Disodium metasilicate

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented publication giving sufficient detail for evaluation.

Objective of study:

excretion

Principles of method if other than guideline:

The excretion of silica (SiO2) in urine after oral or inhalative administration of silicate to cats was studied.

GLP compliance:

no

Radiolabelling:

no

Species:

cat

Sex:

not specified

Route of administration:

other: oral and inhalation

Vehicle:

unchanged (no vehicle)

Details on excretion:

Administration of silicic acid freshly precipitated from a sodium metasilicate solution (corresponding to 5 g SiO2) lead to markedly increased silica excretion in the urine as compared to the control. The urinary silica excretion returned to the normal level of excretion  within 3 days. A fog of 2% sodium metasilicate solution carefully neutralized with hydrochloric acid to avoid precipitation of silicic acid was administered to cats by means of  an atomizer blowing into a rubber mask attached to the cat's nostrils. A  marked increase in the silica (SiO2) of the urine was observed which persisted for several days after the experiment was concluded. The dust of air-dried and finely ground amorphous silica obtained from a sodium metasilicate solution by acid precipitation was adminstered for 6 hours  to the nostrils of cats using a rubber mask. A big transitory increase in urinary silica excretion was observed.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented publication giving sufficient detail for evaluation.

Objective of study:

excretion

Principles of method if other than guideline:

Guinea pigs fed with diet containing Na-metasilicate. Colorimetric determination of silica excreted via urine and feces.

GLP compliance:

no

Radiolabelling:

no

Species:

guinea pig

Details on excretion:

In guinea pigs the total silica eliminated (urinary and fecal SiO2) was measured after oral administration of (1) a single dose of sodium metasilicate (pentahydrate) equivalent to 80 mg SiO2, and (2) four doses of sodium metasilicate (pentahydrate) equivalent to 80 mg SiO2 at 48-hr intervals. Within 8 days, 60% of the silica administered as a single dose and 96% of the silica administered as multiple doses was excreted. The urinary excretion was apparently limited by restricted absorption from the gastrointestinal tract.

Additional information

There were only limited experimental studies available in which the toxicokinetic properties of disodium metasilicate were investigated. Therefore, whenever possible, toxicokinetic behaviour was assessed taking into account the available information on physicochemical and toxicological characteristics of disodium metasilicate according to “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2009)”.

Disodium metasilicate is comprised of infinite chains of Na2SiO3 units of variable length. It is a crystalline, anhydrous powder and is highly soluble in water (210 g/L at 20 °C). Since the aqueous solution is characterised by dynamic polymerisation/hydrolysis equilibrium of monomeric SiO2 (aq.), oligomeric silicate ions and polysilicate ions, determination of quantitative water solubility is strongly pH-dependent. At 1175 °C, disodium metasilicate possesses a vapour pressure of 1.03 Pa. As a consequence the vapour pressure at ambient temperatures is negligibly low and thus not relevant. The partition coefficient n-octanol/water is also not relevant, as alkali silicates are ionisable inorganic compounds which are not soluble in alcohol.

Primarily disodium metasilicate is characterised by its molar ratio (SiO2:Na2O) of 1.0 and due to the equimolar ratio, it has a regular crystalline structure.

Disodium metasilicate is produced either by direct fusion of precisely measured portions of pure silica sand (SiO2) and soda ash (Na2CO3) to yield a molar ratio of 1.0 at temperatures above 1000 °C or it is produced by hydrothermally dissolving a reactive silica source (mainly silica sand) in sodium hydroxide solution. Crystalline sodium silicate powders of a specific composition but containing various amounts of water of crystallisation can be produced by blending sodium silicate solutions and additional caustic soda (NaOH) to achieve a mother liquor with a molar ratio of 1.0, from which the final product is crystallised to yield disodium metasilicate pentahydrate or disodium metasilicate nonahydrate.

