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Structural model of silica nanowire assembled from a highly stable (SiO2)8 unit.

The ground-state structures of silica clusters (SiO2)n for n = 1-8 were studied by performing calculations at the B3LYP/6-311+G(d) level of density functional theory. The results indicate that the growth mode of a silica nanowire based on small silica clusters may change at different wire lengths. A linear chain might be assembled from the smallest clusters of rhombic two-membered ring (2MR) with n < or = 5, while the growth motif changes at n = 6 into a more compact form composed of three-membered-rings (3MRs). The 3MR-containing structures become energetically favorable configurations for even longer silica clusters. In particular, the closed molecular ring consisting of 3MRs at n = 8 (i.e., (SiO2)8) with a high symmetry shows extreme energetic stability and relatively high chemical reactivity and thus is considered to be an important building block to assemble into silica nanowires. The relative stability of so-assembled silica nanowires were evaluated and compared with the models of silica nanowires in the literature.

Journal Article↗

Density functional theory study of geometrical structures and electronic properties of silica nanowires.

Silica nanowires are expected to possess structural diversity like bulk silica. We modeled three silica nanowires based on the side-shared two-membered rings, spiro-united two-membered rings, and three-membered rings, respectively. By performing density functional theory calculations, we studied their geometrical structures and electronic properties with and without the presence of external electric field. It is found that the stability of silica nanowires increases with length and diameter. As indicated by calculated large HOMO-LUMO gaps, silica nanowires are expected to be good insulating materials. The energy gaps, however, gradually decrease with applied electronic field and finally close, resulting in the breakdown of the insulating nanowires. Moreover, it is shown that the breakdown threshold remarkably increases with the nanowire diameter. These significant findings from the present calculations for the simplest silica nanowires will provide relevant insight into the structures and properties of much more complicated real silica nanowires.

Letter↗

Surface patterning of silica nanostructures using bio-inspired templates and directed synthesis.

Natural systems excel in directing the synthesis of inorganic materials for various functional purposes. One of the best-studied systems is silica synthesis, as occurs in diatoms and marine sponges. Various biological and synthetic polymers have been shown to template and catalyze silica formation from silicic acid precursors. Here, we describe the use of poly-L-lysine to promote the synthesis of silica in neutral, aqueous solution and when immobilized onto a silicon support structure under similar conditions. Either reagent jetting or conventional photolithography techniques can be used to pattern the templating polymer. Spots created by reagent jetting led to the creation of silica structures in the shape of a ring that may be a result of the spotting process. Photolithographically defined poly-L-lysine spots led to thin laminate structures after exposure to a dilute aqueous silicic acid solution. The laminate structures were nanostructured and highly interconnected. Photolithographic patterning of (3-aminopropyl)trimethoxysilane, a reagent that mimics the lysine functional group, led to similar silica coatings even though low-molecular-weight materials do not rapidly promote silica synthesis in solution. This result highlights the importance of functional-group arrangement for templating and promoting the synthesis of inorganic materials. The described surface-patterning techniques offer a route to integrate conventional silicon-patterning technologies with biologically based material synthesis. Such combined fabrication techniques enable controlled assembly over multiple length scales and an approach to understanding interfacial silica synthesis, as occurs in natural systems.

Biomimetics↗

Biomimetic particles: optimization of phospholipid bilayer coverage on silica and colloid stabilization.

