles that are now the main focus of several studies. Results are compared with more recent international findings. Possible future perspectives of research are proposed to create a new discussion among scientists working on the toxicological effects of airborne particles.

MDPI

2020

NanoSolveIT Project: Driving nanoinformatics research to develop innovative and integrated tools for in silico nanosafety assessment

Afantitis, Antreas; Melagraki, Georgia; Isigonis, Panagiotis; Tsoumanis, Andreas; Varsou, Dimitra Danai; Valsami-Jones, Eugenia; Papadiamantis, Anastasios; Ellis, Laura-Jayne; Sarimveis, Haralambos; Doganis, Philip; Karatzas, Pantelis; Tsiros, Periklis; Liampa, Irene; Lobaskin, Vladimir; Greco, Dario; Serra, Angela; Kinaret, Pia Anneli Sofia; Saarimaki, Laura Aliisa; Grafström, Roland; Kohonen, Pekka; Nymark, Penny; Willighagen, Egon; Puzyn, Tomasz; Rybinska-Fryca, Anna; Lyubartsev, Alexander; Jensen, Keld Alstrup; Brandenburg, Gerit; Lofts, Stephen; Svendsen, Claus; Harrison, Samuel; Maier, Dieter; Tamm, Kaido; Jänes, Jaak; Sikk, Lauri; Dusinska, Maria; Longhin, Eleonora Marte; Rundén-Pran, Elise; Mariussen, Espen; El Yamani, Naouale; Unger, Wolfgang; Radnik, Jörg; Tropsha, Alexander; Cohen, Yoram; Leszcynski, Jerzy; Hendren, Christine Ogilvie; Wiesner, Mark; Winkler, David; Suzuki, Noriyuki; Yoon, Tae Hyun; Choi, Jang-Sik; Sanabria, Natasha; Gulumian, Mary; Lynch, Iseult

Nanotechnology has enabled the discovery of a multitude of novel materials exhibiting unique physicochemical (PChem) properties compared to their bulk analogues. These properties have led to a rapidly increasing range of commercial applications; this, however, may come at a cost, if an association to long-term health and environmental risks is discovered or even just perceived. Many nanomaterials (NMs) have not yet had their potential adverse biological effects fully assessed, due to costs and time constraints associated with the experimental assessment, frequently involving animals. Here, the available NM libraries are analyzed for their suitability for integration with novel nanoinformatics approaches and for the development of NM specific Integrated Approaches to Testing and Assessment (IATA) for human and environmental risk assessment, all within the NanoSolveIT cloud-platform. These established and well-characterized NM libraries (e.g. NanoMILE, NanoSolutions, NANoREG, NanoFASE, caLIBRAte, NanoTEST and the Nanomaterial Registry (>2000 NMs)) contain physicochemical characterization data as well as data for several relevant biological endpoints, assessed in part using harmonized Organisation for Economic Co-operation and Development (OECD) methods and test guidelines. Integration of such extensive NM information sources with the latest nanoinformatics methods will allow NanoSolveIT to model the relationships between NM structure (morphology), properties and their adverse effects and to predict the effects of other NMs for which less data is available. The project specifically addresses the needs of regulatory agencies and industry to effectively and rapidly evaluate the exposure, NM hazard and risk from nanomaterials and nano-enabled products, enabling implementation of computational ‘safe-by-design’ approaches to facilitate NM commercialization.

Elsevier

2020

The way forward for assessing the human health safety of cosmetics in the EU - Workshop proceedings

Rogiers, Vera; Benfenati, Emilio; Bernauer, Ulrike; Bodin, Laurent; Carmichael, Paul; Chaudhry, Qasim; Coenraads, Pieter Jan; Cronin, Mark T.D.; Dent, Matthew; Dusinska, Maria; Ellison, Corie; Ezendam, Janine; Gaffet, Eric; Galli, Corrado Lodovico; Goebel, Carsten; Granum, Berit; Hollnagel, Heli Miriam; Kern, Petra S.; Kosemund-Meynen, Kirstin; Ouedraogo, Gladys; Panteri, Eirini; Rousselle, Christophe; Stepnik, Maciej; Vanhaecke, Tamara; von Goetz, Natalie; Worth, Andrew

