Filling the knowledge gap: A suspect screening study for 1310 potentially persistent and mobile chemicals with SFC- and HILIC-HRMS in two German river systems.

Persistent and mobile chemicals (PM chemicals) were searched for in surface waters by hydrophilic interaction liquid chromatography (HILIC) and supercritical fluid chromatography (SFC), both coupled to high resolution mass spectrometry (HRMS). A suspect screening was performed using a newly compiled list of 1310 potential PM chemicals to the data of 11 surface water samples from two river systems. In total, 64 compounds were identified by this approach. The overlap between HILIC- and SFC-HRMS was limited (31 compounds), confirming the complementarity of the two methods used. The identified PM candidates are characterized by a high polarity (median logD -0.4 at pH 7.5), a low molecular weight (median 187 g/mol), are mostly ionic (54 compounds) and contain a large number of heteroatoms (one per four carbons on average). Among the most frequently detected novel or yet scarcely investigated water contaminants were cyanoguanidine (11/11 samples), adamantan-1-amine (10/11), trifluoromethanesulfonate (9/11), 2-acrylamido-2-methylpropanesulfonate (10/11), and the inorganic anions hexafluorophosphate (11/11) and tetrafluoroborate (10/11). 31% of the identified suspects are mainly used in ionic liquids, a chemically diverse group of industrial chemicals with numerous applications that is so far rarely studied for their occurrence in the environment. Prioritization of the findings of PM candidates is hampered by the apparent lack of toxicity data. Hence, precautionary principles and minimization approaches should be applied for the risk assessment and risk management of these substances. The large share of novel water contaminants among these findings of the suspect screening indicates that the universe of PM chemicals present in the environment has so far only scarcely been explored. Dedicated analytical methods and screening lists appear essential to close the analytical gap for PM compounds.

Quaternary (triphenyl-) phosphonium compounds: Environmental behavior and toxicity.

An analytical method based on high resolution mass spectrometry coupled with liquid chromatography (LC-HRMS) for 25 quaternary phosphonium compounds (QPCs) and derived phosphine oxides (POs) was developed and validated. To investigate the occurrence and fate of QPCs in the aquatic environment, water, suspended solids and sediments from the rivers Rhine and Elbe (upper and middle Elbe as well as tidal Elbe) were analyzed, as well as samples from tributaries bearing significant loads of QPCs. For the first time, the quaternary phosphonium compound tetrabutylphosphonium (Bu4P+) was detected. In the river Elbe concentrations were determined of up to 4700 ng/L (surface water) and 1000 µg/kg (sediment), respectively. Analysis of a time series of suspended solids (2005-2015) showed that QPCs have been present in the Elbe and Rhine catchment for at least one decade, with partly rising tendency. A degradation experiment with Rhine sediment revealed that triphenylphosphonium compounds (R-Ph3P+) and Bu4P+ are persistent in contact with sediment and suspended solids and tend to sorb onto sediment particles. Toxicological studies (reactive oxygen species (ROS) after substance exposure, Ames test, Micronucleus test, determination of cytotoxicity) with selected QPCs confirmed that all of them exhibit cytotoxicity and some even genotoxic potential at elevated concentrations, which emphasizes the need for an emission regulation of these compounds.

Cell membrane penetration and mitochondrial targeting by platinum-decorated ceria nanoparticles.

In this work we investigate the interaction between endothelial cells and nanoparticles emitted by catalytic converters. Although catalyst-derived particles are recognized as growing burden added to environmental pollution, very little is known about their health impact. We use platinum-decorated ceria nanoparticles as model compounds for the actual emitted particles and focus on their fast uptake and association with mitochondria, the cell's powerhouse. Using live-cell imaging and electron microscopy we clearly show that 46 nm platinum-decorated ceria nanoparticles can rapidly penetrate cell membranes and reach the cytosol. Moreover, if suitably targeted, these particles are able to selectively attach to mitochondria. These results are complemented by cytotoxicity assays, thus providing insights into the biological effects of these particles on cells. Interestingly, no permanent membrane disruption or any other significant adverse effects on cells were observed. The unusual uptake behavior observed for 46 nm nanoparticles was not observed for equivalent but larger 143 nm and 285 nm platinum-decorated particles. Our results demonstrate a remarkable particle size effect in which particles smaller than ∼50-100 nm escape the usual endocytic pathway and translocate directly into the cytosol, while particles larger than ∼150 nm are internalized by conventional endocytosis. Since the small particles are able to bypass endocytosis they could be explored as drug and gene delivery vehicles. Platinum-decorated nanoparticles are therefore highly interesting in the fields of nanotoxicology and nanomedicine.

Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis.

Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-ß-cyclodextrin (MßcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO2 nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MßcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO2 nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells.

Biocompatibility of cerium dioxide and silicon dioxide nanoparticles with endothelial cells.

