Zeolite, cuboidal, crystalline, synthetic, non-fibrous

Basic toxicokinetics

Administrative data

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Urinary silicon excretion by rats following oral administration of silicon compounds.

Author:

Benke, G.M. and Osborn, T.W.

Year:

1979

Bibliographic source:

Food Cosmet. Toxicol. 27:123-127

Materials and methods

Objective of study:

excretion

Principles of method if other than guideline:

The rate of Zeolite Type A excretion was obtained from data on urinary excretion in rats after single oral administration.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Zeolite, cuboidal, crystalline, synthetic, non-fibrous

EC Number:

930-915-9

Cas Number:

1318-02-1

Molecular formula:

M2/nO • Al2O3 • ySiO2 • wH2O (n is the valency of the cation M, predominantly Na, y can range from 0.64 to 8.8, and w is the number of water molecules (general formula) Na: 1.34 - 24.02%, Al: 2.20 - 39.51%, Si: 15.52 - 68.64% (general composition); additionally, depending on the water quality: Ca, Mg and K might be present below 6%

IUPAC Name:

Zeolite, cuboidal, crystalline, synthetic, non-fibrous

Test material form:

solid: particulate/powder

Remarks:

no surface treatment

Specific details on test material used for the study:

- Name of test material (as cited in study report): Zeolite Type A (sodium aluminosilicate)(Huber Corporation)
- Analytical purity: no data
- Analyses showed that it contained 14.7 % silicon and 16.4% aluminium.

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Sprague-Dawley Cox

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 240-260 g
- Diet (e.g. ad libitum): Purina Rat Chow (1500-2000 ppm silicon)
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: 4-5 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

quartz-distilled (QD) water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: All suspensions were prepared in quartz-distilled water which contained < 0.5 ppm silicon and aluminium. Concentrations (w/w) of dosing materials were adjusted so that all groups received the same dosage volume (10 mL/kg). The acutal weights administered were calculated by difference.

Duration and frequency of treatment / exposure:

once

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

40 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw (total dose)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw (total dose)

No. of animals per sex per dose / concentration:

4

Control animals:

yes, concurrent vehicle

Details on study design:

For the determination of silicon in urine, the samples were dry-ashed, fluxed with Na2COJ, and then dissolved in hydrochloric acid. The concentrations of silicon in solution were measured by induction-coupled RF plasma optical emission spectrometry.

Details on dosing and sampling:

Rats were fasted for 17-18 hr, then dosed using a no. 10 French rubber feeding tube attached to a 3-ml plastic syringe. Concentrations (w/w) of dosing materials were adjusted so that all groups received the same dosage volume (10 ml/kg). The actual weights administered were calculated by difference. All suspensions were prepared in quartz-distilled (QD) water which contained <0.5 ppm silicon. Rats were dosed with 40, 200 or 1000 mg of test material/kg body weight. For each study a group of four or six control rats were given 10 ml QD water/kg body weight. Tail cups to collect faeces were used to prevent contamination of urine samples.

Statistics:

Group means were compared by Student’s t-test, except that when the values were not normally distributed a non-parametric test was used (Gibbons, 1971). The rates of excretion were fitted to zero-order and first-order kinetic equations (Barr, Goodnight, Sail, & Hellwig, 1976).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:

Zeolite Type A had an urinary excretion rate half-life time of 6-8 hr.

Particulare and total silicon in rat urine in the first 8 hours after the administration of Zeolite type A:
control group: 6.5 +/- 0.6 µg/ml urine (total); 2.2 +/- 1.1 µg/ml urine (particulate)
40 mg/kg group: 26.2 +/- 3.4 µg/ml urine (total); 1.4 +/- 0.3 µg/ml urine (particulate)
200 mg/kg group: 64.7 +/- 6.8 µg/ml urine (total); 1.6 +/- 1.3 µg/ml urine (particulate)
1000 mg/kg group: 80.9 +/- 13.5 µg/ml urine (total); 2.2 +/- 0.8 µg/ml urine (particulate)

It was of interest to find out whether particulate, or filterable, forms of silicon were produced during the time of maximum excretion in rats dosed with Zeolite Type A. While the total silicon concentration increased sharply with dose, the particulate silicon was not increased above control levels. The authors would, therefore, predict that toxic effects in the urinary tract would not result from single high doses of Zeolite type A.

Applicant's summary and conclusion

Conclusions:

Zeolite Type A had an urinary excretion rate half-life time of 6-8 hr.

Executive summary:

The rate and extent of urinary excretion of silicon was determined in rats after oral administration of magnesium trisilicate, food-grade sodium aluminosilicate, sodium silicate or Zeolite type A. Only the results on the latter are documented here.