Synthetic Amorphous Silica Research Articles

PROSPECTS FOR USING A COBALT CATALYST FOR FISHER-TROPSCH SYNTHESIS BASED ON SYNTHETIC SILICA ALUMINA

The possibility of the use of commercially available silica-alumina hydrate Siral-40, containing 40 wt.% of SiO2, in the composition of a composite cobalt Fischer–Tropsch synthesis (FTS) catalyst was studied. The use of silica aluminas may become a new promising direction in the development of catalysts for a shortened technological chain based on the use of bifunctional catalysts that make it possible to eliminate the hydroprocessing stage. In addition, such catalysts can be useful for expanding the range of products obtained, including those unconventional for single-reactor Fischer–Tropsch synthesis. The initial silica alumina powder was pretreated in air flow at different temperatures to adjust the concentration of acid cites on its surface. The initial and calcined powders were studied using X-ray diffraction analysis, IR spectroscopy and sorption methods. The catalysts were investigated by diffraction and sorption methods. It has been shown that an increase in the calcination temperature of the initial Siral-40 powder leads to a decrease in the specific surface area and pore volume of catalysts based on it, with temperatures above 900 °C having the greatest effect. The synthesized catalysts were active in FTS, and the composition of the obtained C5+ hydrocarbons depended more on the properties of the Siral-40 powder than the catalytic performance. The composition of C5+ hydrocarbons, obtained in the presence of all investigated catalysts contained at least 60% of diesel fraction and more than 30% of wide base oil fraction. Thus, synthetic amorphous silica aluminas are a promising component for new Fischer–Tropsch synthesis catalysts, which make it possible to obtain a wide range of products without the use of a deep hydroprocessing stage in the technological chain. For citation: Sineva L.V., Asalieva E.Yu., Gryaznov K.O., Mordkovich V.Z. Prospects for using a cobalt catalyst for Fisher-Tropsch synthesis based on synthetic silica alumina. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 10. P. 88-98. DOI: 10.6060/ivkkt.20246710.7y.

Phytosterol Depletion in Soybean Oil Using a Synthetic Silica Adsorbent

Phytosterols in vegetable oils have gained attention for their nutritional benefits in foods and food supplements. However, the use of vegetable oils in emulsions for infant formulas and parenteral nutrition has raised some concerns, as phytosterols may contribute to phytosterolemia in the case of infant formulas and, in a second scenario, to parenteral nutrition-associated liver disease. The present study proposes removing phytosterols from soybean oil using a synthetic amorphous silica Trisyl® (E551) as an adsorbent material. The process is simple and involves stirring the oil at a high temperature under vacuum conditions followed by filtration to remove the adsorbent. A rotational factorial design of experiments, considering the adsorbent/oil ratio, temperature, and time was carried out to determine the optimal conditions. Additionally, the effects on tocopherols levels and formation of trans fatty acids were explored. The total sterol content in the initial refined soybean oil was 2540 mg/kg, with 32% in ester form (813 mg/kg). The treatments effectively reduced the sterol concentration, achieving a reduction of nearly 70% when 10% Trisyl®, 140 °C, and a 90-min treatment were applied. Under these conditions, nearly 80% of the oil was recovered. Campesterol and stigmasterol levels were almost halved. Tocopherol losses were found to be below 20%. Thermal degradation, as analyzed by triacylglycerol polymers and trans fatty acids, was not observed in the treatments.

A simulation analysis on the internal and external application of new silica-aerogel-based (Quartzene) coatings effects on energy use in a typical building in two different climates

The study investigates the impact of improved synthetic amorphous silica, specifically developed aerogel-based insulating coatings, Quartzene (Qz), on energy efficiency in buildings across cold and warm climate zones. Simulations were conducted on various coatings and thicknesses for exterior and interior wall surfaces, as well as roofs. These were evaluated using a prototype residential building under dynamic thermal conditions. Wall coatings were analyzed, including a base plaster and a mixture with 10%Wt aerogel-based Quartzene. Additionally, three roof coating samples were tested: Qz 12.5%Wt, TiO2 3.3%Wt, and a blend of aerogel-based mixtures and TiO2. Mixtures containing Qz exhibited the lowest thermal conductivity (0.05 W/(m·K)) and high short-wave reflectance (up to 0.93 μm), impacting transmission loads, time lag, and decrement factor. Energy savings of up to 11% were observed in warm climates when implementing the coatings (unaged performance). Overall, the coated surfaces increased time lag and reduced decrement factor compared to uncoated surfaces. Aerogel-based coatings showed enhanced effectiveness in lowering transmission loads.

