Silicic acid, aluminum magnesium sodium salt

Endpoint summary

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.