The effect of ionic strength and pH on phosphatidylcholine (PC) adsorption from vesicles on silica nanoparticles was investigated over a range of NaCl concentrations (0.1-150 mM) at pH 6.3 and 7.4 from determination of adsorption isotherms, colloid stability, particle sizing, and zeta-potentials. At and above 10 mM ionic strength, pH 6.3, high-affinity adsorption isotherms with limiting adsorption indicative of one-bilayer deposition on each silica particle were obtained. At 10 mM ionic strength, adsorption isotherms indicated lower affinity between PC and silica at pH 7.4 than at pH 6.3, suggesting a role of hydrogen bonding between silanol on silica and phosphate on PC in promoting bilayer deposition at low pH. Under conditions where high affinity and bilayer deposition were achieved, silica sedimentation documented from photographs was absent, suggesting particle stabilization induced by bilayer coverage. However, at physiological (150 mM NaCl) or close to physiological ionic strength (140 mM NaCl), the large colloid stability similarly achieved at pH 6.3 or 7.4 suggested the major role of van der Waals attraction between the PC bilayer vesicle and silica particle in determining bilayer deposition. The effect of increasing ionic strength was increasing van der Waals attraction, which caused PC vesicle disruption with bilayer deposition and bilayer-induced silica stabilization.

Adsorption↗

Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study.

OBJECTIVES: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure-response data. We have conducted a pooled exposure-response analysis of 10 silica-exposed cohorts to investigate lung cancer. METHODS: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1,072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. RESULTS: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0. 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1-1.7%, above background risks of 3-6%. CONCLUSIONS: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies.

Air Pollutants, Occupational↗

Biomimetic synthesis of ordered silica structures mediated by block copolypeptides.

In biological systems such as diatoms and sponges, the formation of solid silica structures with precisely controlled morphologies is directed by proteins and polysaccharides and occurs in water at neutral pH and ambient temperature. Laboratory methods, in contrast, have to rely on extreme pH conditions and/or surfactants to induce the condensation of silica precursors into specific morphologies or patterned structures. This contrast in processing conditions and the growing demand for benign synthesis methods that minimize adverse environmental effects have spurred much interest in biomimetic approaches in materials science. The recent demonstration that silicatein-a protein found in the silica spicules of the sponge Tethya aurantia--can hydrolyse and condense the precursor molecule tetraethoxysilane to form silica structures with controlled shapes at ambient conditions seems particularly promising in this context. Here we describe synthetic cysteine-lysine block copolypeptides that mimic the properties of silicatein: the copolypeptides self-assemble into structured aggregates that hydrolyse tetraethoxysilane while simultaneously directing the formation of ordered silica morphologies. We find that oxidation of the cysteine sulphydryl groups, which is known to affect the assembly of the block copolypeptide, allows us to produce different structures: hard silica spheres and well-defined columns of amorphous silica are produced using the fully reduced and the oxidized forms of the copolymer, respectively.

Cysteine↗

Hydration forces between silica surfaces: experimental data and predictions from different theories.

Silica is a very interesting system that has been thoroughly studied in the last decades. One of the most outstanding characteristics of silica suspensions is their stability in solutions at high salt concentrations. In addition to that, measurements of direct-interaction forces between silica surfaces, obtained by different authors by means of surface force apparatus or atomic force microscope (AFM), reveal the existence of a strong repulsive interaction at short distances (below 2 nm) that decays exponentially. These results cannot be explained in terms of the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, which only considers two types of forces: the electrical double-layer repulsion and the London-van der Waals attraction. Although there is a controversy about the origin of the short-range repulsive force, the existence of a structured layer of water molecules at the silica surface is the most accepted explanation for it. The overlap of structured water layers of different surfaces leads to repulsive forces, which are known as hydration forces. This assumption is based on the very hydrophilic nature of silica. Different theories have been developed in order to reproduce the exponentially decaying behavior (as a function of the separation distance) of the hydration forces. Different mechanisms for the formation of the structured water layer around the silica surfaces are considered by each theory. By the aid of an AFM and the colloid probe technique, the interaction forces between silica surfaces have been measured directly at different pH values and salt concentrations. The results confirm the presence of the short-range repulsion at any experimental condition (even at high salt concentration). A comparison between the experimental data and theoretical fits obtained from different theories has been performed in order to elucidate the nature of this non-DLVO repulsive force.

Journal Article↗

Identification of proteins from a cell wall fraction of the diatom Thalassiosira pseudonana: insights into silica structure formation.

