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Due to the analytical challenges of detecting and quantifying nanoparticles in seawater, the data on distributions of NPs in the marine environment is limited to qualitative studies or by ensemble measurements subject to various analytical artifacts. Single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) allows determination of individual inorganic NPs at environmentally relevant concentrations, yet only few studies have been conducted on selected elements in surface sea water. Here, a sequential multi-element screening method was developed and implemented to provide a first survey of the horizontal and vertical distributions of inorganic nanoparticles and trace elements in a pristine Norwegian fjord prospect for submarine tailings deposition. Statistical control of false-positive detections while minimizing the size detection limit was ensured using a novel raw signal processing. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) gave confirmative and qualitative information regarding particle morphology and composition. Following SP-ICP-MS screening for particles of 16 elements, particulate Al, Fe, Mn, Pb, Si and Ti were found and determined to mass concentrations in ng/L of 1–399, 1–412, below limit of detection (8 particles per liter. Total metals concentrations were at least an order of magnitude higher, at concentrations in μg/L of 1–12 for Al, 2–13 for Fe, 0.3–11 Mn, 0.02–0.5 for Pb, 46 to 318 Si and 0.04–0.4 for Ti. A strong depth dependence was observed for both trace elements and particles with concentrations increasing with depth. Our results provide a baseline for the fjord and new data on environmental levels of both total metals and metal containing nanoparticles including the vertical and horizontal distribution of natural nanoparticles.

Molybdenum disulphide (MoS2) is a constituent of many products. To protect humans, it is important to know at what air concentrations it becomes toxic. For this, we tested MoS2 particles by nose-only inhalation in mice. Exposures were set to 13, 50 and 150 mg MoS2/m3 (=8, 30 and 90 mg Mo/m3), corresponding to Low, Mid and High exposure. The duration was 30 min/day, 5 days/week for 3 weeks. Molybdenum lung-deposition levels were estimated based on aerosol particle size distribution measurements, and empirically determined with inductively coupled plasma-mass spectrometry (ICP-MS). Toxicological endpoints were body weight gain, respiratory function, pulmonary inflammation, histopathology, and genotoxicity (comet assay). Acellular reactive oxygen species (ROS) production was also determined. The aerosolised MoS2 powder had a mean aerodynamic diameter of 800 nm, and a specific surface area of 8.96 m2/g. Alveolar deposition of MoS2 in lung was estimated at 7, 27 and 79 µg/mouse and measured as 35, 101 and 171 µg/mouse for Low, Mid and High exposure, respectively. Body weight gain was lower than in controls at Mid and High exposure. The tidal volume was decreased with Low and Mid exposure on day 15. Increased genotoxicity was seen in bronchoalveolar lavage (BAL) fluid cells at Mid and High exposures. ROS production was substantially lower than for carbon black nanoparticles used as bench-mark, when normalised by mass. Yet if ROS of MoS2 was normalised by surface area, it was similar to that of carbon black, suggesting that a ROS contribution to the observed genotoxicity cannot be ruled out. In conclusion, effects on body weight gain and genotoxicity indicated that Low exposure (13 mg MoS2/m3, corresponding to 0.8 mg/m3 for an 8-hour working day) was a No Observed Adverse Effect Concentration (NOAEC,) while effects on respiratory function suggested this level as a Lowest Observed Adverse Effect Concentration (LOAEC). Molybdenum disulphide (MoS2) is a constituent of many products. To protect humans, it is important to know at what air concentrations it becomes toxic. For this, we tested MoS2 particles by nose-only inhalation in mice. Exposures were set to 13, 50 and 150 mg MoS2/m3 (=8, 30 and 90 mg Mo/m3), corresponding to Low, Mid and High exposure. The duration was 30 min/day, 5 days/week for 3 weeks. Molybdenum lung-deposition levels were estimated based on aerosol particle size distribution measurements, and empirically determined with inductively coupled plasma-mass spectrometry (ICP-MS). Toxicological endpoints were body weight gain, respiratory function, pulmonary inflammation, histopathology, and genotoxicity (comet assay). Acellular reactive oxygen species (ROS) production was also determined. The aerosolised MoS2 powder had a mean aerodynamic diameter of 800 nm, and a specific surface area of 8.96 m2/g. Alveolar deposition of MoS2 in lung was estimated at 7, 27 and 79 µg/mouse and measured as 35, 101 and 171 µg/mouse for Low, Mid and High exposure, respectively. Body weight gain was lower than in controls at Mid and High exposure. The tidal volume was decreased with Low and Mid exposure on day 15. Increased genotoxicity was seen in bronchoalveolar lavage (BAL) fluid cells at Mid and High exposures. ROS production was substantially lower than for carbon black nanoparticles used as bench-mark, when normalised by mass. Yet if ROS of MoS2 was normalised by surface area, it was similar to that of carbon black, suggesting that a ROS contribution to the observed genotoxicity cannot be ruled out. In conclusion, effects on body weight gain and genotoxicity indicated that Low exposure (13 mg MoS2/m3, corresponding to 0.8 mg/m3 for an 8-hour working day) was a No Observed Adverse Effect Concentration (NOAEC,) while effects on respiratory function suggested this level as a Lowest Observed Adverse Effect Concentration (LOAEC).

