Physicochemical Properties
| Molecular Formula | O2SI |
| Exact Mass | 59.966 |
| CAS # | 112945-52-5 |
| Related CAS # | 31392-49-1 |
| PubChem CID | 24261 |
| Appearance |
Amorphous powder Transparent to gray powder (Note: Amorphous silica is the non-crystalline form of O2Si). ... solid Silica gel is a coherent, rigid, continuous three-dimensional network of spherical particles of colloidal microporous silica. Transparent crystals |
| Density | 2.3 lb/cu.ft at 25 °C (bulk density)(lit.) |
| Boiling Point | 2230ºC |
| Melting Point | >1600°C |
| Index of Refraction | n20/D 1.46(lit.) |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 3 |
| Complexity | 18.3 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [Si](=O)=O |
| InChi Key | VYPSYNLAJGMNEJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/O2Si/c1-3-2 |
| Chemical Name | dioxosilane |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion ...Rats /were exposed/ by inhalation to... silica (particle size 0.5 to 5 m) in the form of Belgian glass sand for periods ranging from 0.5 to 40 hr. The initial deposition of silica was highest in the tracheobronchial ciliated air passages; it also was seen throughout the acini, where the extent of deposition decreased as the respiratory airways proceeded distally. The distribution of particles was not uniform between the different acini, and, 2 to 3 months following cessation of exposure, aggregates were formed, primarily in the proximal alveolar ducts but also in the distal portion of the acini. Inhalation studies with rats... indicate that the long-term clearance of quartz after inhalation is slow and biphasic, whereas amorphous silica dusts are cleared more rapidly. The absolute amount of silica dust eliminated increased with lung burden, but the efficiency of the elimination was either constant or decreased with time. ...The half-life lung clearance of rats exposed via inhalation to an amorphous silica suspension (Ludox ) at concentrations up to 150 mg/cu m was about 50 days. A study /in (1983)/, showed that the total silica content in the lungs of guinea pigs exposed by inhalation for up to 2 years to a cristobalite sample or to amorphous silica (at dust concentrations of 150 mg/cu m or 100 mg/cu m , respectively) increased linearly over 21 months, without evidence that lung retention rates changed with time. ...The maximum lung content of cristobalite was only 68 mg/lung, whereas that of amorphous silica was 120 mg/lung. The total amount of accumulated silica varied inversely with the degree of pulmonary damage. /It was/ suggested that silica dust producing cell damage may be more efficiently cleared from the lung than are the less toxic amorphous forms. However, this difference also could be due to different rates of deposition for the two dust forms. The cristobalite sample, which was 45% cristobalite and 55% diatomaceous earth, was significantly coarser (and less likely to deposit in the lungs) than the amorphous silica, which contained 100% diatomaceous earth. Also, tissue changes induced by cristobalite could have altered particle deposition. In a long-term inhalation study with guinea pigs, ...the amount of silica retained as a result of 8-hr/day exposures to amorphous silica (Hi-Sil 233) /was compared/ with that retained during inhalation of quartz dust for a comparable 12-month period. Guinea pigs that inhaled quartz dust at a concentration of 106 mg/cu m retained between 500 and 600 mg of silica, whereas <10 mg of dust was retained in those that inhaled 126 mg/cu m of amorphous silica. After 12 months of exposure, the relative silica content (silica mass/lung mass) decreased in guinea pigs exposed to quartz dust, but continued to increase slowly in the animals exposed to the amorphous silica. This difference was explained by an increasing nonsiliceous materials content (e.g., collagen, minerals) in the lungs of the quartz-exposed animals associated with the progressive deposition of fibrous tissue in the lungs. Six months after cessation of exposure, the silica content of the lungs of Hi-Sil 233-exposed animals was similar to that of untreated controls. This lack of accumulation may be due, in large part, to the higher solubility of amorphous silica compared to quartz... . By comparison, the elimination of silica from the quartz-exposed guinea pigs was negligible, and the silicotic lesions continued to progress during this elimination phase. For more Absorption, Distribution and Excretion (Complete) data for AMORPHOUS SILICA (6 total), please visit the HSDB record page. Rats were exposed for 6 hr/day, on 5 days/week, for up to 13 weeks to 3 mg/cu m crystalline... Lung burdens were 819... ug for crystalline... Deposition of particles in the respiratory bronchioles and proximal alveoli results in slow clearance, interaction with macrophages and a greater likelihood of lung injury. This contrasts with deposition on the conducting airways where the majority of the particles are cleared by the mucociliary escalator. Therefore, quartz particles with an aerodynamic diameter below 10 um are likely to be the most harmful to humans. There are few data on human lung quartz-dust burdens that allow conclusions to be drawn about deposition or clearance. However, quartz is found in the bronchoalveolar macrophages and sputum of silicotic patients. Also, at autopsy, there is wide variation in the masses and proportions of quartz retained in the lung. For example... 