P19-71 In vitro screening for immunotoxicity assessment of nanomaterials, a case study using synthetic amorphous silica

P19-71 In vitro screening for immunotoxicity assessment of nanomaterials, a case study using synthetic amorphous silica

Reproduction toxicity study with the synthetic amorphous silica SYLOID® AL-1 FP, HDK® N20, LUDOX® P T-40 F and SYLOID® MX 107 in the earthworm species Eisenia fetida

Ecotoxicology studies were performed in the earthworm Eisenia fetida with four different synthetic amorphous silica (SAS) (SYLOID® AL-1 FP, SYLOID® MX 107, LUDOX® P T-40 F, and HDK® N20) mixed into artificial soil to determine a NOEC/LOEC for effects on reproduction (56 days after application), mortality and biomass development (28 days after application) using a standardized artificial soil with 10% peat. The LC50 for test-item effects on adult mortality, and an EC10 and EC50 for reproduction were also determined. Furthermore, earthworms underwent histopathology evaluation, and the amount of silica in different organs from these organisms was evaluated using EDX (Energy Dispersive X-ray Spectroscopy). Histopathology revealed no findings in any organ of the earthworms, except for desiccated dissepiments in evaluated decedents at extremely high SAS doses. To measure SAS uptake into the organs, a fully quantitative method for silica was established and validated using standards containing known concentrations of silica to ensure the accuracy of the analyses undertaken. Results from EDX analysis demonstrated the negligible presence of silicon within the brain ganglia and gonads of adult earthworms comparable to controls. Therefore, any deposition of the test items within these two organs was excluded. In contrast, traces of silicon higher than in controls were found in the intestinal lumina of the earthworms due to ingestion of SAS with soil and feed, but not in other organs.

Eosinophilic globules (syn. hyaline inclusions) and protein crystalloids in the nasal mucosa of rats treated with synthetic amorphous silica, an unspecific chitinase-like-protein-positive background lesion

In a 13-week inhalation toxicity study with three recovery periods (3, 6, and 12 months), Crl: WI rats were allocated to nine groups, each containing 25 animals per sex. Eight groups were treated daily by inhalation with the test items at concentrations of 0.5, 1.0, 2.5, or 5.0 mg/m3 (SAS 1 groups 2, 3, 4, or 5, respectively; SAS 2 groups 6, 7, 8, or 9, respectively). Controls (group 1) were treated with air only.In nasal cavities, the major lesions consisted of increased eosinophilic globules and chitinase-3-like-protein-positive crystalloids* in the nasal mucosa, mainly in nasal cavity levels 2–4 up to week 26 of recovery without any further injury in olfactory mucosa, mainly in SAS 1-treated animals. Eosinophilic globules in the rodent nasal cavity are common and increase with age; they represent a particular finding of the rodent nasal mucosa. The relevance of chitinase-3-like protein (Ym1 + Ym2) expression in the rodent nasal mucosa is unknown but is normal in control animals. Both findings developed without any indicator for inflammatory processes. The increase of these unspecific background findings is considered an indicator of minor irritative effects.Due to the clear lack of nasal tissue injury or concurrent changes (degeneration, necrosis, inflammatory infiltrate, dysplasia, and/or neoplasia) following repeated inhalation exposure to SAS, it is deemed that the eosinophilic globules (hyaline inclusions) combined with the formation of eosinophilic protein crystalloids in this study represent an adaptive response.

