For several decades, we have been able to control and “observe” matter at the atomic level. However, manipulation at this level also entails risks that can originate from particles measuring just a few nanometres in size. The discussion began with criticism of the nanotechnology itself but ultimately ended with the definition of a new discipline within toxicology: nanotoxicology. For 30 years, scientists around the world have been grappling with questions surrounding the toxicology of nanomaterials.

In times of social change, science has a special responsibility to provide evidence-based results to foster the generation of solutions for the pressing challenges of today, such as climate change or digitalization. To spread knowledge on scientific findings, science communication is inevitable. It intensifies the dialog with the public, objectifies current debates, and provides information about the challenges and opportunities of new scientific developments. For more than 20 years, research has been ongoing worldwide on the safety and risks of nanomaterials. In this paper, the authors describe their experiences with science communication, using the knowledge database www.nanoobjects.info as an example. Already in 2009, the online knowledge base www.nanoobjects.info was established to share scientific results on the safety of nanomaterials with the public in a value-neutral manner. In 2020, advanced materials were added to this information platform to provide understanding and awareness of toxicological data on these materials as early as possible. These knowledge base materials are currently providing safety-relevant information on 30 advanced materials, including nanomaterials, with regards to human health and environmental impact.

In this perspective, the authors give their view on the developments and experiences on communicating on (nano)materials safety. We would like to share our experiences with the scientific community in order to make them useful for future communication activities. We present the long-term work of the science communication projects DaNa, DaNa2.0 and DaNa4.0, running from 2009 to 2023. Starting in the early 2000s with the beginnings of nanotechnology research, communication on the safety of nanomaterials with the public was still very new and faced the projects with many challenges. Today, science communication is indispensable for the dissemination of scientific findings and a fact-based approach like the DaNa “Knowledge Base Materials” creates a trustworthy dialogue with the public. This long-term project series has made a significant contribution to communication on the safety of nanomaterials, perhaps even the largest among publicly funded project series worldwide.

Transparent and reliable communication of the safety of advanced and nanomaterials is an issue that has become increasingly important in recent times. The German initiative DaNa got involved in this topic at an early stage. It is running the Knowledge Base Materials, a web-based information platform on nanomaterials ( www.nanoobjects.info ) for more than 10 years, which is constantly being expanded. Recently, due to emerging developments in materials science, the focus has been expanded from nanomaterials to the variant-rich group of advanced materials, softening the restriction to particles below the 100 m size limit in one dimension to include larger particles with more complex composition. For the Knowledge Base Materials, this broader scope presents a challenge for science communication. In this paper, the authors describe the selection of materials, the workflow, and the quality control that was performed to provide reliable knowledge about the safety of advanced materials to humans and the environment.

Titanium dioxide is a ubiquitous white material found in a diverse range of products from foods to sunscreens, as a pigment and thickener, amongst other uses. Titanium dioxide has been considered no longer safe for use in foods (nano and microparticles of E171) by the European Food Safety Authority (EFSA) due to concerns over genotoxicity. There are however, conflicting opinions regarding the safety of Titanium dioxide. In an attempt to clarify the situation, a comprehensive weight of evidence (WoE) assessment of the genotoxicity of titanium dioxide based on the available data was performed. A total of 192 datasets for endpoints and test systems considered the most relevant for identifying mutagenic and carcinogenic potential were reviewed and discussed for both reliability and relevance (by weight of evidence) and in the context of whether the physico-chemical properties of the particles had been characterised. The view of an independent panel of experts was that, of the 192 datasets identified, only 34 met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity. Of these, 10 were positive (i.e. reported evidence that titanium dioxide was genotoxic), all of which were from studies of DNA strand breakage (comet assay) or chromosome damage (micronucleus or chromosome aberration assays). All the positive findings were associated with high cytotoxicity, oxidative stress, inflammation, apoptosis, necrosis, or combinations of these. Considering that DNA and chromosome breakage can be secondary to physiological stress, it is highly likely that the observed genotoxic effects of titanium dioxide, including those with nanoparticles, are secondary to physiological stress. Consistent with this finding, there were no positive results from the in vitro and in vivo gene mutation studies evaluated, although it should be noted that to definitively conclude a lack of mutagenicity, more robust in vitro and in vivo gene mutation studies would be useful. Existing evidence does not therefore support a direct DNA damaging mechanism for titanium dioxide (nano and other forms).