Diatoms are unicellular eucaryotic algae with cell walls containing silica, intricately and ornately structured on the nanometer scale. Overall silica structure is formed by expansion and molding of the membrane-bound silica deposition vesicle. Although molecular details of silica polymerization are being clarified, we have limited insight into molecular components of the silica deposition vesicle, particularly of membrane-associated proteins that may be involved in structure formation. To identify such proteins, we refined existing procedures to isolate an enriched cell wall fraction from the diatom Thalassiosira pseudonana, the first diatom with a sequenced genome. We applied tandem mass spectrometric analysis to this fraction, identifying 31 proteins for further evaluation. mRNA levels for genes encoding these proteins were monitored during synchronized progression through the cell cycle and compared with two previously identified silaffin genes (involved in silica polymerization) having distinct mRNA patterns that served as markers for cell wall formation. Of the 31 proteins identified, 10 had mRNA patterns that correlated with the silaffins, 13 had patterns that did not, and seven had patterns that correlated but also showed additional features. The possible involvements of these proteins in cell wall synthesis are discussed. In particular, glutamate acetyltransferase was identified, prompting an analysis of mRNA patterns for other genes in the polyamine biosynthesis pathway and identification of those induced during cell wall synthesis. Application of a specific enzymatic inhibitor for ornithine decarboxylase resulted in dramatic alteration of silica structure, confirming the involvement of polyamines and demonstrating that manipulation of proteins involved in cell wall synthesis can alter structure. To our knowledge, this is the first proteomic analysis of a diatom, and furthermore we identified new candidate genes involved in structure formation and directly demonstrated the involvement of one enzyme (and its gene) in the structure formation process.

Acetyltransferases↗

Effects of silica exposure on substance P immunoreactivity and preprotachykinin mRNA expression in trigeminal sensory neurons in Fischer 344 rats.

Trigeminal sensory neurons innervate the nasal cavity and may release substance P (SP) upon exposure to inhaled irritants. The purpose of this study was to determine if silica dust, an occupational irritant causing inflammation, activates sensory neurons supplying the nasal cavity. Male Fischer 344 rats were placed in inhalation chambers and exposed daily to 2 mg/m3 of fresh silica (average diameter 1 microm) for 6 mo. Following exposure, the trigeminal ganglia (TG) were removed and prepared for SP immunocytochemistry and for preprotachykinin (PPT) autoradiographic in situ hybridization. The SP-like immunofluorescence in TG neurons was subjectively categorized as high, moderate, or low (background) intensity. In situ hybridization autoradiographs were quantified on the basis of grain density using digital imaging analysis. The SP immunoreactivity and PPT mRNA expression in the TG neurons were significantly increased after silica inhalation. The proportion of highly positive SP-immunoreactive neurons shifted from 1.30 +/- 0.58% in controls to 11.30 +/- 1.15% after silica treatment. The neurons exhibiting high grain density for PPT mRNA increased from 1.50 +/- 0.87% in controls to 11.67 +/- 0.58% in the silica group. Thus, inhalation of silica causes upper airway irritation resulting in increased levels of immunoreactive neuronal SP and PPT mRNA. These findings suggest that silica activates sensory pathways that may be involved in nasal inflammation.

Air Pollutants↗

Time course of pulmonary response of rats to inhalation of crystalline silica: NF-kappa B activation, inflammation, cytokine production, and damage.

In vitro studies suggest that silica-induced lung disease may be linked to processes regulated by nuclear factor-kappa B (NF-kappa B) activation, but this has not been examined in vivo. Rats were exposed to a silica aerosol of 15 mg/m(3) (6 h/day, 5 days/wk) for 116 days, and bronchoalveolar lavage (BAL) was conducted at various times during the exposure. Silica-induced pulmonary inflammation and damage were determined by measuring BAL cell differentials and first BAL fluid lactate dehydrogenase (LDH) activity and serum albumin concentrations, respectively. NF-kappa B activation and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) by BAL cells were also measured. The results demonstrate that NF-kappa B activation occurred after 5 days exposure, and continued to increase thereafter. BAL cell production of IL-1 and TNF-alpha had increased incrementally by 10 and 30 days of exposure, respectively. This elevation continued through 79 days of exposure before further increasing at 116 days of exposure. Pulmonary inflammation and damage in silica-exposed rats were also significantly elevated at 5 days of exposure, further increased at a slow rate through 41 days of exposure, and dramatically increased thereafter. Taken together, the results indicate that the initial molecular response of NF-kappa B activation in BAL cells occurs in response to low levels of silica deposition in the lung and increases more rapidly versus exposure duration than silica-induced pulmonary inflammation, cellular damage, and cytokine production by BAL cells. This suggests that NF-kappa B activation in BAL cells may play an important role in the initiation and progression of silica-induced pulmonary inflammation, cellular damage, and fibrosis.

