Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
endocrine system modulation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Nov. 18, 2019 - Jan. 29, 2020, experimental phase: Nov. 28 - Dec. 4, 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
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:
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD 455
Version / remarks:
2016-09-08
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Silicic acid, aluminum magnesium sodium salt
EC Number:
234-919-5
EC Name:
Silicic acid, aluminum magnesium sodium salt
Cas Number:
12040-43-6
Molecular formula:
Na(0.017-1.739)Mg(0.008-0.823)Al(0.002-0.2473)SiO(2.018-3.837)
IUPAC Name:
aluminium(3+) magnesium(2+) sodium tris(oxosilanebis(olate))
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Name Silicic acid, magnesium aluminium sodium salt
CAS 12040-43-6
Batch no. 1901274010
Appearance white fluffy powder
Composition Sodium; Magnesium; Aluminium; Silica
Purity >95%
Molecular weight: 61.0204 -158.9696 g/moL
Homogeneity homogeneous

Test animals

Species:
other: bacteria
Strain:
other: Saccharomyces cerevisiae
Sex:
not specified
Details on test animals or test system and environmental conditions:
Species Saccharomyces cerevisiae
Mutations hERα and hAR receptor, expression plasmid carrying the reporter gene lacZ
The YES-YAS Assay Kit including Saccharomyces cerevisiae was obtained from Xenometrix AG, Gewerbestrasse 25, CH-4123 Allschwil, Switzerland.

Culture
Three days before the start of the experiment, the yeast cultures (YES and YAS) were prepared and incubated at 32 ± 1 °C for 2 days and 23 hours, until the cultures were clearly turbid. After incubation, the optical density was measured with a microplate reader. The cultures were diluted appropriately and then used for the experiment.

Administration / exposure

Route of administration:
other: incubated in humity container
Vehicle:
DMSO
Duration of treatment / exposure:
The assay plates were set into a humidity container and incubated for less than 48 hours at 32 ± 1 °C with agitation (100 rpm), because a colour change of the medium in the positive control wells indicated sufficient growth after 42 hours and 40 minutes.
Frequency of treatment:
once
Doses / concentrationsopen allclose all
Dose / conc.:
100 other: %
Dose / conc.:
31.6 other: %
Dose / conc.:
10 other: %
Control animals:
yes
Details on study design:
One valid experiment was performed.
Eight dilutions of an extract with Silicic acid, magnesium aluminium sodium salt in dimethyl sulfoxide (DMSO) and controls were exposed to the yeast cells in duplicate. The yeast cells were incubated with the test item and the controls for 2 days at 32±1 °C.

DMSO was used as solvent control.
As positive controls, the following substances were used:
17β-estradiol (E2) in the YES Agonist Assay, 4-hydroxytamoxifen (HT) in the YES Antagonist Assay, 5α-dihydrotestosterone (DHT) in the YAS Agonist Assay and flutamide (FL) in the YAS Antagonist Assay.

Results and discussion

Any other information on results incl. tables

The positive and solvent controls showed the expected results: In the solvent control no signs of endocrine activity were detected. The positive controls showed clear estrogenic and androgenic, agonistic and antagonistic activity in the YES and YAS assay.

After incubation with the test item extract dilutions and yeast cells, no cytotoxicity was observed.

 

The test item extract showed no positive result in any assay: The values for galactosidase activity and induction ratio of all test item dilutions lay in the same range as the values of the respective control. No dose-response correlation was visible.

Applicant's summary and conclusion

Conclusions:
Under the conditions of the test and the limited solubility as an inorganic UVCB, the extract of the test item Silicic acid, magnesium aluminium sodium salt is considered to have no estrogenic and androgenic agonistic and antagonistic activity in the YES YAS Assay.
As the test item was tested as an extract of an inorganic UVCB, it was not possible to state real concentrations. The concentration of the extract used was derived in the test. Therefore, the result has to be considered with reservations.
Executive summary:

This study was performed in order to evaluate the potential of estrogenic and androgenic agonistic and antagonistic activity of Silicic acid, magnesium aluminium sodium saltin the YES YAS Assay.