Particle-stabilized emulsions offer a strategy for forming mechanically robust microcapsules based on coassembly of silica nanoparticles, polyelectrolytes, and surfactants at oil-water interfaces. Such systems have complicated distributions of inorganic colloidal solids, surfactants, solvents, and ions that influence their compositions and structures over multiple length scales, which have been challenging to characterize and establish. To do so, silica-polyelectrolyte microcapsules were prepared with nearly monodisperse dimensions in the submicron range from water-in-oil (W/O) emulsions that were stabilized by a combination of nonionic surfactants, anionic silica nanoparticles, and cationic polyelectrolyte chains. Nonionic surfactants were used to establish oil as the continuous phase, while silica-polyelectrolyte complexes, self-assembled at the oil-water interfaces, prevented coalescence between droplets and provided mechanical elasticity. Particle charge measurements show that the surface charge density of the silica nanoparticles can be controlled by adjusting the pH conditions or by substituting aluminate ions at their surfaces. These promoted strong electrostatic and hydrogen-bonding interactions with the cationic polyelectrolyte and nonionic surfactant species, direct atomic-scale evidence of which is provided by solid-state two-dimensional (2D) 29Si{1H} NMR. For nanoparticles with higher surface charge densities, strong electrostatic interactions are the basis for particle coassembly with cationic polyelectrolyte species, and the resulting silica-polyelectrolyte complexes adsorb at the oil-water interface, as revealed by cryogenic electron microscopy. Relative to larger spherical nanoparticles, the elongated nanoparticles exhibit more extensive hydrogen bonding with polar organic moieties, which contributes to polyelectrolyte bridging between particles with lower densities of surface negative charges, consistent with interfacial rheology analyses. In addition to interfacial compositions and conditions, noncovalent polyelectrolyte-silica interactions, governed by nanoparticle surface compositions, charge density, and surface area, can be adjusted to control the macroscopic mechanical properties of the microcapsule interfaces.

BACKGROUND:The Safe and Sustainable by Design (SSbD) concept facilitates the design of safer and more sustainable chemicals and materials and is a crucial approach towards reaching the goals set out in the European Green Deal. It is critical that suitable guidance is provided on how to use new approach methodologies (NAMs) to fill hazard data gaps for nanomaterials (NMs) to facilitate SSbD decisions. Here, we showcase a nano-specific in vitro SSbD case study. The five colloidal silica nanoforms (SiO2-NFs) under investigation in this study are surface modified with varying amounts of glycerolpropyl-organosilane groups. In this study, we use a simple yet comprehensive in vitro test battery along with thorough particle characterization to investigate the effect of surface silanization on in vitro toxicity to inform SSbD decisions. RESULTS:Cytotoxic, pro-inflammatory and oxidative stress responses in A549, dTHP-1, and BEAS-2B cells after exposure to SiO2-NFs submerged and at the air-liquid interface (ALI) decreased with increasing silane surface modification. None of the SiO2-NFs showed surface reactivity or haemolytic potential. Deposition assessment using inductively coupled plasma - optical emission spectrometry (ICP-OES) revealed that increasing silane surface modification decreased particle settling. The two SiO2-NFs with the highest amount of surface silanization did not reach the cells in a submerged exposure setting, and they were therefore only tested at the ALI. Identical dose-response curves were observed for both the submerged testing and testing at the ALI for the SiO2-NFs without and with low/intermediate surface functionalization, again showing a decrease in effects with increasing surface functionalization. CONCLUSION:We show that in vitro toxicity assays provide valuable information for SSbD decision making. In vitro cytotoxic, pro-inflammatory and oxidative stress responses can be reduced with increasing surface silane functionalization. The reduced deposition efficiency with increasing silane functionalization, however, highlights that thorough characterization of particle behaviour in cell culture medium should always be performed for SSbD hazard testing. The amount of silane required to reduce toxicity is important information for the future production of safer SiO2-NFs and nano-enabled products. Exposure, functionality, and sustainability remain to be investigated to draw full SSbD conclusions.