Animals↗

Regulatory implications of airborne respirable free silica variability in underground coal mines.

The respirable dust standard for respirable free crystalline silica in underground coal mines is expressed as milligrams per cubic meter (mg/m3) of respirable dust and is determined by the silica content of the dust. The Mine Safety and Health Administration (MSHA) regulates silica exposure by determining and enforcing compliance with the respirable dust standard for each active mine section. The MSHA strategy for regulation is examined in the context of respirable free crystalline silica and dust data. Deficiencies of the strategy include the same enforcement efforts regardless of compliance history, inappropriate treatment of data, and emphasis on short-term variability of silica content. These deficiencies result in inadequate enforcement in chronically dusty mines, "game playing" with optional samples, and an overall approach that does not focus on the long-term impact of silica exposure on lung health. Alternative approaches include enforcement efforts proportional to compliance history, use of a moving average silica content, and more statistically sound approaches to data interpretation.

Air Pollutants, Occupational↗

Comparison of coal mine dust size distributions and calibration standards for crystalline silica analysis.

Since 1982 standard calibration materials recommended for respirable crystalline silica analysis by the Mine Safety and Health Administration (MSHA) P7 Infrared Method and the National Institute for Occupational Safety and Health (NIOSH) X-ray Diffraction (XRD) Analytical Method 7500 have undergone minor changes in size distribution. However, a critical assumption has been made that the crystalline silica in ambient mine atmosphere respirable dust samples has also remained essentially unchanged in particle size distribution. Therefore, this work compared recent particle size distributions of underground coal mine dust and the silica component of these dusts with estimated aerodynamic particle size distributions of calibration standard materials MIN-U-SIL 5, Berkeley 5, and SRM 1878 used by two crystalline silica analysis techniques. Dust impactor sampling data for various locations in 13 underground coal mines were analyzed for the respirable mass median aerodynamic diameters. The data suggest that the MSHA P7 method will underestimate the silica content of the sample by at most 7.4% in the median size range 0.9 to 3.6 microm, and that it is unlikely one would obtain any significant error in the MSHA P7 method analysis when the method uses Berkeley 5, MIN-U-SIL 5, or SRM 1878 as a calibration standard material. The results suggest that the NIOSH Analytical Method 7500 would be more appropriate for a dust sample that is representative of the total (no cyclone classifier) rather than the respirable airborne dust, particularly because the mass fraction in the size range below 4 microm is usually a small percentage of the total airborne dust mass. However, NIOSH Analytical Method 7500 is likely to underestimate the silica content of an airborne respirable dust sample by only 5 to 10%. The results of this study also suggest that any changes that may have occurred in the median respirable size of airborne coal mine dust are not significant enough to cause any appreciable error in the current methods used for respirable crystalline silica analysis.

Coal↗

An examination of the cytotoxic effects of silica on macrophages.

