Silicic acid, aluminum magnesium salt

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
After oral uptake most of the ingested sodium silicoaluminate is excreted via faeces. The minor part is hydrolysed in the gastrointestinal tract, absorbed and then rapidly excreted in the urine. Even after administration of up to 1000 mg/kg sodium silicoaluminate to rats, only about 1% of the dose was absorbed (Benke and Osborne 1979). After probable decomposition of sodium silicoaluminate in the gastrointestinal tract, the aluminium component was only poorly absorbed in dogs (Cefali et al. 1995).
The slightly soluble particles of silicic acid aluminium magnesium salt are small enough to reach the alveoli (see 1.3). In subchronic inhalation studies with synthetic amorphous silica having comparable or even smaller particle size, silica particles deposited in the lung causing exclusively local inflammatory effects. After a recovery period, none or only small amounts of silica could be recovered from the animals suggesting reversibility (Reuzel et al. 1991 and Johnston et al. 2000).
Sodium and magnesium are essential elements of the mammalian body. Salts of both metal ions are natural constituents of the regular human diet and are commonly used in low concentrations in pharmaceutical products (oral and inhalative route). No other than the physiological effects are expected to occur from the ingestion or inhalation of these ions.
Referring to the toxicokinetic properties of structurally related compounds, no risk potential is expected for MAS.

Additional information

See basic toxicokinetics.

Discussion on bioaccumulation potential result:

Studies in animals

Cefali et al. (1995) compared the oral bioavailability of silicium and aluminum from sodium silicoaluminate, Zeolite A, magnesium trisilicate and aluminum hydroxide in dogs. The test animals received each test compound as a single oral dose (capsule) separated by one week. The administration of 16 mg/kg sodium silicoaluminate lead to elevated silicon AUC (area under the curve) and C_maxvalues compared to controls. Mean plasma silicon AUC values were 7.7 ± 1.6 and 6.1 ± 1.9 mg*h/L, mean plasma silicon C_maxvalue were 0.67 ± 0.27  and 0.44 ± 0.17 mg/L for sodium silicoaluminate and the internal control aluminum hydroxide, respectively. However, the differences were not significant. There was also no statistically significant absorption of aluminum from the sodium aluminosilcate treatment compared to the control treatment with magnesium trisilicate.

The rate and extent of urinary excretion of silicon was determined in rats after a single oral administration of sodium silicoaluminate, Zeolite A, sodium silicate and magnesium trisilicate (Benke and Osborn 1979). Urinary silicon excretion increased rapidly after dosing and peak excretion rates occurred within 24 h in all test groups. The urinary excretion half-life for ingested sodium silicoaluminate was calculated to be 38 hours. The percentage of silicon that appeared in urine varied independently of the applied dose indicating that limiting factors are rather the production of soluble (absorbable) silicon in the gastrointestinal tract and the rate of gastro-intestinal absorption. No significant increases in aluminium levels were detected in the urine of sodium alumionsilicate treated rats compared to controls. Daily urinary aluminium excretion averaged 17.7 ± 3.2 µg for control and 15.1 ± 4.3 µg for sodium silicoaluminate treated rats.

 

Studies in humans

In 12 human volunteers, no significant increased renal excretion of SiO₂was found following single oral ingestion of 2500 mg synthetic amorphous silica (Aerosil or FK 700). For each test item, 5 males and 1 female (aged 22-28) received 2 x 1.25 g of the test compound each suspended in 250 mL apple juice each at day 4 (morning and midday) of an experimental period of 7 days. The urine was collected daily and analysed for the monomer SiO₂content. After ingestion of Aerosil at day 4, in 3 of 6 subjects, the SiO₂content was increased in urine (20-38 mg SiO₂) compared to day 3. For the other 3 subjects, the SiO₂excretion was decreased or unchanged.After ingestion of FK700 at day 4, the SiO₂excretion was increased in 5 of 6 subjects in urine (7-23 mg SiO₂) compared to day 3. One of 6 subjects showed a decreased SiO₂excretion (26 mg).Overall, increases in excretion were not unequivocally detectable. The small apparent increases were in marked contrast to the high dose of 2500 mg SiO₂applied.