The severity of the biological effects of silicon dioxide is strongly dependent on the structure of the material, i.e. whether it is crystalline or amorphous. The size of the particles, whether micro- or nanometer, plays only a minor role. Inhalation of crystalline silica causes considerable inflammation in the lung tissue; amorphous silica, on the other hand, triggers a brief inflammation in high doses, but after it subsides, no further effects occur.
Uptake via the Lung – Inhalation
Silica has either an amorphous or crystalline structure, which has a significant influence on its biological effects. Inhalation of crystalline silica causes silicosis, also called pneumoconiosis or ‘black lung’ disease. Silicosis refers to pathological changes in the lungs caused by prolonged inhalation of quartz dust particles. Inhalable quartz dust has been classified as carcinogenic by the International Agency for Research on Cancer (IARC) . The European Network on Silica (NEPSI) published a good practice guide for the safe handling of crystalline silica at the workplace .
In a comparative study, two groups of rats inhaled crystalline quartz particles or amorphous silica nanoparticles for three months. After this treatment Inflammatory reactions in the lungs were analysed. The crystalline form triggered significant inflammation that did not subside, whereas the amorphous silica induced a temporary inflammation only at high doses, which subsided after a short recovery time, and no further negative effects were observed . This behaviour of the two different structural forms of SiO2 is confirmed by further scientific work .
The amorphous silica was tested in two laboratory studies according to OECD guidelines. The rats inhaled the nanoparticles for short periods of time (5 and 28 days, respectively) at different doses and then they were examined for possible effects of SiO2 in the lungs. However, there were no negative effects observed in these experiments [5, 6]. During the same period, several experiments were also conducted with rats and similar nanoparticles, but with the method of instillation, which is very different from inhalation exposure, as it is less realistic and usually produces very high local concentrations in the lungs. In these studies, inflammatory reactions and oxidative stress were observed in the lungs of the experimental animals [7 - 9], but they occurred exclusively when the lungs were overloaded with particles, the so-called "overload effect". This effect always occurs when the cleaning processes of the lungs are overloaded .
The studies on lung exposure to silica demonstrate two things: on the one hand, this substance has hardly any effect in the amorphous form. On the other hand, however, overloading the lungs with dust particles must generally be avoided, since loading with high quantities or inhalation of high concentrations of particles over a prolonged period may well result in lung damage. However, this is not specific to silica, but applies to any form of dust particles that can be inhaled (see cross-sectional topic Granular Biopersistant Dusts). Under realistic conditions of everyday life, however, such a scenario hardly plays a role, since a situation cannot be found in which large quantities of dust are inhaled over weeks and months.
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- NEPSI (29.04.2016).Good Practice Guide on Workers Health Protection through the Good Handling and Use of Crystalline Silica and Products Containing it. .
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Uptake via the Skin – Dermal Uptake
Silicon dioxide is approved as a substance to be used in cosmetic products (e.g. skin care, toothpaste). Therefore, knowledge of possible absorption via the skin is an important factor in the safety assessment of this material.
Silicon dioxide in its amorphous form is found in many products, including skin care products or toothpaste. Since July 2013, substances deliberately added as nanoparticles in cosmetics must be labelled with the addition "(nano)" on the list of ingredients. The effects on the skin have been tested in numerous experiments, but only a few have investigated uptake into the body, as this is methodologically very difficult. Nevertheless, there are some very interesting results from recent studies. One study presented a direct comparison between a skin cell culture (HaCaT keratinocytes), a three-dimensional skin model ("EpiDerm®") and rabbit skin. It was shown that the isolated skin cells respond with a slight loss of viability only by treatment with very high concentrations of nanoparticles. However, the 3D model and rabbit skin did not show any loss of viability or skin irritation . Two years later, an extensive study was conducted to investigate different sized nanoparticles of amorphous silica and their penetration into human skin. Here it was observed, as studies with particles from other materials had already shown, that there was no penetration of the nanoparticles through healthy skin into the body  (see also Body Barriers "Nanoparticles and the Skin").
