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Administrative data

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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
excretion
Principles of method if other than guideline:
The rate of Sodium aluminosilicate excretion was obtained from data on urinary excretion in rats after single oral administration.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): sodium aluminosilicate, tradename: Zeolex (Huber Corporation)
- Analytical purity: no data
- Other: Huber Corporation specified that this compound met all the purity and quality specifications of the Food Chemicals Codex; the analyses showed that it contained 30 % silicon and 5.4% aluminium.

Remark: All of the ZEOLEX® products were amorphous sodium aluminum silicates (sometimes called sodium silico aluminates).
Radiolabelling:
no
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

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
Dose / conc.:
40 mg/kg bw (total dose)
Dose / conc.:
200 mg/kg bw (total dose)
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).
Details on excretion:
The percentage of silicon that appeared in urine varied independently of the dose. The urinary excretion half-life for ingested sodium aluminosilicate was calculated to be 38 h.
Conclusions:
The urinary excretion half-life for ingested sodium aluminosilicate was calculated to be 38 h.
Executive summary:

The rate and extent of urinary excretion of silicon were determined in rats after oral administration of magnesium trisilicate, food-grade sodium aluminosilicate, sodium silicate or Zeolite type A. Only the results on sodium aluminosilicate (Silicic acid, aluminum sodium salt (CAS 1344-00-9, NAS)) are documented here.

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan, 20 - Oct. 13, 2011; experimental phase: Jan. 26 - May 3, 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Objective of study:
absorption
distribution
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study is a further investigation of an OECD-guideline (407) repated dose oral one. It was performed for the chemical analysis of
silicon concentration (blood analysis) and the transmission of silicon particles in organ samples examined by electron microscopy.
GLP compliance:
no
Remarks:
The main study was performed under GLP conditions except for the chemical analysis of silicon concentration and the transmission electron microscopy of silicon particles in organ samples documented in this endpoint.
Specific details on test material used for the study:
SAS (Synthetic Amorphous Silica PR-A-02 ): NM-200
supplied by JRC, Ispra, on behalf of the sponsor, CEFIC, The European Chemical Industry Council
Radiolabelling:
no
Species:
rat
Strain:
Wistar
Details on species / strain selection:
purchased from: Charles River Deutschland, Sulzfeld, Germany
Sex:
male
Details on test animals or test system and environmental conditions:
Animals were housed in groups of 5 per cage in Makrolon Type IV cages in animal room T1.044 in the conventional area. Absorbent softwood was used as bedding material in the cages (Lignocel BK 8-15, ssniff GmbH, Soest, Germany). Drinking water from the Hannover city water supplier was offered fresh weekly, in Makrolon bottles (approximately 300 ml), ad libitum. Food was offered ad libitum fresh weekly. The diet used (ssniff R/M-H) was supplied by ssniff GmbH, Soest, Germany. The temperature in the animal room was set at 22 ± 2oC and the rel. humidity at 30 - 70%. The animal room lighting was a 12-hour light/dark cycle controlled by an automatic timing device.
Route of administration:
oral: gavage
Vehicle:
other:
Duration and frequency of treatment / exposure:
28 d, daily exposure
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose / concentration:
5
Control animals:
yes, concurrent vehicle
Details on study design:
s. below
Statistics:
Differences between groups were considered case by case as statistically significant for p<0.05. Data were analyzed using analysis of variance. If the group means differed significantly according to the analysis of variance, the means of the treatment groups were compared with the means of the control group, using DUNNETT's modification of the t-test. Kruskal-Wallis ANOVA and Mann-Whitney U-test were applied in the case of non-homogeneous data. The statistical evaluation of the histopathological findings was done with the two-tailed FISHER test using the PROVANTIS system. For comparisons of semiquantitative data, the Chi-square test was used.
Details on absorption:
Transmission electron microscopy (non-GLP) found electron dense structures composed of irregular homogenous to fine granular material in the cytoplasm of mesenteric lymph nodes cells, liver cells and kidney cells of all animals from the control and from the high dose group. The granular structures measured only few nanometer. However, these structures did not have the shape or appearance of amorphous material such as amorphous silica.
Details on distribution in tissues:
Determination of Silicon Ion Concentration
The results of the chemical analysis of silicon ion concentration are presented in Table 19. In summary, the ion concentrations in kidney, liver and blood were comparable in control animals (group 1) and high dose animals (group 4) and no treatment related changes were observed.