We present formulations of dispersions based on beeswax for consolidating encaustic paintings, which use beeswax as a binder and are applied on a canvas or wooden substrate. Commercial natural and synthetic adhesives are used for consolidation of such paintings, but they often have problems due to the consolidant material not being compatible with the original painting. The dispersions were prepared by combining Pickering beeswax emulsions stabilized by cellulose nanocrystals (CNC) with hydrophobically modified ethylhydroxyethylcellulose (EHM). The drop size of the emulsion varied with the beeswax content and the emulsion drops displayed inclusions of water droplets. These inclusions led upon drying to films that showed a hollow micromorphology, which enhanced the water evaporation, giving high breathability. The dispersions comprising beeswax, CNC and EHM were stable over time and the viscosity was governed by the amount of EHM in the formulation. The dried films were very hydrophobic with a water contact angle of about 130°. The emulsion-based formulations were tested on encaustic painting mock-ups made on wood substrate to examine their adhesive strength and water resistance. The formulations achieved better performance than commercial products used as consolidants for encaustic paintings. The beeswax-based compositions, which contain only green components and free of volatile organic compounds, offer an interesting platform for consolidation in the field of cultural heritage.

To facilitate Safe-and-Sustainable-by-Design (SSbD), the HARMLESS project developed a practical SSbD approach and SSbD Decision Support System (DSS) for advanced materials. The HARMLESS SSbD approach and SSbD-DSS are in alignment with the EU-recommended SSbD framework and methods. The HARMLESS SSbD approach recommends New Approach Methodologies (NAMs) tailored to advanced materials and the innovation stage of the material under development. The approach follows a flexible stage-gate model with three innovation stages: 1) Ideation & Business Case Phase, 2) Lab Phase, and 3) Pilot Phase. The HARMLESS SSbD-DSS guides designers through a workflow starting with the Advanced Material Earliest Assessment (AMEA) tool. AMEA contains three questions enabling categorization and subsequently advice on design principles. A second tool, named Warning flags, Design Advice, Screening Priorities (WASP), consists of 12 questions to identify early warning flags and provide design and assessment advice. A third tool, named Alternative SSbD Design Inspector (ASDI), provides guidance on descriptors to measure in the Lab Phase for informed decision making on the most optimal SSbD version. By adapting the data and resource requirements to each innovation stage, the SSbD-DSS facilitates practical implementation of SSbD, supporting the user to find a transparent balance between safety, sustainability, and performance.

In the context of the EU Chemicals Strategy for Sustainability toward a Toxic-free Environment, and in the aim to facilitate Safe-and-Sustainable-by-Design (SSbD) development of new materials and products, the EU-funded project HARMLESS built a Decision Support System (DSS) to support innovators in SSbD assessments of products at early design stages. The HARMLESS DSS is tailored to enable Advanced Materials (AdMa) screening, using a combination of New Approach Methodologies and guided by Integrated Approaches to Testing and Assessment. Three online tools for SSbD screenings are developed and tested on case study materials, namely: Advanced Materials Earliest Assessment; Warning flags, design Advice, Screening Priorities; and Alternative SSbD Inspector. The following case studies are assessed: oxide perovskites for automotive catalysts, imogolites for agricultural solutions, aerogel mats for facade insulation, and colloidal silica for paint formulations. The case study materials are provided by both large and small enterprises, they represent diverse industry sectors and different stages in the value chain. Results show the DSS ability to guide innovators in developing SSbD AdMa, by facilitating the assessment of most SSbD dimensions and visualizing the results in a comprehensive, yet detailed way, enabling their own balancing of SSbD benefits and trade-offs.

Advanced Materials (AdMa) play a crucial role for numerous strategies that address global challenges. They are being developed fast, making it increasingly challenging for regulation to keep pace with innovation. Existing frameworks, which are either not designed for AdMa or lack adequate filtering to identify AdMa of high concern, do not (yet) effectively support regulatory preparedness. The HARMLESS Early Warning System (EWS), in contrast, is a practically applicable tool for screening plenty of materials in a reasonable time. It is organized in two tiers, each underpinned by a specific methodology and facilitated by a dedicated online tool. The initial Tier 0 categorizes the materials using the Advanced Materials Earliest Assessment (AMEA) tool. Tier 1 first screens materials asking only 15 questions and is ideal for data-poor materials at early innovation stages. These questions cover issues related to human/ environmental exposure and hazard, sustainability and applicability of existing regulations. In a more elaborated version, experimental testing based on New Approach Methodologies (NAMs) is suggested. As outcome, the user is provided with 1) material-related concerns, 2) prioritization of AdMa and 3) recommendations for (regulatory) follow-up actions. Data from two industrial case studies is presented to demonstrate the applicability of the HARMLESS EWS.

AMEA supports innovators in the earliest phases of material development. AMEA provides design rules and recommends more testing requirements and/or specific methods depending on the positioning of the material in categories.

Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.

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

Hypothesis: Preparation of suspensions of nanoparticles (>1 wt%) coated with a polyelectrolyte multilayers is a challenging task because of the risk of flocculation when a polyelectrolyte is added to a suspension of oppositely charged nanoparticles. This situation can be avoided if the charge density of the polymers and particles is controlled during mixing so as to separate mixing and adsorption events. Experiments: The cationic polyethylenimine (PEI) and the anionic carboxymethylcellulose (CMC) were used as weak polyelectrolytes. Polyelectrolyte multilayers build-up was conducted by reducing the charge of one of the components during the addition of the next component. Charge density was controlled by tuning pH. Analysis of the suspension of coated nanoparticles was done by means of dynamic light scattering, electrophoresis and small angle x-ray scattering measurements, while quartz crystal microbalance was used to study the build-up process on flat silica surfaces. Findings: Charge density, controlled through pH, can be used as a tool to avoid flocculation during layerby-layer deposition of polyelectrolytes on 20 nm silica particles at high concentration (-40 wt%). When added to silica at pH 3, PEI did not induce flocculation. Adsorption was triggered by raising the pH to 11, pH at which CMC could be added. The pH was then lowered to 3. The process was repeated, and up to five polyelectrolyte layers were deposited on concentrated silica nanoparticles while inducing minimal aggregation.

Colloidal silica nanomaterials as adsorbents for aquatic pollutants.

Nanoforms (NFs) of a substance may be distinguished from one another through differences in their physicochemical properties. When registering nanoforms of a substance for assessment under the EU REACH framework, five basic descriptors are required for their identification: composition, surface chemistry, size, specific surface area and shape. To make the risk assessment of similar NFs efficient, a number of grouping frameworks have been proposed, which often require assessment of similarity on individual physicochemical properties as part of the group justification. Similarity assessment requires an understanding of the achievable accuracy of the available methods. It must be demonstrated that measured differences between NFs are greater than the achievable accuracy of the method, to have confidence that the measured differences are indeed real. To estimate the achievable accuracy of a method, we assess the reproducibility of six analytical techniques routinely used to measure these five basic descriptors of nanoforms: inductively coupled plasma mass spectrometry (ICP-MS), Thermogravimetric analysis (TGA), Electrophoretic light scattering (ELS), Brunauer-Emmett-Teller (BET) specific surface area and transmission and scanning electron microscopy (TEM and SEM). Assessment was performed on representative test materials to evaluate the reproducibility of methods on single NFs of substances. The achievable accuracy was defined as the relative standard deviation of reproducibility (RSDR) for each method. Well established methods such as ICP-MS quantification of metal impurities, BET measurements of specific surface area, TEM and SEM for size and shape and ELS for surface potential and isoelectric point, all performed well, with low RSDR, generally between 5 and 20%, with maximal fold differences usually <1.5 fold between laboratories. Applications of technologies such as TGA for measuring water content and putative organic impurities, additives or surface treatments (through loss on ignition), which have a lower technology readiness level, demonstrated poorer reproducibility, but still within 5-fold differences. The expected achievable accuracy of ICP-MS may be estimated for untested analytes using established relationships between concentration and reproducibility, but this is not yet the case for TGA measurements of loss on ignition or water content. The results here demonstrate an approach to estimate the achievable accuracy of a method that should be employed when interpreting differences between NFs on individual physicochemical properties.

Different nanoforms (NF) of the same substance each need to be registered under REACH, but similarities in physiological interaction -among them biodissolution- can justify read-across within a group of NFs, thereby reducing the need to perform animal studies. Here we focused on the endpoint of inhalation toxicity and explored how differences in physical parameters of 17 NFs of silica, and organic and inorganic pigments impact dissolution rates, half-times, and transformation under both pH 7.4 lung lining conditions and pH 4.5 lysosomal conditions. We benchmarked our observations against well-known TiO2, BaSO4 and ZnO nanomaterials, representing very slow, partial and quick dissolution respectively. By automated image evaluation, structural transformations were observed for dissolution rates in the order of 0.1 to 10 ng/cm(2)/h, but did not provide additional decision criteria on the similarity of NFs. Dissolution half-times spanned nearly five orders of magnitude, mostly dictated by the substance and simulant fluid, but modulated up to ten-fold by the subtle differences between NFs. Physiological time scales and benchmark materials help to frame the biologically relevant range, proposed as 1 h to 1 y. NFs of ZnO, Ag, SiO2, BaSO4 were in this range. We proposed numerical rules of pairwise similarity within a group, of which the worst case NF would be further assessed by in vivo inhalation studies. These rules divided the colloidal silica NFs into two separate candidate groups, one with Al-doping, one without. Shape or silane surface treatment were less important. The dissolution halftimes of many organic and inorganic pigment NFs were longer than the biologically relevant range, such that dissolution behavior is not an obstacle for their groupings.

The paper industry is an important sector annually consuming kilotons of nanoforms and non-nanoforms of fillers and pigments. Fillers accelerate the rate of drying (less energy needed) and product cost (increasing the load of low-cost fillers). The plastic industry is another use sector, where coloristic pigments can be in nanoform, and many food containers are made of plastic. Use of paper to wrap both wet and dry food is consumer practice, but not always intended by producers. Here we compare the release behavior of different nano-enabled products (NEPs) by changing a) nanoform (NF) characteristics, b) NF load, c) the nano-enabled product (NEP) matrix, and d) food simulants. The ranking of these factors enables an assessment of food contact by concepts of analogy, specifically via the similarities of the rate and form of release in food during contact. Three types of matrices were used: Paper, plastic ((Polylactic Acid (PLA), Polyamide (PA6), and Polyurethane (PU)), and a paint formulation. Two nanoforms each of SiO2, Fe2O3, Cu-Phthalocyanine were incorporated, additionally to the conventional form of CaCO3 that is always contained in paper to reduce cellulose consumption. Tests were guided by the European Regulation EC 1935/2004 and EU 10/2011. No evidence of particle release was observed: the qualitative similarity (the form of release) was high regarding the food contact of all NEPs with embedded NFs. Quantitative similarity of releases depended primarily on the NEP matrix, as this controls the penetration of the simulant fluid into the NEP. The solubility of the NF and impurities in the simulant fluid was the second decisive factor, as dissolution of the NF inside the NEP is the main mechanism of release. This led to complete removal of CaCO3 in acidic medium, whereas Fe and Si signals remained in the paper, consistent with the low release rates in an ionic form. In our set of 16 NEPs, only one NEP showed a dependence on the REACH NF descriptors (substance, size, shape, surface treatment, crystallinity, impurities), specifically attributed to differences in soluble impurities, whereas for all others the substance of the nanoform was sufficient to predict a similarity of food contact release, without influences of size, shape, surface treatment and crystallinity.

Accidental or open waste burning and incineration of nano-enabled products (NEPs) might lead to the release of incidental aerosols in the nano size range into the environment resulting in harmful effects on humans. We have investigated combustion-generated aerosol release during accidental burning for several real-life NEPs such as paints with silica (SiO2) and spruce wood panels containing SiO2 and Fe2O3 nanomaterials (NMs), paper with SiO2 and Fe2O3 NMs and polymeric composites with CuPhthtalocyanine NMs in poly lactic acid (PLA), polyamide 6 (PA6) and thermoplastic pol-urethane (TPU) matrices. Chemical compositions, aerosols number emission factors (nefs) and concentrations of the signature elements of the NMs of the combustion-generated aerosols were investigated. In addition, the residual ash was analyzed. The outcomes of this study shed light on how NM and matrix types influenced the properties of the released aerosols. Based on our results it was established that the combustion-generated aerosols were composed of transformed NMs with modified physical-chemical characteristics compared to the pristine NMs. In addition to aerosols with transformed NMs, there were also particles due to incomplete combustion of the matrix. Types of the pristine NMs and matrices affected the characteristics of the released aerosols. Since the effect of the aerosols is related to the inhaled aerosol number concentration, the nef is an important parameter. Our results showed that the nefs in the size range of 5.6 to 560 nm depended strongly on the type of combusted NEP, which indicated that the NEPs could be categorized according to their potential to release aerosols in this size range when they were burnt. The generated release data facilitate the assessment of human and environmental exposure and the associated risk assessment of combustion-generated aerosols from NEPs.

