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The neurotoxicity of hard metal‐based nanoparticles (NPs) remains poorly understood. Here, we deployed the human neuroblastoma cell line SH‐SY5Y differentiated or not into dopaminergic‐ and cholinergic‐like neurons to study the impact of tungsten carbide (WC) NPs, WC NPs sintered with cobalt (Co), or Co NPs versus soluble CoCl2. Co NPs and Co salt triggered a dose‐dependent cytotoxicity with an increase in cytosolic calcium, lipid peroxidation, and depletion of glutathione (GSH). Co NPs and Co salt also suppressed glutathione peroxidase 4 (GPX4) mRNA and protein expression. Co‐exposed cells were rescued by N‐acetylcysteine (NAC), a precursor of GSH, and partially by liproxstatin‐1, an inhibitor of lipid peroxidation. Furthermore, in silico analyses predicted a significant correlation, based on similarities in gene expression profiles, between Co‐containing NPs and Parkinson's disease, and changes in the expression of selected genes were validated by RT‐PCR. Finally, experiments using primary human dopaminergic neurons demonstrated cytotoxicity and GSH depletion in response to Co NPs and CoCl2 with loss of axonal integrity. Overall, these data point to a marked neurotoxic potential of Co‐based but not WC NPs and show that neuronal cell death may occur through a ferroptosis‐like mechanism. [ABSTRACT FROM AUTHOR]

• Effect of surface finish on corrosion and metal release from Ti6Al4V studied. • Ti6Al4V was produced by laser powder bed fusion using biomedical protocols. • Nitric acid passivation had a negligible effect on metal release and corrosion. • Effect of surface finish (sandblasted, polished) explained by true surface area. • More proteins were adsorbed on rough (sandblasted) surfaces. The biomedical titanium alloy Ti6Al4V has excellent corrosion resistance and biocompatibility and is, therefore, widely used in orthopedic and orthodontic implants. Biomedical implants are increasingly fabricated by additive manufacturing, such as laser powder bed fusion (LPBF). These manufacturing protocols often include sandblasting, surface finish, and passivation. This study aims to investigate the effect of different surface finishes and the commonly used ASTM F86–13 nitric acid passivation for LPBF Ti6Al4V on its corrosion resistance, metal release, and surface changes in benign (bovine serum albumin in a pH 7.4 buffer) and harsh (hydrochloric acid at pH 1.5) solutions using various electrochemical and spectroscopic techniques. Electrochemical, solution and surface analysis showed an insignificant effect of passivation. Smooth surfaces exhibited a slightly better corrosion resistance than rough surfaces due to a 10–20 % smaller true surface area and lower protein adsorption. Implanted ceramic beads from the sandblasting procedure remained on the surface even after the mirror-polishing and passivation procedures. [Display omitted] [ABSTRACT FROM AUTHOR]

Stainless steel is widely used in biological environments, for example as implant material or in food applications, where adsorption-controlled ligand-induced metal release is of importance from a corrosion, health, and food safety perspective. The objective of this study was to elucidate potential correlations between surface energy and wettability of stainless steel surfaces and the release of iron in complexing biological media. This was accomplished by studying changes in surface energies calculated from contact angle measurements, surface oxide composition (X-ray photoelectron spectroscopy), and released iron (graphite furnace atomic absorption spectroscopy) for stainless steel grade AISI 304 immersed in fluids containing bovine serum albumin or citric acid, and non-complexing fluids such as NaCl, NaOH, and HNO 3 . It was shown that the surface wettability and polar surface energy components were all influenced by adventitious atmospheric carbon (surface contamination of low molecular weight), rather than differences in surface oxide composition in non-complexing solutions. Adsorption of both BSA and citrate, which resulted in ligand-induced metal release, strongly influenced the wettability and the surface energy, and correlated well with the measured released amount of iron. [ABSTRACT FROM AUTHOR]