Some implantable medical devices contain silver. We aimed to assess at what amount implanted silver becomes toxic. Silver was elevated in bodily fluids and tissues surrounding silver-containing implants. Silver released from implants also distributes to blood and other tissues; there is evidence to suggest silver can pass the blood-brain-barrier. Silver can be deposited as nano-sized particles in various tissues. Such particles, in addition to silver, often contain other elements too, e.g., selenium and sulfur. Silver released from implants seems to stay in the body for long periods (years). Reported excretion pathways following implantation are urinary and fecal ones. Reported toxicological effects were virtually all local reactions surrounding the implants. Argyria is a blue-gray discoloration of the skin due to deposited silver granules. Localized argyria has been described after the implantation of acupuncture needles and silver-coated prostheses, although the presence of silver was tested only for and shown in the former. Other toxicological effects include local tissue reactivity and examples of neurotoxic and vascular effects. We did not include genotoxicity studies in the present publication as we recently evaluated silver to be genotoxic. Carcinogenicity studies were absent. We conclude that local toxicity of implanted silver can be foreseen in some situations.

While the exact health risks associated with nanoplastics are currently the focus of intense research, there is no doubt that humans are exposed to nanoplastics and that food could be a major source of exposure. Nanoplastics are released from plastic materials and articles used during food production, processing, storage, preparation, and serving. They are also likely to enter the food chain via contaminated water, air, and soil. However, very limited exposure data for risk assessment exists so far due to the lack of suitable analytical methods. Nanoplastic detection in food poses a great analytical challenge due to the complexity of plastics and food matrices as well as the small size and expectedly low concentration of the plastic particles. Multidetector field flow fractionation has emerged as a valuable analytical technique for nanoparticle separation over the last decades, and the first studies using the technique for analyzing nanoplastics in complex matrices are emerging. In combination with online detectors and offline analysis, multidetector field flow fractionation is a powerful platform for advanced characterization of nanoplastics in food by reducing sample complexity, which otherwise hampers the full potential of most analytical techniques. The focus of this article is to present the current state of the art of multidetector field flow fractionation for nanoplastic analysis and to discuss future trends and needs aiming at the analysis of nanoplastics in food.

The rate of translocation of ingested nanoparticles (NPs) and how the uptake is affected by a food matrix are key aspects of health risk assessment. In this study, female Sprague Dawley rats (N=4/group) received 0, 1.4, or 13 mg of cerium oxide (CeO2 NM-212) NPs/rat/day by gavage or in a chocolate spread snack 5 days/week for 1 or 2 weeks followed by 2 weeks of recovery. A dose and time-dependent uptake in the liver and spleen of 0.1–0.3 and 0.004–0.005 parts per million (ng/mg) of the total administered dose was found, respectively. There was no statistically significant difference in cerium concentration in the liver or spleen after gavage compared to snack dosing. Microscopy revealed indications of necrotic changes in the liver and decreased cellularity in white pulp in the spleen. The snack provided precise administration and a more human-relevant exposure of NPs and could improve animal welfare as alternative to gavage.