25-264 mg /were reported/ per single lung at autopsy in hard-rock miners with 14-36 years of exposure; these miners had variable amounts of pathological response but there was not a good correlation between lung crystalline quartz content and pathological score. The well-documented effect of smoking on clearance is a further confounding factor in drawing conclusions about clearance kinetics in humans. The physico-chemical changes in quartz that result from residence in the lung could be an important factor in determining the continuing toxicity of quartz to the lung following deposition. As a response to the rejection of the 'mechanical model' of silicosis, which had propounded that any particle with 'sharp or jagged edges' might injure tissue, a solubility theory of silicosis was proposed. The solubility theory was based on the release from silica of silicic acid, which was considered to be a 'protoplasmic poison.' In fact very little dissolution occurs; for example, 9 mg SiO2 (0.45%) was released from 2 g crystalline silica placed in ascitic fluid for two weeks. Current theories no longer consider that the dissolution of quartz contributes substantially to its clearance or to changes in its biological activity. Indeed there is evidence of enrichment of crystalline silica in lungs of individuals exposed to hard rock compared to the dust in the air they breathed, suggesting that crystalline silica is less-efficiently cleared, either by dissolution or mechanical clearance, than the non-silica mineral components of the dust... biopersistence was assessed in occupationally exposed subjects by counting silica particles in bronchoalveolar lavage (BAL) fluid after varying periods of time since their last occupational exposure. Crystalline silica was found to be among the most biopersistent of non-fibrous mineral particles. For more Absorption, Distribution and Excretion (Complete) data for CRYSTALLINE SILICA (17 total), please visit the HSDB record page. |
| References |
[1]. Pharmaceutical excipients - quality, regulatory and biopharmaceutical considerations. Eur J Pharm Sci. 2016 May 25;87:88-99. |
| Additional Infomation |
Silica is another name for the chemical compound composed of silicon and oxygen with the chemical formula SiO2, or silicon dioxide. There are many forms of silica. All silica forms are identical in chemical composition, but have different atom arrangements. Silica compounds can be divided into two groups, crystalline (or c-silica) and amorphous silica (a-silica or non-crystalline silica). c-Silica compounds have structures with repeating patterns of silicon and oxygen. a-Silica chemical structures are more randomly linked when compared to c-silica. All forms of silica are odorless solids composed of silicon and oxygen atoms. Silica particles become suspended in air and form non-explosive dusts. Silica may combine with other metallic elements and oxides to form silicates. Transparent to gray, odorless powder. Irritating to the skin and eyes on contact. Inhalation will cause irritation in the respiratory tract. [Note: Amorphous silica is the non-crystalline form of SiO2.] Silicon dioxide is a silicon oxide made up of linear triatomic molecules in which a silicon atom is covalently bonded to two oxygens. Silicon dioxide, or silica, is an oxide of silicon with the chemical formula SiO2. It is found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite as transparent and tasteless crystals. Inhalation of fine crystals is toxic to humans leading to respiratory toxicity. In powdered food products and pharmaceutical tablets, silicon dioxide is added as a flow agent to absorb water. Colloidal silica is also used as a wine, beer, and juice fining agent or stabilizer. Silicon Dioxide has been reported in Equisetum arvense, Phyllostachys edulis, and other organisms with data available. Silicon Dioxide is a natural compound of silicon and oxygen found mostly in sand, Silica has three main crystalline varieties: quartz, tridymite, and cristobalite. Fine particulate silica dust from quartz rock causes over a long-term progressive lung injury, silicosis. (NCI04) Coesite is a mineral with formula of SiO2. The corresponding IMA (International Mineralogical Association) number is IMA1962 s.p.. The IMA symbol is Coe. Cristobalite is a mineral with formula of SiO2. The IMA symbol is Crs. See also: Meloxicam (active moiety of); Quartz (has subclass); Tridymite (has subclass) ... View More ... Mechanism of Action ...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and oxygen consumption support the conclusion that ROS are generated by silica-treated cells. N-Acetylcysteine (an antioxidant) and polyvinyl pyridine-N-oxide (an agent that binds to Si-OH groups on silica surfaces) decreased AP-1 activation and phosphorylation of ERKs and p38 kinase. Catalase inhibited phosphorylation of ERKs and p38 kinase, as well as AP-1 activation induced by FFSi, suggesting the involvement of H2O2 in the mechanism of silica-induced AP-1 activation. Sodium formate (an OH /radical/ scavenger) had no influence on silica-induced MAPKs or AP-1 activation. Superoxide dismutase enhanced both AP-1 and MAPKs activation, indicating that H2O2, but not O2, may play a critical role in silica-induced AP-1 activation. These studies indicate that freshly ground silica is more biologically active than aged silica and that ROS, in particular H2O2, play a significant role in silica-induced AP-1 activation. /The authors/ examined the involvement of oxidative stress and reactive oxygen species formation in silica-induced cytotoxicity and genotoxicity in cultured rat /alveolar macrophages/ AMs. A lucigenin-dependent chemiluminescence test was used to determine superoxide anion... and a 2',7'-dichlorofluorescin diacetate fluorescence test was employed to measure the hydrogen peroxide (H2O2) level. The cytotoxic and genotoxic effects caused by silica in AMs were examined by lactate dehydrogenase (LDH) leakage and single-cell gel electrophoresis (comet assay), respectively. The results showed that silica enhanced superoxide and H2O2 formation in AMs. There were clear dose- and time-dependent relationships in silica-induced cytotoxicity and genotoxicity. Furthermore, superoxide dismutase and catalase were able to reduce silica-induced LDH leakage and DNA damage, with concurrent significant inhibition on silica-induced oxidative stress in AMs. These findings provide convincing evidence that oxidative stress mediates the silica-induced cytotoxicity and genotoxicity. For more Mechanism of Action (Complete) data for CRYSTALLINE SILICA (32 total), please visit the HSDB record page. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |