Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Studies in animals

Oral studies with aluminatesilicate that also included kinetic aspects of absorption, distribution and excretion have not been located.Therefore, read-across is made to respective findings with structure-analogous substances.

Cefali et al. (1995) compared the oral bioavailability of silicium and aluminium 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 led to elevated silicon AUC (area under the curve) and Cmaxvalues compared to controls. Mean plasma silicon AUC values were 7.7 ± 1.6 and 6.1 ± 1.9 mg*h/L, mean plasma silicon Cmaxvalue 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 aluminium from the sodium aluminosilicate 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 gastrointestinal absorption. No significant increases in aluminium levels were detected in the urine of sodium aluminosilicate 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.

 

Hence, it can be concluded that 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).

 

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) (Langendorf and Lang 1968). 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 SiO2 content 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.

 

Reference:

Benke, G.M. and Osborn, T.W. (1979): Urinary silicon excretion by rats following oral administration of silicon compounds. Food Cosmet. Toxicol., 27:123 -127.

Cefali, E.A. et al. (1996): Pharmacokinetic study of Zeolite A, Sodium Aluminosilicate, Magnesium Silicate and Aluminium Hydroxide in Dogs. Pharmaceutical Research, 12(2): 270 -274.

Langendorf and Lang (1968): Der Einfluss polymerer Kieselsaeuren auf die renale SiO2 Ausscheidung beim Menschen. Zeitschrift fuer Ernaehrungswissenschaft 8 (1-3): 27 -32