The widespread integration of engineered nanomaterials into consumer and industrial products creates new challenges and requires innovative approaches in terms of design, testing, reliability, and safety of nanotechnology. The aim of this review article is to give an overview of different product groups in which nanomaterials are present and outline their safety aspects for consumers. Here, release of nanomaterials and related analytical challenges and solutions as well as toxicological considerations, such as dose-metrics, are discussed. Additionally, the utilization of engineered nanomaterials as pharmaceuticals or nutraceuticals to deliver and release cargo molecules is covered. Furthermore, critical pathways for human exposure to nanomaterials, namely inhalation and ingestion, are discussed in the context of risk assessment. Analysis of NMs in food, innovative medicine or food contact materials is discussed. Specific focus is on the presence and release of nanomaterials, including whether nanomaterials can migrate from polymer nanocomposites used in food contact materials. With regard to the toxicology and toxicokinetics of nanomaterials, aspects of dose metrics of inhalation toxicity as well as ingestion toxicology and comparison between in vitro and in vivo conclusions are considered. The definition of dose descriptors to be applied in toxicological testing is emphasized. In relation to potential exposure from different products, opportunities arising from the use of advanced analytical techniques in more unique scenarios such as release of nanomaterials from medical devices such as orthopedic implants are addressed. Alongside higher product performance and complexity, further challenges regarding material characterization and safety, as well as acceptance by the general public are expected.

This article reviews the current status of nanotechnology with emphasis on application and related environmental considerations as well as legislation. Application and analysis of nanomaterials in infrastructure (construction, building coatings, and water treatment) is discussed, and in particular nanomaterial release during the lifecycle of these applications. Moreover, possible grouping approaches with regard to ecotoxicological and toxicological properties, and the fate of nanomaterials in the environment are evaluated. In terms of potential exposure, the opportunities that arise from leveraging advances in several key areas, such as water treatment and construction are addressed. Additionally, this review describes challenges with regard to the European Commission’s definition of ‘nanomaterial’. The revised REACH information requirements, intended to enable a comprehensive risk assessment of nanomaterials, are outlined.

In single particle inductively coupled plasma mass spectrometry (spICP-MS), the transport efficiency is fundamental for the correct determination of both particle number concentration and size. In the present study, transport efficiency was systematically determined on three different days with six carefully characterised gold nanoparticle (AuNP) suspensions and in seven European and US expert laboratories using different ICP-MS instruments and spICP-MS software. Both particle size—(TES)—and particle frequency—(TEF)—methods were applied. The resulting transport efficiencies did not deviate much under ideal conditions. The TEF method however systematically resulted in lower transport efficiencies. The extent of this difference (0–300% rel. difference) depended largely on the choice and storage conditions of the nanoparticle suspensions used for the determination. The TES method is recommended when the principal measurement objective is particle size. If the main aim of the measurement is the determination of the particle number concentration, the TEF approach could be preferred as it might better account for particle losses in the sample introduction system.

Dissolution plays an important role on pulmonary toxicity of nanomaterials (NMs). The influence of contextual parameters on the results from dissolution testing needs to be identified to improve the generation of relevant and comparable data. This study investigated how pre-dispersions made in water, low-calcium Gamble's solution, phagolysosomal simulant fluid (PSF), and 0.05% bovine serum albumin (BSA) affected the dissolution of the Al

In this work, we show the potential of single-particle inductively coupled plasma-mass spectrometry (spICP-MS) as a screening technique for detection of inorganic nanoparticles (NPs) that are expected to be present in food. We demonstrate that the spICP-MS/MS method in combination with collision/reaction cell gases and microsecond dwell times offers sensitive and interference-free detection of NPs. We present the steps that have to be considered to correctly assess the presence of NPs in food, for example, setting a suitable threshold for discriminating particle events from the baseline and analyzing a sufficient number of blank samples to minimize false-positive results. We applied the proposed screening approach to the sequential detection of NPs containing 8 selected elements that could be potentially present in 13 different food products. The highest mass concentrations of NPs (in the mg/g range) were found in the samples with food additives which are known to contain a fraction of NPs. The presence of (nano)particles in some of the investigated food samples was also confirmed by scanning electron microscopy analysis. Moreover, for the example of Al-containing NPs in Chinese noodles, we demonstrate that identification of the source of NPs with an unknown composition can be challenging when using only spICP-MS as particle mass concentration and size distribution can only be estimated by assuming a certain particle composition/shape. Other complementary techniques for particle characterization, such as electron microscopy in combination with elemental analysis, are therefore required.

