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Additional information

An Ames test is available with disodium disilicate (delta-crystalline). For other genotoxicity tests in vitro and in vivo, read across to soluble silicates (sodium silicate and sodium metasilicate) was done due to the fact, that the substances are almost identical. Disodium disilicate (delta-crystalline) differs from the soluble silicates only in the crytal structure and the molar ratio of sodium and silicate. When dissolved in water so called waterglas is formed from all 3 components. In the human body (water based system) silicates are naturally occurring and concentration levels are well controlled. Thus read across is justified in this case.

Genetic toxicity in vitro

Ames test

The test substance disodium disilicate (delta-crystalline) was tested for mutagenicity in the TA 98, TA 100, TA 1535, TA 1537, TA 1538 strains of Salmonella typhimurium. The mutagenicity studies were conducted in absence and presence of a metabolizing system derived from rat liver homogenate. A dose range of 6 different doses from 4 µg/plate to 5000 µg/plate was applied. Control plates without the test substance/ mutagen showed that the number of spontaneous revertant colonies (his+ revertants) were similar to that described in the literature. All positive control compounds resulted in the expected increase in the number of revertant colonies. Toxicity results showed that the test compound proved to be not toxic to the bacterial strains and 5000 µg/plate of the test substance was chosen to be the highest applied concentration in the mutagenicity assay due to a precipitation limit. The test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains in the absence and in the presence of the metabolic activation system. Disodium disilicate (delta-crystalline) did not result in relevant increases in the number of revertant colonies. Therefore, it can be stated that disodium disilicate (delta-crystalline) is not mutagenic at the investigated dose levels in the examined bacterial test systems with or without exogenous metabolic activation.

Chromosome aberration test

In a mammalian cell cytogenetics assay (Chromosome aberration assay) V79 cell cultures were exposed to sodium silicate (36% active ingredient, 64% water) at concentrations of 19.5, 39.1, 78.1 & 156.3 µg active ingredient/ml with and without metabolic activation (Phenobarbital/ß-Naphthoflavone induced rat liver S9-mix).

Sodium silicate was tested up to cytotoxic or precipitating concentrations. Positive controls induced the appropriate response. There was no evidence of chromosome aberration induced over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline (In vitro mammalian cytogenetics, OECD 473) for in vitro cytogenetic mutagenicity data.

HPRT-test

The study was performed to investigate the potential of C-SAT 080094 to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster.

The assay was performed in three independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours. The experimental part without metabolic activation was terminated prematurely due to exceedingly severe cytotoxic effects even at low concentrations. This part of the first experiment was repeated in experiment IA using a lower concentration range. The data of the repeat experiment IA are included in the first experiment.

The second experiment was performed in the absence of metabolic activation with a treatment period of 24 hours and in the presence of metabolic activation with a treatment period of 4 hours.

The highest applied concentration in the pre-test on toxicity (7300 µg/mL) was based on the purity of the test item (36 % active ingredient). The dose range of the main experiments was limited by toxicity of the test item.

No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments.

Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.

Genetic toxicity in vivo

Sodium metasilicate was tested in a cytogenetic test for chromosome aberrations in bone marrow cells of male mice in a study similar to OECD TG 475 with the restriction that no information on the use of positive controls was available. Groups of 4 - 6 animals were administered single oral doses of sodium metasilicate at dose levels between 740 and 1340 mg/kg bw (in total, seven dose levels were used in this study). Animals were sacrificed 24 hours after the last administration of the test substance; 2 hours before sacrifice a metaphase arresting agent (colchicine; 4 mg/kg bw) was injected intraperitoneally. Slides from femur bone marrow cells were prepared according to standard methods, and 100 metaphases per animal were analyzed for chromosomal aberrations (including gaps, breaks, deletions, and exchanges). No indication of chromosomal aberrations was detected. In a range-finding study, no mortality occurred within 4 days after administration in animals up to 940 mg/kg bw. Mortality occurred at higher doses (Saiwai et al. 1980).


Short description of key information:
Disodium disilicate (delta-crystalline) was shown to be negative in an Ames test. For higher tier genotoxicity testing read across to soluble silicates was done, as no further studies are available for disodium disilicate (delta-crystalline). It could be shown, that sodium silicate is negative in an in vitro chromosome aberration and in vitro HPRT test both in V79 cells. In addition it could be shown that sodium metasilicate does not induce chromosome aberrations in an in vivo mouse bone marrow chromosome aberrations test. Thus, it is concluded that soluble silicates and consequently disodium disilicate (delta-crystalline) does not have a genotoxic potential.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of genotoxicity testing, disodium disilicate (delta-crystalline) has not to be classified in regard of genotoxicity according to Regulation 1272/2008/EC (CLP) and Directive 67/548/EC (DSD).

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