Cerium dioxide (CeO2) and silicon dioxide (SiO2) nanoparticles are of widespread use in modern life. This means that human beings are markedly exposed to them in their everyday life. Once passing biological barriers, these nanoparticles are expected to interact with endothelial cells, leading to systemic alterations with distinct influences on human health. In the present study we observed the metabolic impact of differently sized CeO2 (8 nm; 35 nm) and SiO2 nanoparticles (117 nm; 315 nm) on immortalized human microvascular (HMEC-1) and primary macrovascular endothelial cells (HUVEC), with particular focus on the CeO2 nanoparticles. The characterization of the CeO2 nanoparticles in cell culture media with varying serum content indicated a steric stabilization of nanoparticles due to interaction with proteins. After cellular uptake, the CeO2 nanoparticles were localized around the nucleus in a ring-shaped manner. The nanoparticles revealed concentration and time, but no size-dependent effects on the cellular adenosine triphosphate levels. HUVEC reacted more sensitively to CeO2 nanoparticle exposure than HMEC-1. This effect was also observed in relation to cytokine release after nanoparticle treatment. The CeO2 nanoparticles exhibited a specific impact on the release of diverse proteins. Namely, a slight trend towards pro-inflammatory effects, a slight pro-thrombotic impact, and an increase of reactive oxygen species after nanoparticle exposure were observed with increasing incubation time. For SiO2 nanoparticles, concentration- and time-dependent effects on the metabolic activity as well as pro-inflammatory reactions were detectable. In general, the effects of the investigated nanoparticles on endothelial cells were rather insignificant, since the alterations on the metabolic cell activity became visible at a nanoparticle concentration that is by far higher than those expected to occur in the in vivo situation (CeO2 nanoparticles: 100 µg/mL; SiO2 nanoparticles: 10 µg/mL).

Effects of the physicochemical properties of titanium dioxide nanoparticles, commonly used as sun protection agents, on microvascular endothelial cells.

Until now, the potential effects of titanium dioxide (TiO2) nanoparticles on endothelial cells are not well understood, despite their already wide usage. Therefore, the present work characterizes six TiO2 nanoparticle samples in the size range of 19 × 17 to 87 × 13 nm, which are commonly present in sun protection agents with respect to their physicochemical properties (size, shape, ζ-potential, agglomeration, sedimentation, surface coating, and surface area), their interactions with serum proteins and biological impact on human microvascular endothelial cells (relative cellular dehydrogenase activity, adenosine triphosphate content, and monocyte chemoattractant protein-1 release). We observed no association of nanoparticle morphology with the agglomeration and sedimentation behavior and no variations of the ζ-potential (-14 to -19 mV) in dependence on the surface coating. In general, the impact on endothelial cells was low and only detectable at concentrations of 100 µg/ml. Particles containing a rutile core and having rod-like shape had a stronger effect on cell metabolism than those with anatase core and elliptical shape (relative cellular dehydrogenase activity after 72 h: 60 vs. 90 %). Besides the morphology, the nanoparticle shell constitution was found to influence the metabolic activity of the cells. Upon cellular uptake, the nanoparticles were localized perinuclearly. Considering that in the in vivo situation endothelial cells would come in contact with considerably lower nanoparticle amounts than the lowest-observable adverse effects level (100 µg/ml), TiO2 nanoparticles can be considered as rather harmless to humans under the investigated conditions.

Survey of n-3 and n-6 polyunsaturated fatty acids in fish and fish products.

BACKGROUND: The imbalance of the n-3/n-6 ratio in the Western diet is characterised by a low intake of n-3 long-chain (LC) PUFA and a concurrent high intake of n-6 PUFA. Fish, in particular marine fish, is a unique source of n-3 LC PUFA. However, FA composition of consumed fish changed, due to the increasing usage of n-6 PUFA-rich vegetable oils in aquaculture feed and in fish processing (frying) which both lead to a further shift in n-6 PUFA to the detriment of n-3 LC PUFA.The aim of this study was to determine the ratio of n-3/n-6 including the contents of EPA and DHA in fish fillets and fish products from the German market (n=123). Furthermore, the study focussed on the FA content in farmed salmon compared to wild salmon as well as in processed Alaska pollock fillet, e.g., fish fingers. RESULTS: Total fat and FA content in fish products varied considerably depending on fish species, feed management, and food processing. Mackerel, herring and trout fillets characteristically contained adequate dietary amounts of absolute EPA and DHA, due to their high fat contents. However, despite a lower fat content, tuna, pollock, and Alaska pollock can contribute considerable amounts of EPA and DHA to the human supply.Farmed salmon are an appropriate source of EPA and DHA owing to their higher fat content compared to wild salmon (12.3 vs. 2.1 wt %), however with elevated SFA, n-9 and n-6 FA contents representing the use of vegetable oils and oilseeds in aquaculture feed. The n-3/n-6 ratio was deteriorated (2.9 vs. 12.4) but still acceptable. Compared to pure fish fillets, breaded and pre-fried Alaska pollock fillet contained extraordinarily high fat and n-6 PUFA levels. CONCLUSIONS: Since fish species vary with respect to their n-3 LC PUFA contents, eating a variety of fish is advisable. High n-6 PUFA containing pre-fried fish support the imbalance of n-3/n-6 ratio in the Western diet. Thus, consumption of pure fish fillets is to be favoured. The lower n-3 PUFA portion in farmed fish can be offset by the higher fat content, however, with an unfavourable FA distribution compared to wild fellows.