Titanium dioxide is a white colourant authorised as food additive E 171 in the EU, where it is used in a range of alimentary products. As these materials may contain a fraction of particulates with sizes below 100 nm and current EU regulation requires specific labelling of food ingredient to indicate the presence of engineered nanomaterials there is now a need for standardised and validated methods to appropriately size and quantify (nano)particles in food matrices. A single-particle inductively coupled plasma mass spectrometry (spICP-MS) screening method for the determination of the size distribution and concentration of titanium dioxide particles in sugar-coated confectionery and pristine food-grade titanium dioxide was developed. Special emphasis was placed on the sample preparation procedure, crucial to reproducibly disperse the particles before analysis. The transferability of this method was tested in an interlaboratory comparison study among seven experienced European food control and food research laboratories equipped with various ICP-MS instruments and using different software packages. The assessed measurands included the particle mean diameter, the most frequent diameter, the percentage of particles (in number) with a diameter below 100 nm, the particles' number concentration and a number of cumulative particle size distribution parameters (D0, D10, D50, D99.5, D99.8 and D100). The evaluated method's performance characteristics were, the within-laboratory precision, expressed as the relative repeatability standard deviation (RSDr), and the between-laboratory precision, expressed as the relative reproducibility standard deviation (RSDR). Transmission electron microscopy (TEM) was used as a confirmatory technique and served as the basis for bias estimation. The optimisation of the sample preparation step showed that when this protocol was applied to the relatively simple sample food matrices used in this study, bath sonication turned out to be sufficient to reach the highest, achievable degree of dispersed constituent particles. For the pristine material, probe sonication was required. Repeatability and reproducibility were below 10% and 25% respectively for most measurands except for the lower (D0) and the upper (D100) bound of the particle size distribution and the particle number concentration. The broader distribution of the lower and the upper bounds could be attributed to instrument-specific settings/setups (e.g. the timing parameters, the transport efficiency, type of mass-spectrometer) and software-specific data treatment algorithms. Differences in the upper bound were identified as being due to the non-harmonised application of the upper counting limit. Reporting D99.5 or D99.8 instead of the effectively largest particle diameter (D100) excluded isolated large particles and considerably improved the reproducibility. The particle number-concentration was found to be influenced by small differences in the sample preparation procedure. The comparison of these results with those obtained using electron microscopy showed that the mean and median particle diameter was, in all cases, higher when using spICP-MS. The main reason for this was the higher size detection limit for spICP-MS plus the fact that some of the analysed particles remained agglomerated/aggregated after sonication. Single particle ICP-MS is a powerful screening technique, which in many cases provides sufficient evidence to confirm the need to label a food product as containing (engineered) titanium dioxide nanomaterial according to the current EU regulatory requirements. The overall positive outcome of the method performance evaluation and the current lack of alternative standardised procedures, would indicate this method as being a promising candidate for a full validation study., Highlights • Standardised methods for sizing of E171 particles in food matrices are unavailable. • Screening method based on spICP-MS is proposed. • Analytical performance parameters and transferability tested in ILC.

We used triple-quadrupole and high-resolution inductively coupled plasma-mass spectrometry (ICP-MS) in single-particle mode to characterize the food additive E171 (titanium dioxide, TiO2) in chewing gum, chocolate candy, and cake decoration in the same sample extracts. Then, we spiked TiO2 particles (with similar characteristics as E171) to milk as an example of a calcium-rich matrix. The obtained particle size distributions with both techniques were highly similar in terms of shape and median and mean diameters. Median diameters were in the range of 123 to 209 nm and mean diameters from 146 to 223 nm. In addition, they were in agreement with results obtained by scanning electron microscopy and asymmetric flow field-flow fractionation coupled to multi-angle light scattering and ICP-MS. Repeatable determination of number-based particle size distributions was possible with both ICP-MS techniques even in a calcium-rich matrix showing that both instruments were similarly efficient in resolving the Ca interferences. The combination of spICP-MS with microscopy and TiO2 recovery allowed validating the methods and identifying the presence of aggregated/agglomerated particles in one sample. For the TiO2 powder and the two remaining food products, recoveries were higher than 60%. Both instruments are fit for purpose even if the analyses were performed with differences in detector mode, dwell times, and calculation tools. This shows that both techniques may be used as long as operating conditions are optimized and applicability range is defined.