Hazard assessment is the first step in nanomaterial risk assessment. The overall number of studies on the biological effects of nanomaterials or innovative materials is steadily increasing and is above 40,000. Several databases have been established to make the amount of data manageable, but these are often highly specialized or can be used only by experts. This paper describes a new database which uses an already existing data collection of about 35,000 publications. The collection from the first phase between the years 2000 and 2013 contains about 11,000 articles and this number has been reduced by specific selection criteria. The resulting publications have been evaluated for their quality regarding the toxicological content and the experimental data have been extracted. In addition to material properties, the most important value to be extracted is the no-observed-adverse-effect-level (NOAEL) for in vivo and the no-observed-effect-concentration (NOEC) for in vitro studies. The correlation of the NOAEL/NOEC values with the nanomaterial properties and the investigated endpoints has been tested in projects such as the OECD-AOP project, where the available data for inflammatory responses have been analysed. In addition, special attention was paid to titanium dioxide particles and this example is used to show with searches for in vitro and in vivo experiments on possible lung toxicity what a typical result of a database query can look like. In this review, an emerging database is described that contains valuable information for nanomaterial hazard estimation and should aid in the progress of nanosafety research.

Background Nanomaterials are suspected of causing health problems, as published studies on nanotoxicology indicate. On the other hand, some of these materials, such as nanostructured pyrogenic and precipitated synthetic amorphous silica (SAS) and silica gel, have been used for decades without safety concerns in industrial, commercial, and consumer applications. However, in addition to many in vivo and in vitro studies that have failed to demonstrate the intrinsic toxicity of SAS, articles periodically emerge, in which biological effects of concern have been described. Even though most of these studies do not meet high-quality standards and do not always use equivalent test materials or standardized test systems, the results often trigger substance re-evaluation. To put the results into perspective, an extensive literature study was carried out and an example of amorphous silica will be used to try to unravel the reliability from the unreliable results. Methods A systematic search of studies on nanotoxicological effects has been performed covering the years 2013 to 2018. The identified studies have been evaluated for their quality regarding material and method details, and the data have been curated and put into a data collection. This review deals only with investigations on amorphous silica. Results Of 18,162 publications 1,217 have been selected with direct reference to experiments with synthetically produced amorphous silica materials. The assessment of these studies based on defined criteria leads to a further reduction to 316 studies, which have been included in this systematic review. Screening for quality with well-defined quantitative criteria following the GUIDE nano concept reveals only 27.3% has acceptable quality. Overall, the in vitro and in vivo data showed low or no toxicity of amorphous silica. The data shown do not support the hypothesis of dependency of biological effects on the primary particle size of the tested materials. Conclusion This review demonstrates the relatively low quality of most studies published on nanotoxicological issues in the case of amorphous silica. Moreover, mechanistic studies are often passed off or considered toxicological studies. In general, standardized methods or the Organization for Economic Cooperation and Development (OECD) guidelines are rarely used for toxicological experiments. As a result, the significance of the published data is usually weak and must be reevaluated carefully before using them for regulatory purposes.

Significant advances have been made in the development of Adverse Outcome Pathways (AOPs) over the last decade, mainly focused on the toxicity mechanisms of chemicals. These AOPs, although relevant to manufactured nanomaterials (MNs), do not currently capture the reported roles of size-associated properties of MNs on toxicity. Moreover, some AOs of relevance to airborne exposures to MNs such as lung inflammation and fibrosis shown in animal studies may not be targeted in routine regulatory decision making. The primary objective of the present study was to establish an approach to advance the development of AOPs of relevance to MNs using existing, publicly available, nanotoxicology literature. A systematic methodology was created for curating, organizing and applying the available literature for identifying key events (KEs). Using a case study approach, the study applied the available literature to build the biological plausibility for 'tissue injury', a KE of regulatory relevance to MNs. The results of the analysis reveal the various endpoints, assays and specific biological markers used for assessing and reporting tissue injury. The study elaborates on the limitations and opportunities of the current nanotoxicology literature and provides recommendations for the future reporting of nanotoxicology results that will expedite not only the development of AOPs for MNs but also aid in application of existing data for decision making.