Introduction: Traces of hexavalent chromium, Cr(VI), are a major concern for skin contact with Cr-tanned leather. Current extraction methods (ISO 17075-1:2017) for Cr(VI) testing do not necessarily reflect the true potential of surface-formed Cr(VI), as extracted concentrations are dependent on previous storage and atmospheric conditions., Objectives: To test whether a spiking method protocol can distinguish leathers with high and low risks of releasing Cr(VI)., Methods: Two groups of leather types were selected based on previously detected Cr(VI) (group A) and optimal tanning practices with high antioxidants (group B), corresponding to a high and low risk of forming and keeping Cr(VI). Leathers were spiked with different concentrations up to 10 mg/kg of Cr(VI) and incubated at 80°C for 24 h prior to the ISO 17075-1:2017 extraction protocol., Results: All Cr(VI) was reduced by group B leathers, whereas all group A leather extracts contained detectable Cr(VI) that was dependent on the exact leather type and the amount initially spiked., Conclusion: Pre-treatment of samples with supplemental Cr(VI) is a potential method for determining the reduction capabilities of leather, which are closely related to the risk of Cr(VI) formation. 10 mg/kg spiking unambiguously distinguished leathers with high and low risks of forming Cr(VI)., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Introduction: Leather has been a significant source of chromium (Cr) allergy in Denmark since the 1990s. More recently, cobalt (Co) allergy has been identified in leather as a source of allergic contact dermatitis., Objectives: To measure Cr and Co levels in Danish leather goods., Methods: A total of 87 leather samples were collected, all tanned in Europe. Handheld X-ray fluorescence (XRF) device was used to screen for the presence of Cr and Co. The 20 leather samples with the highest concentrations of Co and Co were tested using International Organization for Standardization (ISO)-standards., Results: XRF analysis showed Cr in 78/87 (83.9%) samples and Co in 52/87 (59.7%), with average concentrations of 41 mg/kg (range: 0.0-77 mg/kg) and 0.22 mg/kg (range: 0.0-2.9 mg/kg), respectively. ISO 10195 and 17 075-1 testing identified Cr (VI) in 7 out of 20 samples (1.4; 0.3-4.2 mg/kg), while ISO 17072-1 detected Co in 6 of 20 samples, averaging 3.95 mg/kg (range: 0.22-7.9 mg/kg)., Conclusion: Most leather samples contained Cr, which was expected, while Cr (VI) was detectable in seven out of twenty tested samples but only detected in one product above the regulatory limit of 3 mg/kg. A potentially significant concentration was found for Co., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Diffusely dispersed metal and metal oxide nanoparticles (NPs) can adversely affect living organisms through various mechanisms and exposure routes. One mechanism behind their toxic potency is their ability to generate reactive oxygen species (ROS) directly or indirectly to an extent that depends on the dose, metal speciation, and exposure route. This review provides an overview of the mechanisms of ROS formation associated with metal and metal oxide NPs and proposes a possible way forward for their future categorization. Metal and metal oxide NPs can form ROS via processes related to corrosion, photochemistry, and surface defects, as well as via Fenton, Fenton-like, and Haber-Weiss reactions. Regular ligands such as biomolecules can interact with metallic NP surfaces and influence their properties and thus their capabilities of generating ROS by changing characteristics such as surface charge, surface composition, dissolution behavior, and colloidal stability. Interactions between metallic NPs and cells and their organelles can indirectly induce ROS formation via different biological responses. H 2 O 2 can also be generated by a cell due to inflammation, induced by interactions with metallic NPs or released metal species that can initiate Fenton(-like) and Haber-Weiss reactions forming various radicals. This review discusses these different pathways and, in addition, nano-specific aspects such as shifts in the band gaps of metal oxides and how these shifts at biologically relevant energies (similar to activation energies of biological reactions) can be linked to ROS production and indicate which radical species forms. The influences of kinetic aspects, interactions with biomolecules, solution chemistry (e.g., Cl - and pH), and NP characteristics (e.g., size and surface defects) on ROS mechanisms and formation are discussed. Categorization via four tiers is suggested as a way forward to group metal and metal oxide NPs based on the ROS reaction pathways that they may undergo, an approach that does not include kinetics or environmental variations. The criteria for the four tiers are based on the ability of the metallic NPs to induce Fenton(-like) and Haber-Weiss reactions, corrode, and interact with biomolecules and their surface catalytic properties. The importance of considering kinetic data to improve the proposed categorization is highlighted.

Increased use and production of engineered nanoparticles (NPs) lead to an elevated risk of their diffuse dispersion into the aquatic environment and increased concern on unknown effects induced by their release into the aquatic ecosystem. An improved understanding of the environmental transformation processes of NPs of various surface characteristics is hence imperative for risk assessment and management. This study presents results on effects of natural organic matter (NOM) on the environmental transformation and dissolution of metal and metal oxide NPs of different surface and solubility properties in synthetic freshwater (FW) with and without NOM. Adsorption of NOM was evident on most of the studied NPs, except Sb and Sb 2 O 3 , which resulted in the formation of negatively charged colloids of higher stability and smaller size distribution compared with the same NPs in FW only. The dissolution rate of the NPs in the presence of NOM correlated with the strength of interactions between the carboxylate group of NOM and the particle surface, and resulted in either no (Mn, Sb, ZnO NPs), increased (Co, Sn NPs) and decreased (Ni, NiO, Sb 2 O 3 , Y 2 O 3 NPs) levels of dissolution. One type of metal NP from each group (Mn, Ni, Sn) were investigated to assess whether observed differences in adsorption of NOM and dissolution would influence their ecotoxic potency. The results showed Mn, Ni, and Sn NPs to generate intracellular reactive oxygen species (ROS) in a time and dose-dependent manner. The extent of ROS generation in FW was similar for both Mn and Ni NPs but higher for Sn NPs. These findings are possibly related to interactions and infiltration of the NPs with the cells, which lead to redox imbalances which could induce oxidative stress and cell damage. At the same time, the presence of NOM generally reduced the intracellular ROS generation by 20-40% for the investigated NPs and also reduced cytotoxicity of Sn NPs, which can be attributed to the stronger interaction of carboxylate groups of NOM with the surface of the NPs., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) together with the enzyme horseradish peroxidase (HRP) is widely used in nanotoxicology to study acellular reactive oxygen species (ROS) production from nanoparticles (NPs). This study examined whether HRP adsorbs onto NPs of Mn, Ni, and Cu and if this surface process influences the extent of metal release and hence the ROS production measurements using the DCFH assay in phosphate buffered saline (PBS), saline, or Dulbecco's modified Eagle's medium (DMEM). Adsorption of HRP was evident onto all NPs and conditions, except for Mn NPs in PBS. The presence of HRP resulted in an increased release of copper from the Cu NPs in PBS and reduced levels of nickel from the Ni NPs in saline. Both metal ions in solution and the adsorption of HRP onto the NPs can change the activity of HRP and thus influence the ROS results. The effect of HRP on the NP reactivity was shown to be solution chemistry dependent. Most notable was the evident affinity/adsorption of phosphate toward the metal NPs, followed by a reduced adsorption of HRP, the concomitant reduction in released manganese from the Mn NPs, and increased levels of released metals from the Cu NPs in PBS. Minor effects were observed for the Ni NPs. The solution pH should be monitored since the release of metals can change the solution pH and the activity of HRP is known to be pH-dependent. It is furthermore essential that solution pH adjustments are made following the addition of NaOH during diacetyl removal of DCFH-DA. Even though not observed for the given exposure conditions of this study, released metal ions could possibly induce agglomeration or partial denaturation of HRP, which in turn could result in steric hindrance for H 2 O 2 to reach the active site of HRP. This study further emphasizes the influence of HRP on the background kinetics, its solution dependence, and effects on measured ROS signals. Different ways of correcting for the background are highlighted, as this can result in different interpretations of generated results. The results show that adsorption of HRP onto the metal NPs influenced the extent of metal release and may, depending on the investigated system, result in either under- or overestimated ROS signals if used together with the DCFH assay. HRP should hence be used with caution when measuring ROS in the presence of reactive metallic NPs.

As the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP's) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC-Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC-Co NPs the survival time increased with 20-25% and for Co NPs with 30-47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems.

Pure metallic Co, Ni, and their bimetallic compositions of Co 3 Ni, CoNi, and CoNi 3 nanomaterials were prepared by solution combustion synthesis. Microstructure, phase composition, and crystalline structure of these nanoparticles (NPs) were characterized along with studies of their corrosion and dissolution properties in synthetic freshwater with and without natural organic matter (NOM). The nanomaterials consisted of aggregates of fine NPs (3-30 nm) of almost pure metallic and bimetallic crystal phases with a thin surface oxide covered by a thin carbon shell. The nanomaterials were characterized by BET surface areas ranging from ~ 1 to 8 m 2 /g for the Ni and Co NPs, to 22.93 m 2 /g, 14.86 m 2 /g, and 10.53 m 2 /g for the Co 3 Ni, CoNi, CoNi 3 NPs, respectively. More Co and Ni were released from the bimetallic NPs compared with the pure metals although their corrosion current densities were lower. In contrast to findings for the pure metal NPs, the presence of NOM increased the release of Co and Ni from the bimetallic NPs in freshwater compared to freshwater only even though its presence reduced the corrosion rate (current density). It was shown that the properties of the bimetallic nanomaterials were influenced by multiple factors such as their composition, including carbon shell, type of surface oxides, and the entropy of mixing.

Gold (Au) nanoparticles (NPs) are widely used in nanomedical applications as a carrier for molecules designed for different functionalities. Previous findings suggested that biological molecules, including amino acids, could contribute to the dissolution of Au NPs in physiological environments and that this phenomenon was size-dependent. We, therefore, investigated the interactions of L-cysteine with 5-nm Au NPs by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS). This was achieved by loading Au NPs on a clean aluminum (Al) foil and immersing it in an aqueous solution containing L-cysteine. Upon rinsing off the excessive cysteine molecules, ToF-SIMS confirmed the formation of gold cysteine thiolate via the detection of not only the Au-S bond but also the hydrogenated gold cysteine thiolate molecular ion. The presence of NaCl or a 2-(N-morpholino)ethanesulfonic acid buffer disabled the detection of Au NPs on the Al foil. The detection of larger (50-nm) Au NPs was possible but resulted in weaker cysteine and gold signals, and no detected gold cysteine thiolate signals. Nano-gold specific adsorption of L-cysteine was also demonstrated by cyclic voltammetry using paraffine-impregnated graphite electrodes with deposited Au NPs. We demonstrate that the superior chemical selectivity and surface sensitivity of ToF-SIMS, via detection of elemental and molecular species, provide a unique ability to identify the adsorption of cysteine and formation of gold-cysteine bonds on Au NPs.

The use of silver nanoparticles (Ag NPs) in consumer products can result in diffuse environmental dispersion of both NPs and ionic silver. This study investigated the transformation of Ag NPs present in two consumer products (skin cream, mouth spray) in terms of release of Ag NPs and ionic silver and changes in particle size in artificial sweat and saliva solutions. Large differences in silver release were observed with the smaller sized Ag NPs in mouth spray releasing more silver compared with the Ag NPs of the skin cream. Substantial particle agglomeration took place in both artificial sweat and saliva, forming large-sized agglomerates (> 100 nm). The amount of dissolved silver in solution after 24 h was less than 10% of the total amount of Ag NPs for both products. The results show that the Ag NPs of these consumer products will largely remain as NPs even after 24 h of skin or saliva contact. The use of normalization by geometric surface area of the particles was tested as a way to compare dissolution for Ag NPs of different characteristics, including pristine, bare, as well as PVP-capped Ag NPs. Normalization of silver dissolution with the geometric surface area was shown promising, but more extensive studies are required to unambiguously conclude whether it is a way forward to enable grouping of the dissolution behavior of Ag NPs released from consumer products.