Iron oxides used as food colorants are listed in the European Union with the number E172. However, there are no specifications concerning the fraction of nanoparticles in these pigments. Here, seven E172 products were thoroughly characterized. Samples of all colors were analyzed with a broad spectrum of methods to assess their physico-chemical properties. Small-Angle X-ray Scattering (SAXS), Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), zeta-potential, Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), X-ray diffraction (XRD), Brunauer-Emmett-Teller analysis (BET), Asymmetric Flow Field-Flow Fractionation (AF4) and in vitro cell viability measurements were used. Nanoparticles were detected in all E172 samples by TEM or SAXS measurements. Quantitative results from both methods were comparable. Five pigments were evaluated by TEM, of which four had a size median below 100 nm, while SAXS showed a size median below 100 nm for six evaluated pigments. Therefore, consumers may be exposed to iron oxide nanoparticles through the consumption of food pigments.

Despite considerable efforts, the properties that drive the cytotoxicity of engineered nanomaterials (ENMs) remain poorly understood. Here, the authors inverstigate a panel of 31 ENMs with different core chemistries and a variety of surface modifications using conventional in vitro assays coupled with omics‐based approaches. Cytotoxicity screening and multiplex‐based cytokine profiling reveals a good concordance between primary human monocyte‐derived macrophages and the human monocyte‐like cell line THP‐1. Proteomics analysis following a low‐dose exposure of cells suggests a nonspecific stress response to ENMs, while microarray‐based profiling reveals significant changes in gene expression as a function of both surface modification and core chemistry. Pathway analysis highlights that the ENMs with cationic surfaces that are shown to elicit cytotoxicity downregulated DNA replication and cell cycle responses, while inflammatory responses are upregulated. These findings are validated using cell‐based assays. Notably, certain small, PEGylated ENMs are found to be noncytotoxic yet they induce transcriptional responses reminiscent of viruses. In sum, using a multiparametric approach, it is shown that surface chemistry is a key determinant of cellular responses to ENMs. The data also reveal that cytotoxicity, determined by conventional in vitro assays, does not necessarily correlate with transcriptional effects of ENMs., Supported by the European Commission through the FP7‐NANOSOLUTIONS project (Grant Agreement No. 309329). Burcu Açikgöz, Dokuz Eylül University, Turkey, is acknowledged for assistance with nucleic acid corona experiments through the Erasmus program.

Background Previous studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m3 of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7–12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24). Results At week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFα). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet. Conclusion Exposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.

Background Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black. Results Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15–22 nm, specific surface area: 152–222 m2/g, and count median mobility diameter: 55–103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12–0.60), polycyclic aromatic hydrocarbon content (1–27 μg/mg) and acid-extractable metal content (0.9–16 μg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS. Conclusions We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.

With the extensive use of silver nanoparticles (AgNPs) in various consumer products their potential toxicity is of great concern especially for highly sensitive population groups such as pregnant women and even the developing fetus. To understand if AgNPs are taken up and cross the human placenta, we studied their translocation and accumulation in the human ex vivo placenta perfusion model by single particle ICP-MS (spICP-MS). The impact of different surface modifications on placental transfer was assessed by AgNPs with two different modifications: polyethylene glycol (AgPEG NPs) and sodium carboxylate (AgCOONa NPs). AgNPs and ionic Ag were detected in the fetal circulation in low but not negligible amounts. Slightly higher Ag translocation across the placental barrier for perfusion with AgPEG NPs and higher AgNP accumulation in placental tissue for perfusion with AgCOONa NPs were observed. Since these AgNPs are soluble in water, we tried to distinguish between the translocation of dissolved and particulate Ag. Perfusion with AgNO3 revealed the formation of Ag containing NPs in both circulations over time, of which the amount and their size in the fetal circulation were comparable to those from perfusion experiments with both AgNP types. Although we were not able to clarify whether intact AgNPs and/or Ag precipitates from dissolved Ag cross the placental barrier, our study highlights that uptake of Ag ions and/or dissolution of AgNPs in the tissue followed by re-precipitation in the fetal circulation needs to be considered as an important pathway in studies of AgNP translocation across biological barriers.