Very remarkable is a British study with the 3D model "EpiDerm®". This 3D model, along with other models, meanwhile replaces animal testing, as animal testing for all cosmetic products has no longer been permitted in Europe since 2013. These three-dimensional skin models are composed and behave exactly like human skin. They consist of the different layers that also make up our skin: in the deep layers the living, proliferating epidermal cells and towards the surface with dead keratinocytes that cover our skin with 10-15 layers of dead cells, also called stratum corneum. A comparative study by Swansea University showed that simple cell cultures of skin cells responded to high concentrations of SiO2 nanoparticles with an increase in DNA damage, while the more realistic 3D model showed no symptoms or biological effects . In this study, penetration of the nanoparticles into deeper cell layers could also be ruled out, so that the silicon dioxide did not come into contact with the living cells of the epidermal layer. Another study was even able to demonstrate a protective effect of the SiO2 nanoparticles . In animal experiments with mice, two skin sensitizers were used to induce symptoms of allergy. However, when the skin of the animals was simultaneously treated with silica, the allergic symptoms did not occur. This was true for the negatively charged and neutral nanoparticles. Those that carried positive charges on their surface did not show this protective effect.
Taken together, the results of the experiments on the treatment of skin and skin cells with silicon dioxide prove that these nanoparticles have no harmful effect on the skin and cannot enter the body through healthy skin.
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Uptake via the Gastro-Intestinal Tract – Ingestion
Amorphous silicon dioxide (SiO2) is considered non-toxic and is approved as a food additive (E551) and, because of its specific properties, is used in many food products as a filler or anti-caking agent. Due to the production conditions, this food additive may also contain a certain amount of nanoscale SiO2 particles. However, the majority of the produced SiO2 is needed for completely different applications, such as paints and varnishes, scratch-resistant surfaces, and many other everyday products.
In vitro studies with gastric or intestinal cells show that only very high concentrations of silica nanoparticles damage cells in culture [1, 2]. This is confirmed by another study in which different cell types from the gastrointestinal tract were treated with different concentrations of food-grade SiO2 nanoparticles. The cells did not show any toxic reactions at realistic concentrations, but only responded to very high doses of nano-silica with inhibited cell growth .
Another study also demonstrated a response of immune cells of the intestinal mucosa to relatively high concentrations of food-grade SiO2 nanoparticles. There was an uptake of the nanoparticles into the cells as well as an activation of intracellular signaling pathways . Furthermore, silica nanoparticles were able to stimulate the growth of intestinal cells in cell culture experiments . However, a true toxic effect was not observed here either.
Recent in vivo studies demonstrate that dietary SiO2 nanoparticles do not cause adverse effects in the gastrointestinal tract of rats. In these studies, 1.5 g/kg body weight per day was given for up to 90 days without any adverse effects on the test animals [6-9]. Although none of the studies listed here were conducted with food-approved silica, even these mostly surface-active variants were not harmful to the gastrointestinal tract. In addition, silicon dioxide is mostly excreted undigested due to its poor solubility .
Silicon dioxide has no negative effect in the gastrointestinal tract either as micrometer or nanometer sized particles. In most cases, variants are tested that are not approved for use in food at all, and yet even these modifications of SiO2 are not toxic.
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Uptake via medical application (iatrogenic)
Silicon dioxide is a pharmaceutical excipient and is used in pills, capsules, gels, ointments, and other applications. Cosmetics and personal care products also contain SiO2 to protect the skin or improve creams. Dietary supplements containing SiO2 are offered in pharmacies and drugstores to support hair and nail growth.
For silicon dioxide, an uptake in humans cannot be excluded because of the multitude of applications, also close to the body, or is even desired (food supplements, drugs). Since the beginning of the industrial use of silicon dioxide (since approx. 70 years), no negative effect has been observed for humans, neither for the microscale nor for the nanoscale particles.