Effects of silica, diamond dust, and carrageenan on mouse macrophages were studied by phase-contrast cine-micrography, electron microscopy, histochemical techniques for lysosomal enzymes and measurements of the release of lysosomal enzymes into the culture medium. All added materials were rapidly taken up into phagosomes, to which lysosomes became attached. In all cases lysosomal enzymes were discharged into the phagosomes to form secondary lysosomes. Within 24 hr most of the silica particles and enzyme had escaped from the secondary lysosomes and lysosomal enzymes were found in the culture media. Most macrophages were killed by this time. With nontoxic particles (diamond dust, aluminium-coated silica, or silica in the presence of the protective agent polyvinyl-pyridine-N-oxide, PVPNO) ingested particles and lysosomal enzymes were retained within the secondary lysosomes for a much longer time, and cytotoxic effects were considerably delayed or absent altogether. It is concluded that silica particles are toxic because they are efficiently taken up by macrophages and can then react relatively rapidly with the membranes surrounding the secondary lysosomes. The particles and lytic enzymes can then escape into the cytoplasm, producing general damage, and thence into the culture medium. It is suggested that hydrogen bonding of silicic acid with lipid and protein constituents of the membrane accounts for the induced permeability. Protective agents such as PVPNO are retamed in lysosomes and preferentially form hydrogen bonds with silicic acid. Carrageenan is demonstrable within macrophages by its metachromatic reaction. It brings about release of enzymes from secondary lysosomes, but much more slowly than does silica. Silica released from killed macrophages is as cytotoxic as the original preparation. It is suggested that repeated cycles of macrophage killing in vivo leads to the mobilization of fibroblasts and fibrogenesis characterizing the disease silicosis.

Animals↗

Respirable crystalline silica dust exposure during concrete finishing (grinding) using hand-held grinders in the construction industry.

Studies reporting the findings of exposure to crystalline silica dust during concrete finishing in construction settings are scarce due to the dynamic nature of the activity and the existence of many confounding factors. This study was initiated to explore the issue. A total of 49 personal respirable dust samples were collected during concrete finishing while workers used hand-held grinders. Only 15 (31%) of the grinders were equipped with local exhaust ventilation (LEV) systems. The confounding factors (e.g. wind velocity, wind direction, relative humidity and ambient temperature) were determined. To make the sampling task-specific, air sampling was activated only during actual grinding. Task-specific sampling times during each work shift ranged from 10 to 200 min. The concentration of total respirable particulate ranged from 0.34 to 81 mg/m3, with a mean +/- SD of 18.6 +/- 20.4 mg/m3, and the concentration of crystalline silica in the samples ranged from 0.02 to 7.1 mg/m3, with a mean +/- SD of 1.16 +/- 1.36 mg/m3. LEV on the grinders reduced the silica dust level significantly (P < 0.01) compared to grinders without LEV. Increased wind velocity also reduced the silica dust concentration significantly (P < 0.03). Working upwind reduced the exposure to silica dust compared to working downwind, but the difference was not statistically significant. The time-weighted average concentration of silica dust in 69% of the samples exceeded the current recommended threshold limit value of 0.05 mg/m3, indicating a strong need to devise methods for controlling workers' exposure to crystalline silica dust during concrete finishing activities.

Air Movements↗

Correcting tritium concentrations in water vapor monitored with silica gel.

A correction is needed to calculate the activity concentration of airborne tritium oxide when dried silica gel is used as the collector. A tracer study using tritiated water with silica gel showed that the concentration of tritium in desorbed water is lower than that in adsorbed water by a fraction that increases with the amount of adsorbed water. The hypothesis was tested that adsorbed tritiated water is diluted by isotopic exchange with both non-tritiated water and hydroxyl groups within the silica gel matrix. The extent of dilution was measured from 4% to 14% adsorbed water, which is typical of moisture on field collectors for monitoring airborne tritium oxide. For this range of percent adsorbed water, the inferred percent exchangeable water in the silica gel under study was 6.3 +/- 0.1%. This value compares to the silica gel weight loss of 5.3% after heating to 1,050 degrees C. An explanation of the difference between 6.3% and 5.3% is proposed. The contribution of the HTO/H2O vapor pressure isotope effect was considered in calculating isotopic exchange. A curve is presented for correcting the measured tritium concentration in the distillate from the silica gel as a function of the amount of adsorbed water. The tritium tracer procedure is recommended for determining the percent exchangeable water in other silica gels to correct tritium measurements of water vapor collected by them.