Single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS) promises fast and selective determination of nanoparticle size and number concentrations. While several studies on practical applications have been published, data on formal, especially interlaboratory validation of sp-ICP-MS, is sparse. An international interlaboratory study was organized to determine repeatability and reproducibility of the determination of the median particle size and particle number concentration of Ag nanoparticles (AgNPs) in chicken meat. Ten laboratories from the European Union, the USA, and Canada determined particle size and particle number concentration of two chicken meat homogenates spiked with polyvinylpyrrolidone (PVP)-stabilized AgNPs. For the determination of the median particle diameter, repeatability standard deviations of 2 and 5% were determined, and reproducibility standard deviations were 15 and 25%, respectively. The equivalent median diameter itself was approximately 60% larger than the diameter of the particles in the spiking solution. Determination of the particle number concentration was significantly less precise, with repeatability standard deviations of 7 and 18% and reproducibility standard deviations of 70 and 90%. Electronic supplementary material The online version of this article (doi:10.1007/s00216-017-0427-2) contains supplementary material, which is available to authorized users.

Background Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system. Results Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material. Conclusions CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications. Electronic supplementary material The online version of this article (10.1186/s12989-019-0309-1) contains supplementary material, which is available to authorized users.

Background Little is known about the exposure levels and adverse health effects of occupational exposure to airplane emissions. Diesel exhaust particles are classified as carcinogenic to humans and jet engines produce potentially similar soot particles. Here, we evaluated the potential occupational exposure risk by analyzing particles from a non-commercial airfield and from the apron of a commercial airport. Toxicity of the collected particles was evaluated alongside NIST standard reference diesel exhaust particles (NIST2975) in terms of acute phase response, pulmonary inflammation, and genotoxicity after single intratracheal instillation in mice. Results Particle exposure levels were up to 1 mg/m3 at the non-commercial airfield. Particulate matter from the non-commercial airfield air consisted of primary and aggregated soot particles, whereas commercial airport sampling resulted in a more heterogeneous mixture of organic compounds including salt, pollen and soot, reflecting the complex occupational exposure at an apron. The particle contents of polycyclic aromatic hydrocarbons and metals were similar to the content in NIST2975. Mice were exposed to doses 6, 18 and 54 μg alongside carbon black (Printex 90) and NIST2975 and euthanized after 1, 28 or 90 days. Dose-dependent increases in total number of cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid were observed on day 1 post-exposure for all particles. Lymphocytes were increased for all four particle types on 28 days post-exposure as well as for neutrophil influx for jet engine particles and carbon black nanoparticles. Increased Saa3 mRNA levels in lung tissue and increased SAA3 protein levels in plasma were observed on day 1 post-exposure. Increased levels of DNA strand breaks in bronchoalveolar lavage cells and liver tissue were observed for both particles, at single dose levels across doses and time points. Conclusions Pulmonary exposure of mice to particles collected at two airports induced acute phase response, inflammation, and genotoxicity similar to standard diesel exhaust particles and carbon black nanoparticles, suggesting similar physicochemical properties and toxicity of jet engine particles and diesel exhaust particles. Given this resemblance as well as the dose-response relationship between diesel exhaust exposure and lung cancer, occupational exposure to jet engine emissions at the two airports should be minimized. Electronic supplementary material The online version of this article (10.1186/s12989-019-0305-5) contains supplementary material, which is available to authorized users.

Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28 d with either: 0.05, 0.5, or 4 mg Se/kg body weight (bw)/day as 20 nm Se nanoparticles or 0.05 or 0.5 mg Se/kg bw/day as sodium selenite. Male rats were dosed 4 mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment. At necropsy, blood samples were taken for hematological and clinical chemistry analyses; organ weights were recorded. At the high-dose of Se nanoparticles, overt toxicity occurred and the female animals had to be euthanized prematurely, whereas the male animals were reduced in dose. At all doses of Se nanoparticles and at 0.5 mg Se/kg bw/day as selenite, a lower body weight gain as compared to vehicle occurred. Relative liver weight was increased for both Se formulations at 0.5 mg Se/kg bw/day. Creatinine clearance and urinary pH were affected in some Se dosed groups. There were no effects among dosed groups on brain neurotransmitters or on hematological parameters compared with controls. There were no histological changes in the livers of animals exposed to Se nanoparticles or to selenite. Based on effects on body weight and liver weight, selenium nanoparticles and ionic Se exerted similar toxicity. This suggests that a nanoparticle-specific toxicity of Se did not occur.