 

Absorption and distribution

Acute oral toxicity studies have been conducted in rats and mice using various test concentrations (10-99%) of disodium metasilicate. However, in the majority of theses studies only limited details were reported. In a study referred to by Sawai et al. (1980) and Ito et al. (1986), male and female rats were administered disodium metasilicate at the dose levels of 538 – 2600 mg/kg bw. Clinical symptoms observed in a dose-dependent manner consisted of lethargy, tonic convulsions and respiratory paralysis. Histopathology revealed bleeding in the gastrointestinal tract in the animals that died. Surviving animals had no significant changes. The LD50 value was determined to be 1152-1349 mg/kg bw for both sexes. In another study referred to by Saiwai et al. (1980) and Ito et al. (1986), mice were administered the test substance in dose levels of 500 – 1920.8 mg/kg bw. In a dose-dependent manner, animals showed lethargy, ataxia, tonic cramps, and respiratory paralysis. At necropsy, bleeding of the stomach and the duodenum, clear liver lobules and faded colour of the liver was found. The LD50 was calculated to be 770- 820 mg/kg bw.

The findings of the available acute oral toxicity studies evidenced that the main cause of acute toxicity was most probably local irritation at the site of contact due to the highly alkaline test substance.With regard to the dose administered and the effects observed, systemic bioavailability of the test substance is considered to play only a minor role.

This is confirmed by oral repeated dose toxicity studies performed in rats, mice and turkeys which showed no treatment-related effects on gross pathology and histopathology (Ito et al., 1975; Saiwai et al., 1980; Kayongo-Male and Jia, 1999). The only treatment-related effects observed in rats after administration of disodium metasilicate pentahydrate for 90 days were reduction of blood plasma Ca and Mg and liver Zn concentrations at 1259 mg/kg bw/day. In female mice, a reduced pituitary gland weight was observed at 716-892 mg/kg bw/day (disodium metasilicate) after treatment for 90 days and in turkeys, blood plasma phosphate was increased and Cu decreased at 2039 mg/kg diet (disodium metasilicate pentahydrate) after 28 days. From the available repeated dose toxicity studies a NOAEL of 227 - 237 mg/kg bw/day and of 260-284 mg/kg bw/day was derived for rats and mice, respectively. Both effect levels correspond to the highest dose tested.

No data on acute inhalation toxicity are available on disodium metasilicate. As a consequence of the very low vapour pressure of disodium metasilicate, inhalation is not considered to be a significant route of exposure. Furthermore, commercial disodium metasilicate contains only particles of > 200 µm in granular products, or > 50 µm in powders (Minihan and Lovell 2008; Rhodia 2003 and 2001; Cognis 2003) and therefore isessentially non respirable. Due to the hygroscopic properties and the ready solubility in water, the majority of particles, if inhaled, will be retained and dissolved by mucus in the upper respiratory tract. Thus, effects would be restricted to local corrosive/irritant effects, due to the intrinsic alkalinity of disodium metasilicate. Also based on the hygroscopic properties, anhydrous disodium metasilicate tends to aggregate in the presence of moisture. A case report demonstrated that after ingestion of 500 mL of an egg-preserving solution containing sodium silicate in suicidal intention a 68 year old woman died within 1 h by suffocation (Schleyer and Blumberg, 1982; Sigrist and Flury, 1985). Aspiration of the vomited silicate solution caused obstruction of the lungs by precipitation of amorphous silica. The transformation of sodium silicate from liquid to solid occurred in the lungs by means of the carbonic acid of expiration air.

No data on acute dermal toxicity are available on disodium metasilicate. However, with respect to the intrinsic alkalinity of disodium metasilicate it is predicted that the primary effect after dermal exposure will be local skin irritation to corrosion at the site of contact. Based on infinite chains of Na2SiO3 units of variable length and as disodium metasilicate is an inorganic compound, QSAR based dermal permeability taking into account molecular weight, log Kow and water solubility is not feasible.

However, it can be assumed that dermal bioavailability is rather limited due to the high water solubility, the very low lipophilicity and the molecule size of disodium metasilicate.

