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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Silicic acid Aluminium Magnesium Sodium Salt had no mutagenic potential in the Bacterial Reverse Mutation. (Andres, 2015, OECD 471)

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and Guideline conform; B13.14 is a replicate of OECD 471.
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
7/1997
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Landesamt für Umweltschutz und Gewerbeaufsicht, Rheinland-Pfalz
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
Identification: Silicic acid Aluminium Magnesium Sodium Salt
Batch: code # 1107274003
Purity: > 99%
Appearance: White powder
CAS: 12040-43-6
Expiry Date: November 01, 2018
Storage Conditions: (provided by the Sponsor) At room temperature, moisture protected
Stability: Stable a room temperature
Target gene:
TA97a: hisD6610
TA98: hisD3052
TA100: hisG46
TA102: hisG428
TA1535: hisG46
Species / strain / cell type:
other: Salmonella typhimurium LT2 : TA97a, TA98, TA100, TA102 and TA1535
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
H2O, DMSO and positive Control
First experiment: 5000 / 1500 / 500 / 150 / 50 μg/plate
Second experiment: 5000 / 2500 / 1250 / 625 / 313 μg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Untreated negative controls:
yes
Remarks:
Water
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
without metabolic activation
Positive control substance:
sodium azide
other: 4-Nitro-1,2-phenylene diamine
Remarks:
Migrated to IUCLID6: and 4-Nitro-1,2-phenylene diamide (6 µg and 80 µg, respectively)
Untreated negative controls:
yes
Remarks:
Water
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
with metabolic activation
Positive control substance:
benzo(a)pyrene
other: 2-Amino-anthracene
Remarks:
Migrated to IUCLID6: and 2-Aminoanthracene (40 µg and 3 µg, respectively)
Details on test system and experimental conditions:
First experiment:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Incubation time:
- Incubation temperature: 37 °C

NUMBER OF REPLICATIONS: per strain and dose, four plates with and four plates without S9 mix were used.


Second experiment:
METHOD OF APPLICATION: preincubation

DURATION
- Incubation time: 20 min.
- Incubation temperature: 37 °C

NUMBER OF REPLICATIONS: per strain and dose, four plates with and four plates without S9 mix were used.
Evaluation criteria:
A test item is considered to have mutagenic potential, if a significant, reproducible increase of revertant colonies per plate (increase factor >= 2) in at least one strain can be observed.
Statistics:
A spreadsheet software was used to calculate mean values and standard deviations as well as the increase factor of revertant induction.
Key result
Species / strain:
S. typhimurium, other: TA 97a, 98, 100, 102 and 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

The test item did not show mutagenic effects in both experiments. The number of revertant colonies was not increased in comparison with the spontaneous revertants (solvent only).

Cytotoxicity of the test item was not detected. The bacterial background lawn was visible and the number of revertants was not significantly decreased.

As no complete dissolution was possible, undissolved particles were visible on the plates in both experiments in the two highest concentrations.

Therefore it can be stated, that under the test conditions, the test item Silicic acid Aluminium Magnesium Sodium Salt is not mutagenic in the Bacterial Reverse Mutation.

Test using Salmonella typhimurium, strains TA97a, TA98, TA100, TA102 and TA1535.

Conclusions:
Interpretation of results: negative

Silicic acid Aluminium Magnesium Sodium Salt has no mutagenic potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Based on the negative results of tested sodium silicoaluminate in an in vivo study, no mutagenic potential is expected from the exposure to silicic acid, aluminium magnesium sodium salt.

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
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
Justification for type of information:
Test material ist different from reference substance but comparable, see chapter 13, attachment 'Analogue Approach Justification'
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline available
Principles of method if other than guideline:
The host organism is inoculated by intraperitoneal injection with a common indicator microorganism/tester strain before treatment with the test substance. After "incubation" in the host organism, the tester strain is withdrawn from the ascites and tested for mutation on minimal agar plate., e.g. accroding to Ames.
GLP compliance:
not specified
Type of assay:
other: host mediated assy
Specific details on test material used for the study:
FDA-Compound 71-45, "sodium silicoaluminate",
synthetic silica
Lot no. SR-1621
Species:
mouse
Strain:
ICL-ICR
Sex:
male
Route of administration:
oral: gavage
Details on exposure:
Type: Salmonella typhimurium reverse mutation assay
Method: The test substance was administered orally to 10 host animals per dose. In the acute study the bacteria (Salmonella typhimurium TA 1530 and his G-46)were inocculated i.p. after the administration of the test substance. In the subacute study the bacteria were injected after the last administration of the test substance. Negative (0.85 % saline) and positive (100 mg/kg dimethylnitrosamine) controls were run in parallel. The animals were sacrificed three hours after administration and the bacteria were removed from the peritoneal cavity. The induction of reverse mutation was quantified on agar plates. 
Duration of treatment / exposure:
single administration ("acute") and repeated administration (5 times, "subacute")
Frequency of treatment:
1x and 5x (1x/d)
Dose / conc.:
4.25 mg/kg bw/day (nominal)
Remarks:
suspended in 0.85 % saline, administered 1x/d (Test I)
Dose / conc.:
42.5 mg/kg bw/day (nominal)
Remarks:
suspended in 0.85 % saline, administered 1x/d (Test I)
Dose / conc.:
425 mg/kg bw/day (nominal)
Remarks:
suspended in 0.85 % saline, administered 1x/d (Test I)
Dose / conc.:
5 000 mg/kg bw (total dose)
Remarks:
suspended in 0.85 % saline (Test II)
No. of animals per sex per dose:
10 (males only)
Control animals:
yes, concurrent vehicle
Positive control(s):
yes, treated with 100 mg/kg bw Dimethylnitrosamine (DMN)
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
not examined
Positive controls validity:
valid
Additional information on results:
There was a high increase in mutants following oral treatment with Dimethylnitrosamine (DMN), but no significant increases in mutation rates at any dose and dose regimen.
Conclusions:
There was a high increase in mutants following oral treatment with DMN, but no significant increases in mutation rates at any dose and dose regimen.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

In vitro data

Silicic acid Aluminium Magnesium Sodium Salt, synthetic amorphous silica and sodium silicoaluminate did not show mutagenic activity in in vitro systems in the presence and absence of an external metabolising system: These included bacterial Salmonella typhimurium strains (Andres 2015, Litton 1974 bacteria/yeast) and mammalian cell lines (Litton 1974 human lung cells (two times, with SAS and ASA), Geissel 2020).

 

In vivo data

A host mediated assay conducted with sodium silicoaluminate in mice did not show a significant increase in mutation rates at any dose and dose regimen. (Litton 1974).

Justification for classification or non-classification

No need for classification as the in vitro and in vivo studies consistently demonstrate negative results for

Silicic acid Aluminium Magnesium Sodium Salt and structurally related compounds.