Diesel-powered trains are used worldwide for passenger transport. The present study aimed to assess air pollution concentrations in passenger cars from diesel and electric trains. Personal exposure monitoring (6-7 h per day) was carried out for 49 days on diesel and 22 days on electric trains. Diesel trains had higher concentrations of all the assessed air pollution components. Average increases (and fold differences) in passenger cars of diesel trains compared with electric trains were for ultrafine particles 212 000 particles/cm3 (35-fold), black carbon 8.3 μg/m3 (6-fold), NO x 316 μg/m3 (8-fold), NO2 38 μg/m3 (3-fold), PM2.5 34 μg/m3 (2-fold), and benzo( a)pyrene 0.14 ng/m3 (6-fold). From time-series data, the pull and push movement modes, the engine in use, and the distance to the locomotive influenced the concentrations inside the diesel trains. In conclusion, concentrations of all air pollutants were significantly elevated in passenger cars in diesel trains compared to electric trains.

There is increasing evidence that certain nanoparticles (NPs) can overcome the placental barrier, raising concerns on potential adverse effects on the growing fetus. But even in the absence of placental transfer, NPs may pose a risk to proper fetal development if they interfere with the viability and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D cell cultures, which indicates an enhanced differentiation of trophoblasts grown on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and copper oxide (CuO) NPs but not titanium dioxide (TiO2) NPs decreased MT viability and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs provide a new and promising model for the fast generation of tissue-relevant acute NP toxicity data, which are indispensable for the safe development of NPs for industrial, commercial and medical applications.

Silver is used in a wide range of products, and during their production and use, humans may be exposed through inhalation. Therefore, it is critical to know the concentration levels at which adverse effects may occur. In rodents, inhalation of silver nanoparticles has resulted in increased silver in the lungs, lymph nodes, liver, kidney, spleen, ovaries, and testes. Reported excretion pathways of pulmonary silver are urinary and faecal excretion. Acute effects in humans of the inhalation of silver include lung failure that involved increased heart rate and decreased arterial blood oxygen pressure. Argyria—a blue-grey discoloration of skin due to deposited silver—was observed after pulmonary exposure in 3 individuals; however, the presence of silver in the discolorations was not tested. Argyria after inhalation seems to be less likely than after oral or dermal exposure. Repeated inhalation findings in rodents have shown effects on lung function, pulmonary inflammation, bile duct hyperplasia, and genotoxicity. In our evaluation, the range of NOAEC values was 0.11–0.75 mg/m3. Silver in the ionic form is likely more toxic than in the nanoparticle form but that difference could reflect their different biokinetics. However, silver nanoparticles and ions have a similar pattern of toxicity, probably reflecting that the effect of silver nanoparticles is primarily mediated by released ions. Concerning genotoxicity studies, we evaluated silver to be positive based on studies in mammalian cells in vitro and in vivo when considering various exposure routes. Carcinogenicity data are absent; therefore, no conclusion can be provided on this endpoint.

Background Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO2), cerium oxide (CeO2) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control. Results Liver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO2 or CeO2. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO2 and CeO2 NPs, CB NPs generated ROS in an acellular assay. Conclusions Our results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response. Electronic supplementary material The online version of this article (10.1186/s12989-017-0238-9) contains supplementary material, which is available to authorized users.

Silver is used in different applications that result in contact with skin and mucosal surfaces (e.g., jewelry, wound dressings, or eye drops). Intact skin poses an effective barrier against the absorption of silver. Mucosal surfaces are observed to be less effective barriers and compromised skin is often a poor barrier. Silver can deposit as particles in the human body causing a blue-gray discoloration known as argyria. Urine and feces are reported pathways of excretion. Acute human mortality has been observed following an abortion procedure involving the intrauterine administration of 7 g silver nitrate (64 mg silver/kg body weight). Localized argyria has been reported with exposure to silver ions, metallic surfaces, and nanocrystalline silver. Generalized argyria was observed with ionic and nanocrystalline silver in humans at cumulative doses in the range of 70–1500 mg silver/kg body weight. Silver is observed to have a low potential for skin irritation. Eye irritation and some cases of allergic contact dermatitis have been reported. Silver may cause genotoxicity, but additional data are required to assess its carcinogenic potential. Other reported toxicities include hepatic, renal, neurological, and hematological effects.