Polyethyleneimine (PEI) is a common polymer used in many industrial applications and in research, especially in surface chemistry. It is available in a wide range of molecular weights and different degrees of branching. It is classified as linear or branched and sometimes the term hyperbranched is also used. This description, however, is quite rough, which limits the possibility to correlate the structure of the PEI to its properties. The aim of this study is to provide analytical tools to characterize the polymer at a level of detail not normally provided by the supplier of PEI. To this end, five commercially available polyethyleneimines were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and nuclear magnetic resonance spectroscopy to gain insight into the structure and the functional groups present in the polymers. Quantitative C-13 NMR analysis turned out to be particularly useful, revealing the degree of branching of the polymer based on the ratio of primary, secondary, and tertiary amino groups.

Colloidal assembly of silica (nano)particles is a powerful method to design functional materials across multiple length scales. Although this method has enabled the fabrication of a wide range of silica‐based materials, attempts to design and synthesize porous materials with a high level of tuneability and control over pore dimensions have remained relatively unsuccessful. Here, the colloidal assembly of silica nanoparticles into mesoporous silica microspheres (MSMs) is reported using a discrete set of silica sols within the confinement of a water‐in‐oil emulsion system. By studying the independent manipulation of different assembly parameters during the sol–gel process, a design strategy is outlined to synthesize MSMs with excellent reproducibility and independent control over pore size and overall porosity, which does not require additional ageing or post‐treatment steps to reach pore sizes as large as 50 nm. The strategy presented here can provide the necessary tools for the microstructural design of the next generation of tailor‐made silica microspheres for use in separation applications and beyond.

The multiscale pore structure of mesoporous silica microspheres plays an important role for tuning mass transfer kinetics in technological applications such as liquid chromatography. While local analysis of a pore network in such materials has been previously achieved, multiscale quantification of microspheres down to the nanometer scale pore level is still lacking. Here we demonstrate for the first time, by combining low convergence angle scanning transmission electron microscopy tomography (LC-STEM tomography) with image analysis and lattice Boltzmann simulations, that the multiscale pore network of commercial mesoporous silica microspheres can be quantified. This includes comparing the local tortuosity and intraparticle diffusion coefficients between different regions within the same microsphere. The results, spanning more than two orders of magnitude between nanostructures and entire object, are in good agreement with bulk characterization techniques such as nitrogen gas physisorption and add valuable local information for tuning mass transfer behavior (in liquid chromatography or catalysis) on the single microsphere level.

The conservation of textiles is a challenge due to the often fast degradation that results from the acidity combined with a complex structure that requires remediation actions to be conducted at several length scales. Nanomaterials have lately been used for various purposes in the conservation of cultural heritage. The advantage with these materials is their high efficiency combined with a great control. Here, we provide an overview of the latest developments in terms of nanomaterials-based alternatives, namely inorganic nanoparticles and nanocellulose, to conventional methods for the strengthening and deacidification of cellulose-based materials. Then, using the case of iron-tannate dyed cotton, we show that conservation can only be addressed if the mechanical strengthening is preceded by a deacidification step. We used CaCO3 nanoparticles to neutralize the acidity, while the stabilisation was addressed by a combination of nanocellulose, and silica nanoparticles, to truly tackle the complexity of the hierarchical nature of cotton textiles. Silica nanoparticles enabled strengthening at the fibre scale by covering the fibre surface, while the nanocellulose acted at bigger length scales. The evaluation of the applied treatments, before and after an accelerated ageing, was assessed by tensile testing, the fibre structure by SEM and the apparent colour changes by colourimetric measurements.