Studded tyres made of tungsten carbide cobalt (WC-Co) are in the Northern countries commonly used during the winter time. Tungsten (W)-containing nano- and micron-sized particles have been detected close to busy roads in several European countries. Other typical traffic wear particles consist of copper (Cu). The aims of this study were to investigate particle stability and transformation/dissolution properties of nanoparticles (NPs) of WC-Co compared with NPs of tungsten carbide (WC), cobalt (Co), and Cu. Their physicochemical characteristics (primarily surface oxide and charge) are compared with their extent of sedimentation and metal release in synthetic surface water (SW) with and without two different model organic molecules, 2,3- and 3,4-dihydroxybenzoic acid (DHBA) mimicking certain sorption sites of humic substances, for time periods up to 22 days. The WC-Co NPs possessed a higher electrochemical and chemical reactivity in SW with and without DHBA molecules as compared with NPs of WC, Co, and Cu. Co was completely released from the WC-Co NPs within a few hours of exposure, although it remained adsorbed/bonded to the particle surface and enabled the adsorption of negatively charged DHBA molecules, in contrast with the WC NPs (no adsorption of DHBA). The DHBA molecules were found to rapidly adsorb on the Co and Cu NPs. The sedimentation of the WC and WC-Co NPs was not influenced by the presence of the 2,3- or 3,4-DHBA molecules. A slight influence (slower sedimentation) was observed for the Co NPs, and a strong influence (slower sedimentation) was observed for the Cu NPs in SW with 2,3-DHBA compared with SW alone. The extent of metal release increased in the order: WC < Cu < Co < WC-Co NPs. All NPs released more than 1 wt-% of their metal total mass. The release from the Cu NPs was most influenced by the presence of DHBA molecules., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Copper nanoparticles (Cu NPs) are increasingly used in various biologically relevant applications and products, e.g., due to their antimicrobial and catalytic properties. This inevitably demands for an improved understanding on their interactions and potential toxic effects on humans. The aim of this study was to investigate the corrosion of copper nanoparticles in various biological media and to elucidate the speciation of released copper in solution. Furthermore, reactive oxygen species (ROS) generation and lung cell (A549 type II) membrane damage induced by Cu NPs in the various media were studied. The used biological media of different complexity are of relevance for nanotoxicological studies: Dulbecco's modified eagle medium (DMEM), DMEM(+) (includes fetal bovine serum), phosphate buffered saline (PBS), and PBS+histidine. The results show that both copper release and corrosion are enhanced in DMEM(+), DMEM, and PBS+histidine compared with PBS alone. Speciation results show that essentially no free copper ions are present in the released fraction of Cu NPs in neither DMEM(+), DMEM nor histidine, while labile Cu complexes form in PBS. The Cu NPs were substantially more membrane reactive in PBS compared to the other media and the NPs caused larger effects compared to the same mass of Cu ions. Similarly, the Cu NPs caused much more ROS generation compared to the released fraction only. Taken together, the results suggest that membrane damage and ROS formation are stronger induced by Cu NPs and by free or labile Cu ions/complexes compared with Cu bound to biomolecules., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: In this study, we elucidate the effect of different sonication techniques to efficiently prepare particle dispersions from selected non-functionalized NPs (Cu, Al, Mn, ZnO), and corresponding consequences on the particle dose, surface charge and release of metals. Probe sonication was shown to be the preferred method for dispersing non-inert, non-functionalized metal NPs (Cu, Mn, Al). However, rapid sedimentation during sonication resulted in differences between the real and the administered doses in the order of 30-80 % when sonicating in 1 and 2.56 g/L NP stock solutions. After sonication, extensive agglomeration of the metal NPs resulted in rapid sedimentation of all particles. DLVO calculations supported these findings, showing the strong van der Waals forces of the metal NPs to result in significant NP agglomeration. Metal release from the metal NPs was slightly increased by increased sonication. The addition of a stabilizing agent (bovine serum albumin) had an accelerating effect on the release of metals in sonicated solutions. For Cu and Mn NPs, the extent of particle dissolution increased from <1.6 to ~5 % after sonication for 15 min. A prolonged sonication time (3-15 min) had negligible effects on the zeta potential of the studied NPs. In all, it is shown that it is of utmost importance to carefully investigate how sonication influences the physico-chemical properties of dispersed metal NPs. This should be considered in nanotoxicology investigations of metal NPs.