Humans↗

Occupational exposure to crystalline silica and risk of lung cancer: a multicenter case-control study in Europe.

BACKGROUND: The role of crystalline silica dust as a possible cause of lung cancer has been controversial. Relatively few large community-based studies have been conducted to investigate the lung cancer risk from exposure to silica at low levels, taking into account potential confounding factors. METHODS: Detailed lifestyle and occupational information were collected from 2852 newly diagnosed cases of lung cancer and 3104 controls between 1998 and 2002 in 7 European countries. For each job held, local experts assessed the probability, intensity, and duration of silica exposure. RESULTS: Occupational exposure to crystalline silica was associated with an increased risk of lung cancer (odds ratio = 1.37; 95% confidence interval = 1.14-1.65). This risk was most apparent for the upper tertile of cumulative exposure (OR = 2.08; 95% CI = 1.49-2.90; P for trend <0.0001), duration of exposure (1.73; 1.26-2.39; P for trend = 0.0001) and weighted duration of exposure (1.88; 1.35-2.61; P for trend <0.0001). We did not observe any interaction beyond a multiplicative model between tobacco smoking and silica exposure. CONCLUSIONS: Our results support the hypothesis that silica is an important risk factor for lung cancer. This risk could not be explained by exposure to other occupational carcinogens or smoking, and it was present for the main histologic types of lung cancer, different sources of silica exposure, and different industrial settings.

Adenocarcinoma↗

Antimyeloperoxidase antibodies in individuals with occupational exposure to silica.

OBJECTIVE: To determine the prevalence of autoantibodies to myeloperoxidase (MPO) in a series of patients exposed to silica. METHODS: The study included 52 patients with occupational exposure to silica (mean exposure time seven years) and a control group comprising seven patients with progressive systemic sclerosis (PSS), six patients with systemic lupus erythematosus (SLE), and 15 healthy individuals. Antibodies to MPO were detected using commercial enzyme linked immunosorbent assay (ELISA) plates coated with MPO. Indirect immunoflurescence studies for antineutrophil cytoplasmic antibodies were performed using ethanol and formol fixed neutrophils. Clinical and biological data of individuals exposed to silica were recorded (published previously). RESULTS: Antibodies to MPO were detected in 14 individuals exposed to silica (27%). There was a statistically significant difference in anti-MPO ELISA units between the healthy subjects and patients (SLE, PSS, silica exposed individuals) (p < 0.01), but no difference between the different disease groups. CONCLUSIONS: Individuals chronically exposed to silica, whether or not they have a connective tissue disease, have levels of antibodies to MPO (as detected by ELISA) that are greater than those found in the normal population, but similar to those in patients with systemic diseases not induced by silica (SLE/PSS).

Antibodies, Antineutrophil Cytoplasmic↗

Silica, hyaluronate, and alveolar macrophage functional differentiation.

BACKGROUND: Silicosis is mediated by macrophages, their soluble mediators, and extracellular matrix molecules. In this study, we investigated the effects of silica and/or hyaluronate (HA) on several alveolar macrophage responses. METHODS: We evaluated glycosaminoglycan (GAG) production by radiolabeled precursors, nitric oxide (NO) release by its oxidation product, phagocytic activity by Candida albicans internalization, and the secretion of two fibrogenic cytokines, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta, by specific assays. RESULTS: Silica significantly reduced GAG secretion, particularly HA secretion. Alone, it decreased Candida uptake; associated with HA, it enhanced the reduction. Silica and Candida reduced NO release, which was not significantly affected when silica- or Candida-exposed cells were also treated with HA. TNF-alpha and TGF-beta activities were stimulated by silica but reduced by HA. CONCLUSIONS: The results suggest that silica and HA modify alveolar macrophage functional differentiation. Silica- and HA-induced modifications of the microenvironment could determine whether the response proceeds toward healing and repair or toward lung chronic pathology.

Animals↗