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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given, scientifically acceptable

Data source

Reference
Reference Type:
publication
Title:
Urinary silicon excretion by rats following oral administration of silicon compounds
Author:
Benke GM and Osborn TW
Year:
1979
Bibliographic source:
Fd. Cosmet. Toxicol. 17, 123-127

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
The rate and extent of urinary excretion of silicon was determined in rats after oral administration of magnesium trisilicate, food-grade sodium aluminiumsilicate, sodium silicate or Zeolite type A.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Arogen 2000 (Zeolite A, manufactured by Huber Corporation)
- Chemical name: Zeolite, cuboidal, crystalline, synthetic, non-fibrous
- Framework: cuboidal
- Related CAS number: 1318-02-1
- Empirical formula: Na12(AlO2)12(SiO2)12 x 27H2O
- Analytical purity: no data
- Composition of test material, percentage of components: 14.7 % silicon, 16.4% aluminium and minor amounts of hydroxysodalite (
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
suspended in distilled water
Duration and frequency of treatment / exposure:
single doses
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 40, 200, and 1000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
yes, concurrent vehicle

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Silicon excretion was rapid during the first 24 hours. The test material which gave the greatest increase in silicon excretion varied depending on the dose level:
40 mg/kg: SS >= MgTS >= ZA (ca. 200 µg*) >>SAS
200 mg/kg: ZA (ca. 800 µg*) > MgTS >SAS (SS not tested)
1000 mg/kg: ZA (ca. 1400 µg*) > SS > MgTS >SAS

This pattern changed substantially for 24-48 hours collection period:
40 mg/kg: MgTS > SS >SAS = ZA (ca. control values)
200 mg/kg: SAS = ZA (ca. 100 µg*) > MgTS (SS not tested)
1000 mg/kg: SS > SAS > MgTS > ZA (ca. 100 µg*)
*excreted in urine/24 h

Percentage of the silicon dose recovered in urine (results only for zeolite A presented):
40 mg/kg: 12.1%
200 mg/kg: 11.4%
1000 mg/kg: 3.0%

The urinary excretion half-lives were:
ZA: 6-8 h
SS: 24 h
SAS: 38 h
MgTS: 16-20 h

The authors concluded that due to the fact that an increase in urinary excretion of all 4 substances was not directly in proportion to the increase in dose, it is possibly assigned to the saturation of some processes, related either to the absorption or to the excretion of silicon.

Particulate and total silicon in rat urine after the administration of zeolite A:

Silicon (µl/mL urine)
mg/kg total particulate
--------------
Control 6.5 ± 0.6 2.2 ± 1.1
40 26.2 ± 3.4 1.4 ± 0.3
200 64.7 ± 6.8 1.6 ± 1.3
1000 80.9 ± 13.5 2.2 ± 0.8

The total amount of silicon excreted increased with dose, whereas the particulate silicon was not increased above control levels. The authors concluded that toxic effects in the urinary tract would not result from single high doses of Zeolite A.

The daily urinary aluminium excretion did not significantly exceed the value of the control group (the detection limit of the analytical method would have permitted the detection of 0.01 to 0.2 % of the dose).
Daily urinary aluminium excretion averaged as follows:
Control: 17.7 ± 3.2 µg
ZA: 12.3 ± 1.1 µg
SAS: 15.1 ± 4.4 µg

Since it is known from literature, that aluminum is excreted in the urine, the authors concluded, that it is most likely that ZA and SAS breakdown occurred in the gastro-intestinal tract, and only the silicon portion was absorbed.
Toxic effects are not reported.

Applicant's summary and conclusion