The increasing use of silver nanoparticles (AgNPs) in consumer products triggers the need for investigations that improve the understanding of their chemical transformations upon environmental entry. Such knowledge provides crucial information for toxicological studies and risk assessments. Interactions with the soil compartment need to be explored as there are evident risks of the dispersion of both AgNPs and of released Ag ions/complexes present in wastewater-treated sludge that is distributed onto agricultural land. The dissolution and fractionation in solution of bare (AgNP-bare, noncoated) and coated AgNPs (AgNP-coat, stabilized with two nonionic surfactants, polyoxyethylene glycerol trioleate and Tween 20) were investigated after 4 and 48 h in suspensions of one sandy and one clayey soil of different pHs (3.3, 5.2). Parallel experiments were performed with soil suspensions spiked with easily soluble AgNO3. Silver in the water phase was separated in a dissolved fraction (mainly Ag ions/complexes) and a particle fraction (mainly AgNP/agglomerates/Ag adsorbed on organic matter) by means of ultracentrifugation. Bare AgNPs were nonstable and dissolved to a significantly larger extent in the sandy soil mixture compared to coated AgNPs. The concentration of dissolved Ag (ions/complexes) in the water phase was similar in the case of bare AgNPs and AgNO3 (at pH 3 and 5.2) after 24 h in sandy soil, which implies a high degree of dissolution of bare AgNPs (50-100%). In contrast, approximately 50% of the coated AgNPs remained in the water phase after 48 h of equilibration in the sandy soil at pH 5.2. The clayey soil had a significantly higher sorption capacity of Ag compared with the sandy soil, as Ag in the case of coated AgNPs was only detected in the water phase of pH 5.2 (<1% of added Ag). Ultracentrifugation was proven more efficient compared with microfiltration to separate the dissolved Ag fraction (ions/complexes) and the particle fraction (AgNPs/agglomerates) of the water phase. This fractionation is not a measure of any potential toxicity.

Iron, chromium, nickel, and manganese released from gas-atomized AISI 316L stainless steel powders (sized <45 and <4 μm) were investigated in artificial lysosomal fluid (ALF, pH 4.5) and in solutions of its individual inorganic and organic components to determine its most aggressive component, elucidate synergistic effects, and assess release mechanisms, in dependence of surface changes using atomic absorption spectroscopy, Raman, XPS, and voltammetry. Complexation is the main reason for metal release from 316L particles immersed in ALF. Iron was mainly released, while manganese was preferentially released as a consequence of the reduction of manganese oxide on the surface. These processes resulted in highly complexing media in a partial oxidation of trivalent chromium to hexavalent chromium on the surface. The extent of metal release was partially controlled by surface properties (e.g., availability of elements on the surface and structure of the outermost surface) and partially by the complexation capacity of the different metals with the complexing agents of the different media. In general, compared to the coarse powder (<45 μm), the fine (<4 μm) powder displayed significantly higher released amounts of metals per surface area, increased with increased solution complexation capacity, while less amounts of metals were released into non-complexing solutions. Due to the ferritic structure of lower solubility for nickel of the fine powder, more nickel was released into all solutions compared with the coarser powder.