Faster, cheaper, sensitive, and mechanisms-based animal alternatives are needed to address the safety assessment needs of the growing number of nanomaterials (NM) and their sophisticated property variants. Specifically, strategies that help identify and prioritize alternative schemes involving individual test models, toxicity endpoints, and assays for the assessment of adverse outcomes, as well as strategies that enable validation and refinement of these schemes for the regulatory acceptance are needed. In this review, two strategies 1) the current nanotoxicology literature review and 2) the adverse outcome pathways (AOPs) framework, a systematic process that allows the assembly of available mechanistic information concerning a toxicological response in a simple modular format, are presented. The review highlights 1) the most frequently assessed and reported ad hoc in vivo and in vitro toxicity measurements in the literature, 2) various AOPs of relevance to inhalation toxicity of NM that are presently under development, and 3) their applicability in identifying key events of toxicity for targeted in vitro assay development. Finally, using an existing AOP for lung fibrosis, the specific combinations of cell types, exposure and test systems, and assays that are experimentally supported and thus, can be used for assessing NM-induced lung fibrosis, are proposed.

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTNanosafety: Where Are We Now and Where Must We Go?Harald KrugHarald KrugNanoCase GmbH, 9032 Engelburg, SwitzerlandMore by Harald Krug and Annette KraegelohAnnette KraegelohINM-Leibniz-Institute for New Materials, D-66123 Saarbruecken, GermanyMore by Annette KraegelohCite this: Chem. Res. Toxicol. 2019, 32, 4, 535Publication Date (Web):April 15, 2019Publication History Published online15 April 2019Published inissue 15 April 2019https://pubs.acs.org/doi/10.1021/acs.chemrestox.9b00083https://doi.org/10.1021/acs.chemrestox.9b00083editorialACS PublicationsCopyright © 2019 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views975Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (173 KB) Get e-AlertscloseSUBJECTS:Nanomaterials Get e-Alerts

Nanomaterials have found their way in our everyday lives via numerous market applications ranging from electronics to the health care system. They offer great innovative potential and are assumed to be beneficial to mankind and the environment. However, consumers, journalists, or regulators often miss reliable and understandable information on nanomaterials and their applications. Communication of scientific facts with the public is an ambitious task as complex issues need to be simplified whilst ensuring scientific correctness. Due to the multidisciplinary nature of nanotechnology, communication on safety aspects is particularly challenging. The DaNa2.0 project (data and knowledge on nanomaterials) is addressing these challenges by collecting and evaluating scientific results. Alongside, a criteria checklist for quality evaluation and management of scientific publications with mandatory and desirable criteria has been developed to ensure a thorough and comprehensive assessment. These evaluated research findings are presented in a worldwide unique knowledge base, correlating material properties and applications, tailored to interested citizens, stakeholders and scientists. The DaNa2.0 platform www.nanoobjects.info offers easy-to-understand, up-to-date and quality-approved information on the 26 most widely used nanomaterials together with FAQs and cross-cutting topics like Nanomedicine. DaNa2.0 is a national project funded by the German Federal Ministry of Education and Research (FKZ 03X0131).

One of the challenges in using in vitro data to understand the potential risks of engineered nanomaterials (ENMs) is that results often differ or are even contradictory among studies. While it is recognized that numerous factors can influence results produced by nanobioassays, there has not yet been a consistently used conceptual framework to identify key sources of variability in these assays. In this paper, we use cause-and-effect analysis to systematically describe sources of variability in four key in vitro nanobioassays: the 2',7'-dichlorofluorescein assay, an enzyme-linked immunosorbent assay for measuring interleukin-8, a flow cytometry assay (Annexin V/propidium iodide), and the Comet assay. These assays measure end points that can occur in cells impacted by ENMs through oxidative stress, a principle mechanism for ENM toxicity. The results from this analysis identify control measurements to test for potential artifacts or biases that could occur during conduct of these assays with ENMs. Cause-and-effect analysis also reveals additional measurements that could be performed either in preliminary experiments or each time the assay is run to increase confidence in the assay results and their reproducibility within and among laboratories. The approach applied here with these four assays can be used to support the development of a broad range of nanobioassays.