Enhanced study design for acute inhalation studies with hydrophobic surface-treated particles to determine toxicological effects including suffocation

High concentrations of low-density particles may cause effects in acute inhalation toxicity studies which can be easily underestimated or misinterpreted following strictly the OECD TG 436, i.e., limited parameters as mortality and gross lesions will be evaluated only. Seven particle types (synthetic amorphous silica (SAS) HMDZ-SAS, silica gel, pyrogenic SAS, and precipitated SAS, calcium carbonate, aluminum oxide pyrogenic alumina, organic red pigment) were chosen at the highest technically feasible concentration of approximately 500 mg/m3 for acute inhalation studies with an expanded endpoint setup. Therefore additional parameters and a thorough histopathological evaluation of an extensive set of organs, including the respiratory tract emphasizing the nasal cavities were added. Six Crl:WI rats per study were exposed for four hours from which three animals were sacrificed after 24 hours and three animals after 14 days. HMDZ-SAS caused early death in all animals due to blockage of the nasal passages caused by its hydrophobicity. For all other Si-containing compounds, histology revealed minor inflammatory and reactive lesions in lungs after 24 hours that were still present after 14 days, except in silica gel-treated animals. After 14 days, for pyrogenic SAS, precipitated SAS, and pyrogenic alumina, granulomas formed in the BALT and lung-associated lymph nodes. In contrast, the calcium carbonate induced almost no findings, and the red pigment (also tested for the additional dose of 1000 mg/m3) stuck partially to the nasal mucosa without causing pathological damage and partly entered the lungs without showing any adverse effects. The results of the present study highlight the advantage of improving the rather simple study design of acute inhalation studies by implementing an extended study design.

Successful long-term control of poultry red mite (Dermanyssus gallinae) infestations in floor-kept laying hens via integrated pest management—a case report

This case report describes the successful control of poultry red mite [PRM] (Dermanyssus gallinae) infestations in an experimental laying hen house via a combined use of cleaning and disinfection measure, the preventive application of a synthetic silica-based acaricide and frequent mite monitoring. The high number of PRM in the laying hen house was reduced by 99.8% by treatment with fluralaner (Exzolt®, MSD Animal Health Unterschleißheim, Germany; 0.5 mg/kg body weight via drinking water twice, 7 days apart). After the laying hens were removed, the hen house was dry-cleaned, wet-cleaned and disinfected. After drying, synthetic amorphous silica (Fossil Shield® instant white, Bein GmbH, Eiterfeld, Germany) was applied as a preventive measure before the hen house was restocked with pullets for two housing periods of 58 and 52 weeks. Over these periods (i.e. more than 2 years), no PRM was detected during mite monitoring at two-week intervals via tube traps and visual monitoring. This result therefore suggests that the combined use of appropriate chemical and physical prevention measures within an integrated pest management regime can be successfully used for the long-term control of PRM. This could reduce the use of acaricidal drugs, thereby helping maintain their efficacy.

Silica particles convert thiol-containing molecules to disulfides

Synthetic amorphous silica is a common food additive and a popular cosmetic ingredient. Mesoporous silica particles are also widely studied for their potential use in drug delivery and imaging applications because of their unique properties, such as tunable pore sizes, large surfaces areas, and assumed biocompatibility. Such a nanomaterial, when consisting of pure silicon dioxide, is generally considered to be chemically inert, but in this study, we showed that oxidation yields for different compounds were facilitated by simply incubating aqueous solutions with pure silica particles. Three thiol-containing molecules, L-cysteine, glutathione, and D-penicillamine, were studied separately, and it was found that more than 95% of oxidation happened after incubating any of these compounds with mesoporous silica particles in the dark for a day at room temperature. Oxidation increased over incubation time, and more oxidation was found for particles having larger surface areas. For nonporous silica particles at submicron ranges, yields of oxidation were different based on the structures of molecules, correlating with steric hindrance while accessing surfaces. We propose that the silyloxy radical (SiO•) on silica surfaces is what facilitates oxidation. Density functional theory calculations were conducted for total energy changes for reactions between different aqueous species and silicon dioxide surfaces. These calculations identified two most plausible pathways of the lowest energy to generate SiO• radicals from water radical cations H2O•+ and hydroxyl radicals •OH, previously known to exist at water interfaces.

Investigation on the skin penetration of synthetic amorphous silica (SAS) used in cosmetic products

Synthetic amorphous silica (SAS) is used as additive in a variety of industrial applications for many decades and has been approved to be used in food, food contact materials, pharmaceuticals, and cosmetics. Due its internal structure, SAS is considered as a nanomaterial, thus it is affected by a general safety discussion. Based on the production process, SAS for cosmetic application is a nanomaterial by the EU Recommendation, although it was not considered as such, because the solely size-dependent definitions of the term “nanomaterial” emerged in recent times first in Recommendation 2011/696/EU. Therefore, former physicochemical and toxicological evaluations of SAS were already performed on nanomaterials, however, without being addressed as such. Safety concerns can only emerge if two criteria, (toxicological) hazard and exposure towards the substance is fulfilled at the same time. In case of SAS, the Scientific Committee on Consumer Safety (SCCS) challenged provided data to be insufficient to draw a conclusion regarding the safety of SAS and thus, requested further investigations, in particular by exploring skin penetration of particulate SAS.Investigation of specific particulate substances in skin penetration tests is an analytical challenge. The number of available analytical techniques that are capable to detect nanomaterials in complex matrices, like receptor fluids from skin penetration testing, are limited and still emerging. In the new studies, a comprehensive set of analytical techniques were used to investigate the skin penetration potential of SAS. Particle-sensitive, element and particle-specific combinations of techniques and different sample preparation procedures, that respected the particulate nature of SAS, were used to detect SAS in receptor fluids directly. In addition, electron microscopic techniques were used to examine different layers of skin to detect adsorbed SAS.The combination of Asymmetric Flow Field-Flow Fractionation (AF4) in combination with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for examination of receptor fluids and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (SEM/EDX) for examination of skin itself, were identified as suitable techniques for the detection of SAS in skin penetration tests. Data from literature was used to compare the results of the studies with the outcome of other test systems (other particles, other techniques). Both, the test results, and literature evaluation led to the conclusion, that SAS does not penetrate skin. Based on this outcome and local and systemic dermal toxicity review of SAS, it can be concluded that dermal application of SAS in cosmetic formulations is negligible.

Nine human epidemiological studies on synthetic amorphous silica and respiratory health

The respiratory health effects of Synthetic Amorphous Silica (SAS) have been studied in human epidemiological research. This article presents a historical overview and review of nine occupational worker studies that have been conducted so far on this topic. The combined study population of all of these studies included 1172 employees, and exposure concentrations ranged from < 1 mg/m3 to 100 mg/m3. In two studies with a total of 293 workers, the incidence of silicosis was investigated after long-term exposure to precipitated SAS, and no cases of silicosis were found (Plunkett and Dewitt, 1962; Volk, 1960). In another study, the spirometry results of 40 workers were normal (Vitums et al., 1977). In a study of 28 workers, 4 cases of silicosis were identified, but it is possible that contamination with cristobalite occurred and detailed information about the amorphous silica origin was not provided (Mohrmann and Kahn, 1985). Ferch et al. (1987) found that lung impairment was associated with confounding factors (smoking) but not with exposure to precipitated SAS in a study of 143 workers. Choudat et al. (1990) reported a reduction in forced expiratory flow in a group exposed to precipitated SAS compared to a control group. Still, they found no correlation between the extent of exposure and pulmonary function was found in a study of 131 workers. Wilson et al. (1979) also failed to show a significant association between the degree of exposure to precipitated SAS and annual changes in lung function in a study of 165 workers. In the most recent and most extensive study (Taeger et al., 2016; Yong et al., 2022) in Germany, involving 462 factory workers, no association between inhalable or respirable SAS dust exposure and respiratory health was reported. Based on the available data, there is no evidence-base to support a relationship between SAS and respiratory health in humans.

Is pulmonary inflammation a valid predictor of particle induced lung pathology? The case of amorphous and crystalline silicas

Although inflammation is a normal and beneficial response, it is also a key event in the pathology of many chronic diseases, including pulmonary and systemic particle-induced disease. In addition, inflammation is now considered as the key response in standard settings for inhaled particles and a critical endpoint in OECD-based sub-acute/ chronic animal inhalation testing protocols. In this paper, we discuss that whilst the role of inflammation in lung disease is undeniable, it is when inflammation deviates from normal parameters that adversity occurs. We introduce the importance of the time course and in particular, the reversibility of inflammation in the progression towards tissue remodelling and neoplastic changes as commonly seen in rat inhalation studies. For this purpose, we used sub-chronic/ chronic studies studies with synthetic amorphous silicas (SAS) and reactive crystalline silica (RCS) as a source of data to describe the time-course of inflammation towards and beyond adversity. Whilst amorphous silicas induce an acute but reversible inflammatory response, only RCS induces a persistent, progressive response after cessation of exposure, resulting in fibrosis and carcinogenicity in rodents and humans. This suggests that the use of inflammation as a fixed endpoint at the cessation of exposure may not be a reliable predictor of particle-induced lung pathology. We therefore suggest extending the current OECD testing guidelines with a recovery period, that allows inflammation to resolve or progress into altered structure and function, such as fibrosis.

Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS)

Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.

Inhalable Saharan dust induces oxidative stress, NLRP3 inflammasome activation, and inflammatory cytokine release

Desert dust is increasingly recognized as a major air pollutant affecting respiratory health. Since desert dust exposure cannot be regulated, the hazardousness of its components must be understood to enable health risk mitigation strategies. Saharan dust (SD) comprises about half of the global desert dust and contains quartz, a toxic mineral dust that is known to cause severe lung diseases via oxidative stress and activation of the NLRP3 inflammasome-interleukin-1β pathway. We aimed to assess the physicochemical and microbial characteristics of SD responsible for toxic effects. Also, we studied the oxidative and pro-inflammatory potential of SD in alveolar epithelial cells and the activation of the NLRP3 inflammasome in macrophage-like cells in comparison to quartz dusts and synthetic amorphous silica (SAS).Characterization revealed that SD contained Fe, Al, trace metals, sulfate, diatomaceous earth, and endotoxin and had the capacity to generate hydroxyl radicals. We exposed A549 lung epithelial cells and wild-type and NLRP3-/- THP-1 macrophage-like cells to SD, three well-investigated quartz dusts, and SAS. SD induced oxidative stress in A549 cells after 24 h more potently than the quartz dusts. The quartz dusts and SAS upregulated interleukin 8 expression after 4 h and 24 h while SD only caused a transient upregulation. SD, the quartz dusts, and SAS induced interleukin-1β release from wild-type THP-1 cells>20-fold stronger than from NLRP3-/- THP-1 cells. Interleukin-1β release was lower for SD, in which microbial components including endotoxin were heat-destructed.In conclusion, microbial components in SD are pivotal for its toxicity. In the epithelium, the effects of SD contrasted with crystalline and amorphous silica in terms of potency and persistence. In macrophages, the strong involvement of the NLRP3 inflammasome emphasizes the acute and chronic health risks associated with desert dust exposure.

Synthetic amorphous silica: environmental impacts of current industry and the benefit of biomass-derived silica

Life cycle assessment shows the environmental impact of two existing industrial methods for the manufacture of silica and two potential methods using biomass as a feedstock. Processes are then compared with consideration made for model uncertainty.

About the Transient Effects of Synthetic Amorphous Silica: An In Vitro Study on Macrophages.

Silica (either crystalline or amorphous) is widely used for different applications and its toxicological assessment depends on its characteristics and intended use. As sustained inflammation induced by crystalline silica is at the root of silicosis, investigating the inflammatory effects induced by amorphous silicas and their persistence is needed. For the development of new grades of synthetic amorphous silicas, it is also desirable to be able to understand better the factors underlying potential adverse effects. Therefore, we used an optimized in vitro macrophage system to investigate the effects of amorphous silicas, and their persistence. By using different amorphous silicas, we demonstrated that the main driver for the adverse effects is a low size of the overall particle/agglomerate; the second driver being a low size of the primary particle. We also demonstrated that the effects were transient. By using silicon dosage in cells, we showed that the transient effects are coupled with a decrease of intracellular silicon levels over time after exposure. To further investigate this phenomenon, a mild enzymatic cell lysis allowed us to show that amorphous silicas are degraded in macrophages over time, explaining the decrease in silicon content and thus the transiency of the effects of amorphous silicas on macrophages.