We tested the suitability of asymmetric flow field-flow fractionation (AF4) coupled to multi-angle light scattering (MALS) for detection of nanoplastics in fish. A homogenized fish sample was spiked with 100 nm polystyrene nanoparticles (PSNPs) (1.3 mg/g fish). Two sample preparation strategies were tested: acid digestion and enzymatic digestion with proteinase K. Both procedures were found suitable for degradation of the organic matrix. However, acid digestion resulted in large PSNPs aggregates/agglomerates (> 1 μm). The presence of large particulates was not observed after enzymatic digestion, and consequently it was chosen as a sample preparation method. The results demonstrated that it was possible to use AF4 for separating the PSNPs from the digested fish and to determine their size by MALS. The PSNPs could be easily detected by following their light scattering (LS) signal with a limit of detection of 52 μg/g fish. The AF4-MALS method could also be exploited for another type of nanoplastics in solution, namely polyethylene (PE). However, it was not possible to detect the PE particles in fish, due to the presence of an elevated LS background. Our results demonstrate that an analytical method developed for a certain type of nanoplastics may not be directly applicable to other types of nanoplastics and may require further adjustment. This work describes for the first time the detection of nanoplastics in a food matrix by AF4-MALS. Despite the current limitations, this is a promising methodology for detecting nanoplastics in food and in experimental studies (e.g., toxicity tests, uptake studies). Graphical abstract Basic concept for the detection of nanoplastics in fish by asymmetric flow field-flow fractionation coupled to multi-angle light scattering.

Research on the potential migration of nanoparticles (NPs) from nano-based food contact materials (FCMs) has often reached inconsistency in previous studies. Conventional food simulants and traditional migration tests, which are established for small molecules, have been used for studying the potential migration of NPs from nano-based FCMs. The suitability of conventional food simulants and migration tests was investigated by studying the behavior of 40 nm polyethylene glycol (PEG) coated AgNPs and silver ions in food simulants (10% ethanol, 20% ethanol, 50% ethanol, 3% acetic acid, olive oil) under migration conditions. Particle mass and number concentrations, ionic concentration and particle size distributions were determined by single particle inductively coupled plasma-mass spectrometry (spICP-MS) before and after incubation for 4 h or 10 days at 40 °C. In agreement with similar studies, 50% ethanol preserved the AgNPs, while acetic acid induced dissolution of AgNPs. Dissolution of the PEG-AgNPs obeyed pseudo-first-order reaction kinetics. PEG-AgNPs showed similar behavior in low fat cow milk during storage at 4 °C for 5 days as in the corresponding food simulant, 50% ethanol. Addition of sodium chloride to ultrapure water led to enhanced dissolution. The potential reduction of silver ions to NPs in food simulants, low fat milk and in alkaline conditions in the presence of reducing agents was studied. Based on the obtained results, it is unlikely that AgNPs are formed from Ag ions at the low concentration which are typically observed for the migration of Ag from polymeric FCMs.

Nanomaterials are increasingly used in food production and packaging, and validated methods for detection of nanoparticles (NPs) in foodstuffs need to be developed both for regulatory purposes and product development. Asymmetric flow field-flow fractionation with inductively coupled plasma mass spectrometric detection (AF(4)-ICP-MS) was applied for quantitative analysis of silver nanoparticles (AgNPs) in a chicken meat matrix following enzymatic sample preparation. For the first time an analytical validation of nanoparticle detection in a food matrix by AF(4)-ICP-MS has been carried out and the results showed repeatable and intermediately reproducible determination of AgNP mass fraction and size. The findings demonstrated the potential of AF(4)-ICP-MS for quantitative analysis of NPs in complex food matrices for use in food monitoring and control. The accurate determination of AgNP size distribution remained challenging due to the lack of certified size standards.