Determination of Silicon Particles
For electron microscopical investigation two samples per organ of the mesenteric lymph nodes, kidney as well as liver of all high dose group animals (group 4) were used. Vehicle treated animals served as controls (group 1).
To achieve better visibility of possible nanoparticles in comparison to the biological background composed of the organic structure, ultrathin sections have not been contrasted using uranyl acetate and lead citrate.

Mesenteric lymph node: Occasionally, cells of the mesenteric lymph node of all animals of the untreated group (group 1) and of the amorphous silica treated group (group 4) showed electron dense structures. Theses electron dense structures were found intracytoplasmatically in vacuoles and were characterized by irregular homogenous to fine granular material.
Liver: Occasionally, liver cells of all animals of the untreated group (group 1) and of all animals of the amorphous silica treated group (group 4) showed electron dense structures. Theses electron dense structures were found intracytoplasmatically in vacuoles and were characterized by irregular homogenous to fine granular material.
Kidney: Occasionally, kidney cells of all animals of the untreated group (group 1) and of all animals of the amorphous silica treated group (group 4) showed electron dense structures. Theses electron dense structures were found intracytoplasmatically in vacuoles and were characterized by irregular homogenous to fine granular material.
Conclusions:
Toxicological analysis of silica ion concentrations in blood, kidney and liver tissue did not reveal differences between the control and the dose group. This result is most likely due to the naturally occurring high background values of silica.
Executive summary:

This is a toxicokinetic examination of an oral 28-day study in rats. It showed, that silicon is naturally absorbed by the body, as shown by its presence in blood, kidneys and liver of treated as well as untreated animals.

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
experimental phase: Jun. 16, 2016 - Sep. 19, 2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Objective of study:
bioaccessibility (or bioavailability)
Qualifier:
no guideline followed
Principles of method if other than guideline:
Bioavailability was tested in three human cell lines: Test items were exposed at fixed concentration of 256 μg/mL for 1, 4 and 24 hours. TEM images were analyzed for the presence or absence of the test item inside the cells.
GLP compliance:
yes
Specific details on test material used for the study:
Sodasil P95
Radiolabelling:
no
Dose / conc.:
256 other: µg/ml
Bioaccessibility (or Bioavailability) testing results:
Regarding the bioavailability assessment of the test items to penetrate into the three cell lines, all of them were able to penetrate into the cells. The main presence was generally seen into the cytoplasm, some of them showing crystallographic aggregates, other totally dispersed and other that appeared to be in process of vacuolization. However, no clear data could be reached from the current data designs to discern whether nanosilicates are externalized or
remain into the cells for a long time.
Conclusions:
Sodasil P95 was able to be internalized into the cytoplasm of the three cell lines.
Executive summary:

The bioavailability of Sodasil P95 was tested in three cell lines (human hepatoma HepG2, human lung carcinoma A549 and human colorectal carcinoma CaCo-2). It was able to be internalized into the cytoplasm of the three cell lines.

Description of key information

The urinary excretion half-life of Silicic acid, aluminum sodium salt (CAS 1344-00-9, NAS) was calculated at 38 hours. 


 


In a study with the read-across substance, Silicon dioxide (SAS), silica ion concentrations in blood, kidney, and liver tissue did not reveal differences between the control and the dose group. This result was most likely due to the naturally occurring high background values of silica. In another study with another form of Silicon dioxide, also no bioaccumulation potential was assessed. 


 


Urinary excretion and elimination half-life time were also assessed with Silicon dioxides: Increases in excretion of SiO2 after oral ingestion were not unequivocally detectable. The small apparent increases on the average of less than 0.5 % of the total dose were in marked contrast to the high dose of 2500 mg SiO2 applied. The urinary elimination half-life time was less than 13 weeks.


 


In a study in the half-life isotope of aluminum the 5 h urinary 26Al excretion amounted to 0.1 +/- 0.02 % of the administered dose in the group Aluminium hydroxide. It was concluded that the fractional intestinal absorption of trace oral doses of aluminum hydroxide is at least 0.1% (compared with the previous estimate of 0.01% using large 27Al oral loads).


There is no study in dermal absorption.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information