Comparison of Biogenic Amorphous Silicas Found in Common Horsetail and Oat Husk With Synthetic Amorphous Silicas.

The present study summarizes the current literature on the presence and the structure of biogenic amorphous silica (BAS) in nature. Based on this review, it is shown that BAS is ubiquitous in nature and exhibits a structure that cannot be differentiated from the structure of synthetic amorphous silica (SAS). The structural similarity of BAS and SAS is further supported by our investigations—in particular, specific surface area (BET) and electron microscope techniques—on oat husk and common horsetail. Many food products containing BAS are considered to be beneficial to health. In the context of the use of SAS in specific applications (e.g., food, feed, and cosmetics), this is of particular interest for discussions of the safety of these uses.

Surface Treatment With Hydrophobic Coating Reagents (Organosilanes) Strongly Reduces the Bioactivity of Synthetic Amorphous Silica in vitro.

Synthetic amorphous silica (SAS) is industrially relevant material whose bioactivity in vitro is strongly diminished, for example, by protein binding to the particle surface. Here, we investigated the in vitro bioactivity of fourteen SAS (pyrogenic, precipitated, or colloidal), nine of which were surface-treated with organosilanes, using alveolar macrophages as a highly sensitive test system. Dispersion of the hydrophobic SAS required pre-wetting with ethanol and extensive ultrasonic treatment in the presence of 0.05% BSA (Protocol 1). Hydrophilic SAS was suspended by moderate ultrasonic treatment (Protocol 2) and also by Protocol 1. The suspensions were administered to NR8383 alveolar macrophages under serum-free conditions for 16 h, and the release of LDH, GLU, H2O2, and TNFα was measured in cell culture supernatants. While seven surface-treated hydrophobic SAS exhibited virtually no bioactivity, two materials (AEROSIL® R 504 and AEROSIL® R 816) had minimal effects on NR8383 cells. In contrast, non-treated SAS elicited considerable increases in LDH, GLU, and TNFα, while the release of H2O2 was low except for CAB-O-SIL® S17D Fumed Silica. Dispersing hydrophilic SAS with Protocol 1 gradually reduced the bioactivity but did not abolish it. The results show that hydrophobic coating reagents, which bind covalently to the SAS surface, abrogate the bioactivity of SAS even under serum-free in vitro conditions. The results may have implications for the hazard assessment of hydrophobic surface-treated SAS in the lung.

A Systematic Review on the Hazard Assessment of Amorphous Silica Based on the Literature From 2013 to 2018.

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

Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS).

The aim of the present study was to understand the mechanism of lethality associated with high dose inhalation of a low-density hydrophobic surface-treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract (nasal cavities) caused the effects observed. Hydrophobic surface-treated SAS was inhaled (flow-past, nose-only) by six Wistar rats (three males and three females) in an acute toxicity study at a concentration of ~500 mg/m3 for an intended 4-hr exposure. Under the conditions of the test set-up, the concentration applied was found to be the highest that can be delivered to the test animal port without significant alteration of the aerosol size distribution over time. None of the test- material-exposed animals survived the planned observation time of 4 h; three animals died between 2 h after starting exposure and cessation of exposure at 3 h, two died after transfer to their cages and the remaining animal was sacrificed due to its poor condition and welfare considerations. Histology accomplished by energy dispersive X-ray (EDX) analysis demonstrated that test material particles agglomerated and formed a gel-like substrate that ultimately blocked the upper respiratory airways, which proved fatal for the rat as an obligatory nose breather. This observation is in line with the findings reported by Hofmann et al. showing a correlation between lethality and hydrophobicity determined by contact angle measurement. The aerosol characterizations associated with this study are provided in detail by Wessely et al.