Adverse outcome pathways (AOPs) represent a sequence of key events (KEs) between a molecular initiating event (MIE) and an adverse outcome (AO) and span many levels of biological organization including molecular, cellular, tissue, organ, organism, and population. AOPs link specific biological observations with AOs. AOPs are not specific to individual chemicals; however, they were traditionally developed for chemicals. The objective of the present study is to advance the identification of KEs using existing nanotoxicology literature as part of an Organisation for Economic Cooperation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN) project aiming to support the future development of AOPs relevant for Manufactured Nanomaterials (MNs). A database of 11,000 nanotoxicology studies published between 2000 and 2013 was assessed for the types of MNs investigated and for the assays, endpoints and toxicity effects presented. Since tissue inflammation is one of the consistently observed and reported effects following MN exposure, the large database was processed to select those studies reporting specifically on inflammation to identify inflammation-associated KEs. This exercise resulted in 191 publications describing ~60 different endpoints for 45 different MNs, which were used in identification of MN-induced KEs and selection of single or multiple KEs that are relevant to AOs of regulatory interest. This report summarises the key findings of the study describing the various KEs identified, and the reported assays and specific measurements used to assess the KEs. The report also describes a single KE ‘Tissue Injury’, selected by the process for further development in a case study as part of the OECD WPMN project to show its relevance to MN-induced AOs, and in turn, to future MN risk assessment. Finally, the challenges and limitations of the existing nanotoxicology literature for the development of MN-relevant AOPs are highlighted.

Abstract Research on engineered nanomaterials (ENM) has progressed rapidly from the very early stages of studying their unique, size-dependent physicochemical properties and commercial exploration to the development of products that influence our everyday lives. We have previously reviewed various methods for synthesis, surface functionalization, and analytical characterization of ENM in a publication titled ‘Engineered Nanomaterials: Preparation, Functionalization and Characterization’. In this second, inter-linked document, we first provide an overview of important applications of ENM in products relevant to human healthcare and consumer goods, such as food, textiles, and cosmetics. We then highlight the challenges for the design and development of new ENM for bio-applications, particularly in the rapidly developing nanomedicine sector. The second part of this document is dedicated to nanotoxicology studies of ENM in consumer products. We describe the various biological targets where toxicity may occur, summarize the four nanotoxicology principles, and discuss the need for careful consideration of the biodistribution, degradation, and elimination routes of nanosized materials before they can be safely used. Finally, we review expert opinions on the risk, regulation, and ethical aspects of using engineered nanomaterials in applications that may have direct or indirect impact on human health or our environment.

Green chemistry, also called sustainable chemistry, is an area of chemistry and chemical engineering focused on the designing of products and processes that minimize the use and generation of hazardous substances. Whereas environmental chemistry focuses on the effects of polluting chemicals on nature, green chemistry focuses on the environmental impact of chemistry, including technological approaches to preventing pollution and reducing consumption of nonrenewable resources. The overarching goals of green chemistry—namely, more resource-efficient and inherently safer design of molecules, materials, products, and processes—can be pursued in a wide range of contexts. In the present book, twelve typical literatures about green chemistry published on international authoritative journals were selected to introduce the worldwide newest progress, which contains reviews or original researches on green synthesis, sustainable development, renewable feedstock, biodegradation, multi-component green synthesis and green cycle, etc. We hope this book can demonstrate advances in green chemistry as well as give references to the researchers, students and other related people.

For this Editorial, we, the guest editors, performed a brief review with the aim of setting the framework for the Special issue on the “Environmental Impacts of Nanomaterials” [...]