Elsevier

2020

Nanomaterial grouping: Existing approaches and future recommendations

Giusti, Anna; Atluri, Rambabu; Tsekovska, Rositsa; Gajewicz, Agnieszka; Apostolova, Margarita; Battistelli, Chiara L.; Bleeker, Eric; Bossa, Cecilia; Bouillard, Jaques; Dusinska, Maria; Gómez-Fernández, Paloma; Grafström, Roland; Gromelski, Maciej; Handzhiyski, Yordan; Jacobsen, Nicklas Raun; Jantunen, Paula; Jensen, Keld Alstrup; Mech, Agnieszka; Navas, José Maria; Nymark, Penny; Oomen, Agnes G.; Puzyn, Tomasz; Rasmussen, Kirsten; Riebeling, Christian; Rodriguez-LLopis, Isabel; Sabella, Stefania; Sintes, Juan Riego; Suarez-Merino, Blanca; Tanasescu, Speranta; Wallin, Håkan; Haase, Andrea

The physico-chemical properties of manufactured nanomaterials (NMs) can be fine-tuned to obtain different functionalities addressing the needs of specific industrial applications. The physico-chemical properties of NMs also drive their biological interactions. Accordingly, each NM requires an adequate physico-chemical characterization and potentially an extensive and time-consuming (eco)toxicological assessment, depending on regulatory requirements. Grouping and read-across approaches, which have already been established for chemicals in general, are based on similarity between substances and can be used to fill data gaps without performing additional testing. Available data on “source” chemicals are thus used to predict the fate, toxicokinetics and/or (eco)toxicity of structurally similar “target” chemical(s). For NMs similar approaches are only beginning to emerge and several challenges remain, including the identification of the most relevant physico-chemical properties for supporting the claim of similarity. In general, NMs require additional parameters for a proper physico-chemical description. Furthermore, some parameters change during a NM's life cycle, suggesting that also the toxicological profile may change.

This paper compares existing concepts for NM grouping, considering their underlying basic principles and criteria as well as their applicability for regulatory and other purposes. Perspectives and recommendations based on experiences obtained during the EU Horizon 2020 project NanoReg2 are presented. These include, for instance, the importance of harmonized data storage systems, the application of harmonized scoring systems for comparing biological responses, and the use of high-throughput and other screening approaches. We also include references to other ongoing EU projects addressing some of these challenges.

Elsevier

2019

The comet assay in animal models: From bugs to whales ? (Part 2 Vertebrates)

Gajski, Goran; Žegura, Bojana; Ladeira, Carina; Novak, Matjaž; Srámková, Monika; Pourrut, Bertrand; Del Bo', Cristian; Milić, Mirta; Gutzkow, Kristine Bjerve; Costa, Solange; Dusinska, Maria; Brunborg, Gunnar; Collins, Andrew Richard

Elsevier

2019

The concept of essential use for determining when uses of PFASs can be phased out

Cousins, Ian T.; Goldenman, Gretta; Herzke, Dorte; Lohmann, Rainer; Miller, Mark; Ng, Carla A.; Patton, Sharyle; Scheringer, Martin; Trier, Xenia; Vierke, Lena; Wang, Zhanyun; DeWitt, Jamie

Because of the extreme persistence of per- and polyfluoroalkyl substances (PFASs) and their associated risks, the Madrid Statement argues for stopping their use where they are deemed not essential or when safer alternatives exist. To determine when uses of PFASs have an essential function in modern society, and when they do not, is not an easy task. Here, we: (1) develop the concept of “essential use” based on an existing approach described in the Montreal Protocol, (2) apply the concept to various uses of PFASs to determine the feasibility of elimination or substitution of PFASs in each use category, and (3) outline the challenges for phasing out uses of PFASs in society. In brief, we developed three distinct categories to describe the different levels of essentiality of individual uses. A phase-out of many uses of PFASs can be implemented because they are not necessary for the betterment of society in terms of health and safety, or because functional alternatives are currently available that can be substituted into these products or applications. Some specific uses of PFASs would be considered essential because they provide for vital functions and are currently without established alternatives. However, this essentiality should not be considered as permanent; rather, constant efforts are needed to search for alternatives. We provide a description of several ongoing uses of PFASs and discuss whether these uses are essential or non-essential according to the three essentiality categories. It is not possible to describe each use case of PFASs in detail in this single article. For follow-up work, we suggest further refining the assessment of the use cases of PFASs covered here, where necessary, and expanding the application of this concept to all other uses of PFASs. The concept of essential use can also be applied in the management of other chemicals, or groups of chemicals, of concern.

Royal Society of Chemistry (RSC)

2019

Technical recommendations to perform the alkaline standard and enzyme-modified comet assay in human biomonitoring studies

Azqueta, Amaya; Muruzabal, Damian; Boutet-Robinet, Elisa; Milic, Mirta; Dusinska, Maria; Brunborg, Gunnar; Møller, Peter; Collins, Andrew R.

2019

The comet assay in animal models: From bugs to whales – (Part 1 Invertebrates)

Gajski, Goran; Žegura, Bojana; Ladeira, Carina; Pourrut, Bertrand; Del Bo, Cristian; Novak, Matjaž; Srámková, Monika; Milić, Mirta; Gutzkow, Kristine Bjerve; Costa, Solange; Dusinska, Maria; Brunborg, Gunnar; Collins, Andrew Richard

Elsevier

2019

Insights into possibilities for grouping and read-across for nanomaterials in EU chemicals legislation

Mech, A.; Rasmussen, K.; Jantunen, P.; Aicher, L.; Alessandrelli, M.; Bernauer, U.; Bleeker, E. A. J.; Bouillard, J.; Di Prospero Fanghella, P.; Draisci, R.; Dusinska, Maria; Encheva, G.; Flament, G.; Haase, A.; Handzhiyski, Y.; Herzberg, F.; Huwyler, J.; Jacobsen, N.R.; Jeliazkov, V.; Jeliazkova, N.; Nymark, P.; Grafström, R.; Oomen, A. G.; Polci, M. L.; Riebeling, C.; Sandström, J.; Shivachev, B.; Stateva, S.; Tanasescu, S.; Tsekovska, R.; Wallin, Håkan; Wilks, M. F.; Zellmer, S.; Apostolova, M. D.

This paper presents a comprehensive review of European Union (EU) legislation addressing the safety of chemical substances, and possibilities within each piece of legislation for applying grouping and read-across approaches for the assessment of nanomaterials (NMs). Hence, this
review considers both the overarching regulation of chemical substances under REACH (Regulation (EC) No 1907/2006 on registration, evaluation, authorization, and restriction of chemicals) and CLP (Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures) and the sector-specific pieces of legislation for cosmetic, plant protection and biocidal products, and legislation addressing food, novel food, and food contact materials. The relevant supporting documents (e.g. guidance documents) regarding each piece of legislation were identified and reviewed, considering the relevant technical and scientific literature. Prospective regulatory needs for implementing grouping in the assessment of NMs were identi-
fied, and the question whether each particular piece of legislation permits the use of grouping and read-across to address information gaps was answered.

Informa Healthcare

2019

Polychlorinated biphenyls (PCBs) as sentinels for the elucidation of Arctic environmental change processes: a comprehensive review combined with ArcRisk project results

Carlsson, Pernilla; Breivik, Knut; Brorström-Lundén, Eva; Cousins, Ian; Christensen, Jesper; Grimalt, Joan O.; Halsall, Crispin; Kallenborn, Roland; Abass, Khaled; Lammel, Gerhard; Munthe, John; MacLeod, Matthew; Odland, Jon Øyvind; Pawlak, Janet; Rautio, Arja; Reiersen, Lars-Otto; Schlabach, Martin; Stemmler, Irene; Wilson, Simon; Wöhrnschimmel, Henry

Polychlorinated biphenyls (PCBs) can be used as chemical sentinels for the assessment of anthropogenic influences on Arctic environmental change. We present an overview of studies on PCBs in the Arctic and combine these with the findings from ArcRisk—a major European Union-funded project aimed at examining the effects of climate change on the transport of contaminants to and their behaviour of in the Arctic—to provide a case study on the behaviour and impact of PCBs over time in the Arctic. PCBs in the Arctic have shown declining trends in the environment over the last few decades. Atmospheric long-range transport from secondary and primary sources is the major input of PCBs to the Arctic region. Modelling of the atmospheric PCB composition and behaviour showed some increases in environmental concentrations in a warmerArctic, but the general decline in
PCB levels is still the most prominent feature. ‘Within-Arctic’ processing of PCBs will be affected by climate change-related processes such as changing wet deposition. These in turn will influence biological exposure and uptake of PCBs. The pan-Arctic rivers draining large Arctic/sub-Arctic catchments provide a significant source of PCBs to the Arctic Ocean, although changes in hydrology/sediment transport combined with a changing marine environment remain areas of uncertainty with regard to PCB fate. Indirect effects of climate change on human exposure, such as a changing diet will influence and possibly reduce PCB
exposure for indigenous peoples. Body burdens of PCBs have declined since the 1980s and are predicted to decline further.

Springer

2018

Applications of low-cost sensing technologies for air quality monitoring and exposure assessment: How far have they gone?

Morawska, Lidia; Thai, Phong K.; Liu, Xiaoting; Asumadu-Sakyi, Akwasi; Ayoko, Godwin; Bartonova, Alena; Bedini, Andrea; Chai, Fahe; Christensen, Bryce; Dunbabin, Matthew; Gao, Jian; Hagler, Gayle S. W.; Jayaratne, Rohan; Kumar, Prashant; Lau, Alexis K. H.; Louie, Peter K. K.; Mazaheri, Mandana; Ning, Zhi; Motta, Nunzio; Mullins, Ben; Rahman, Md Mahmudur; Ristovski, Zoran; Shafiei, Mahnaz; Tjondronegoro, Dian; Westerdahl, Dane; Williams, Ron

Elsevier

2018

A Review of Airborne Particulate Matter Effects on Young Children’s Respiratory Symptoms and Diseases

Liu, Hai-Ying; Dunea, Daniel; Iordache, Stefania; Pohoata, Alin

Exposure to airborne fine particulate matter (PM2.5) carries substantial health risks, particularly for younger children (0–10 years). Epidemiological evidence indicates that children are more susceptible to PM health effects than adults. We conducted a literature review to obtain an overview of existing knowledge regarding the correlation of exposure to short- and long-term PM concentrations with respiratory symptoms and disease in children. A collection of scientific papers and topical reviews were selected in cooperation with two experienced paediatricians. The literature review was performed using the keywords “air pollution”, “particulate matter”, “children’s health” and “respiratory” from 1950 to 2016, searching the databases of Scopus, Google Scholar, Web of Science, and PubMed. The search provided 45,191 studies for consideration. Following the application of eligibility criteria and experts’ best judgment to titles and abstracts, 28 independent studies were deemed relevant for further detailed review and knowledge extraction. The results showed that most studies focused mainly on the effect of short-term exposure in children, and the reported associations were relatively homogeneous amongst the studies. Most of the respiratory diseases observed in outdoor studies were related to changes in lung function and exacerbation of asthma symptoms. Allergic reactions were frequently reported in indoor studies. Asthma exacerbation, severe respiratory symptoms and moderate airway obstruction on spirometry were also observed in children due to various sources of indoor pollution in households and schools. Mixed indoor and outdoor studies indicate frequent occurrence of wheezing and deterioration of lung function. There is good evidence of the adverse effect of short-term exposure to PM on children’s respiratory health. In terms of long-term exposure, fine particles (PM0.1–PM2.5) represent a higher risk factor than coarse particles (PM2.5–PM10). Additional research is required to better understand the heterogeneous sources and the association of PM and adverse children’s health outcomes. We recommend long-term cooperation between air quality specialists, paediatricians, epidemiologists, and parents in order to improve the knowledge of PM effects on young children’s respiratory health.

MDPI

2018

Soil contamination and sources of phthalates and its health risk in China: A review

Lü, Huixiong; Mo, Ce-Hui; Zhao, Hai-Ming; Xiang, Lei; Katsoyiannis, Athanasios A.; Li, Yan-Wen; Cai, Quan-Ying; Wong, Ming-Hung

Elsevier

2018

The comet assay applied to cells of the eye

Azqueta, Amaya; Rundén-Pran, Elise; Elje, Elisabeth; Nicolaissen, Bjørn; Haug, Kristiane; Smeringaiova, Ingrida; Jirsova, Katerina; Collins, Andrew Richard

Oxford University Press

2018

Refining in vitro models for nanomaterial exposure to cells and tissues

Guggenheim, Emily J.; Milani, Silvia; Röttgermann, Peter J. F.; Dusinska, Maria; Saout, Christelle; Salvati, Anna; Rädler, Joachim O.; Lynch, Iseult

Elsevier

2018

What is the effect of phasing out long-chain per- and polyfluoroalkyl substances on the concentrations of perfluoroalkyl acids and their precursors in the environment? A systematic review

Land, Magnus; de Wit, Cynthia A.; Bignert, Anders; Cousins, Ian T.; Herzke, Dorte; Johansson, Jana H.; Martin, Jonathan W.

There is a concern that continued emissions of man-made per- and polyfluoroalkyl substances (PFASs) may cause environmental and human health effects. Now widespread in human populations and in the environment, several PFASs are also present in remote regions of the world, but the environmental transport and fate of PFASs are not well understood. Phasing out the manufacture of some types of PFASs started in 2000 and further regulatory and voluntary actions have followed. The objective of this review is to understand the effects of these actions on global scale PFAS concentrations.

BioMed Central (BMC)

2018

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