 

Metabolism

From the chemical structure of disodium metasilicate, it can be deduced that disodium metasilicate is not metabolised in-vivo. By calculating potential metabolites via OECD QSAR toolbox v.2.3 (2012), this assumption is confirmed: Metabolites were generated neither by the liver metabolism simulator nor by the skin metabolism simulator nor by the microbial metabolism simulator. Based on this information, it is considered to be very unlikely that disodium metasilicate will be metabolised by cytochrome P450 enzymes in-vivo. Repeated dose toxicity studies via the oral route performed in rats, mice and turkeys also support the hypothesis that there are no reactive metabolites of disodium metasilicate in-vivo.The cause of toxicity in these studies was mainly governed by the intrinsic alkalinity of the test substances. In addition, studies with disodium metasilicate in mice did not induce chromosome aberrations in the bone marrow and did not alter cell proliferation in the auricular lymph nodes using the local lymph node assay (Ito et al, 1986; Saiwai et al., 1980; Karrow et al., 2002). Moreover, studies on genetic toxicity in-vitro were all negative with disodium metasilicate nonahydrate (Ames test) or with sodium silicate (gene mutation in mammalian cells in-vitro, chromosome aberration in-vitro), indicating that there is also no evidence of reactivity under the in-vitro test conditions (BASF SE 2012; Schulz, 2006; Wollny 2009).

 

Excretion

Since disodium metasilicate is a polar substance and highly water soluble, its elimination mainly occurs by the kidneys.In the excretion study of Sauer et al. (1959), sodium metasilicate pentahydrate was administered to guinea pigs by the oral route.Urinary silicon levels were measured after a single dose or after repeated doses (4 doses) of sodium metasilicate pentahydrate (equivalent to 80 mg SiO2). The excretion rates were neither precisely determined nor were detailed dose-response data obtained. Within 8 days, 60% of the silica administered as a single dose and 96% of the silica administered as repeated doses was excreted. The urinary excretion was apparently limited by restricted absorption from the gastrointestinal tract.

Therefore, the excretion rate was independent of the doses applied indicating that the limiting factor is the rate of production of soluble or absorbable silicon in the gastrointestinal tract.

Markedly increased and rapid urinary excretion of silica was also observed when various “soluble silicates” were administered to rats (oral, Benke and Osborn, 1979), dogs (oral and intravenous, King et al., 1933) and cats (oral, intraperitoneal and inhalative, King and McGeorge, 1938).Benke and Osborne (1979) determined urinary excretion levels of silicon after single oral administration of

sodium silicate (analytical amount of silicon: 25.9%). The dose levels were 40 and 1000 mg/kg bw. Urine was collected in periods of 0 – 24, 24 – 48, 48 – 72 and 72 – 96 hours after dosing.The rats excreted urinary silicon in excess of background levels. The urinary silicon excretion increased rapidly after dosing and the majority of silicon was excreted during the first 24 hours. For sodium silicate, a half life of 24 hours was determined with a first-order excretion kinetic. The amount of silicon excreted in urine increased with the dose level, but when expressed as percentage of dose, the urinary silicon excretion decreased with increasing dose (18.9% of silicon dose recovered in urine at the low dose and 2.8% at the high dose). The fact that the increase in urinary excretion was not in direct proportion to the increase in dose may have been due to the saturation of some processes, related either to the absorption or to the excretion of silicon. Similar findings were reported by King et al. (1933), who administered silicic acid to dogs and found that increasing the dose caused a smaller fraction of the silicon to be excreted in urine. Benke and Osborne (1979) proposed that an acid mediated hydrolysis in the gastrointestinal tract is responsible for forming soluble or absorbable forms of silicon and that, therefore, lower silicon doses are not excreted more rapidly.

Silicon is an essential ultratrace element participating in the normal metabolism of the mammalian body. It is required in bone, cartilage and connective tissue formation as well as participating in other important metabolic processes. Also, sodium is an essential element of the mammalian body. The salt of the metal ion is a natural constituent of the regular human diet.

Taking into account all available data, the biological properties of disodium metasilicate are mainly governed by its intrinsic alkalinity. Disodium metasilicate was shown to possess a low systemic toxicity and is therefore expected to have only a low potential to accumulate in biological systems.

 

Literature (not cited in IUCLID):

Benke, GM. and Osborn, TW. (1979) Urinary Silicon Excretion By Rats Following Oral Administration Of Silicon Compounds. Fd. Cosmet. Toxicol. 17, 123-127

King, EJ. et al. (1933) The biochemistry of silicic acid III. The excretion of administered silica. Biochem. J. 27, 1007-1014