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Additional information

In vitro gene mutation study in mammalian cells (mouse lymphoma assay):

One main experiment was performed. In this main experiment, L5178Y TK+/- 3.7.2c mouse lymphoma cells (heterozygous at the thymidine kinase locus) were

treated with the test material at eight dose levels, in duplicate, together with vehicle (distilled water) and positive controls. The exposure groups used were as follows: 4-hour exposures both with and without metabolic activation, and 24–hour exposure without metabolic activation. The dose range of test material was selected following the results of a preliminary toxicity test and was 39.06 to 2500 μg/ml for all three of the exposure groups.

The maximum dose level used was limited by formulation difficulties to the maximum achievable dose level of 2500 μg/ml, however, it should be noted that there was also evidence of marked test material-induced toxicity. A precipitate was observed at and above 156.25 μg/ml in all three of the exposure groups at the end of the exposure period in the mutagenicity test. The vehicle (solvent) controls had acceptable mutant frequency values that were within the normal range for the L5178Y cell line at the TK +/locus. The positive control materials induced marked increases in the mutant frequency indicating the satisfactory performance of the test and of the activity of the metabolising system. The test material did not induce any statistically significant or dose-related (linear-trend)

increases in the mutant frequency at any dose level, either with or without metabolic activation, in any of the three exposure groups.

Conclusion. The test material was considered to be non-mutagenic to L5178Y cells under the conditions of the test.

In vitro cytogenicity study in mammalian cells (chromosome aberration test):

Duplicate cultures of human lymphocytes, treated with the test material, were evaluated for chromosome aberrations at four dose levels, together with vehicle and positive controls. Three treatment conditions were used for the study, i.e. 4 hours exposure in the absence of metabolic activation (S9) with a 20-hour expression period, 4 hours in the presence of an induced rat liver homogenate metabolising system (S9), at a 2% final concentration with cell harvest after a 20-hour expression period and a 24 hours continuous exposure in the absence of metabolic activation. All vehicle (solvent) controls had frequencies of cells with aberrations within

the range expected for normal human lymphocytes. All the positive control materials induced statistically significant increases in the

frequency of cells with aberrations indicating the satisfactory performance of the test and of the activity of the metabolising system.

The test material was only moderately toxic and did not induce any statistically significant increases in the frequency of cells with aberrations, in any of the exposure conditions, using a dose range that was limited by test material precipitation.

Conclusion. The test material was considered to be non-clastogenic to human lymphocytes in vitro.

In vitro gene mutation study in bacteria (Ames test):

Salmonella typhimuriumstrains TA1535, TA1537, TA98, TA100 were treated with suspensions of the test material using both the Ames plate incorporation method at five dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolising system (10% liver S9 in standard co-factors). The dose range was determined in a preliminary toxicity assay and was 50 to 5000 µg/plate in the first experiment. The experiment was repeated on a separate day (pre-incubation method) using the same dose range as Experiment 1, fresh cultures of the bacterial strains and fresh test material formulations. No toxicologically significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation or exposure method. The test material was considered to be non-mutagenic under the conditions of the test.


Short description of key information:
Three in vitro studies for genetic toxicity have been performed namely;
1. Mouse lymphoma assay for mutagenicity (OECD TG 476), 2. Chromasome aberation test for cytogenicity (OECD TG 473) and 3. AMES test for bacterial muatgenicity (OECD TG 471) .
All three tests recorded a negative result for genetic toxicity

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Silicic acid, lithium magnesium sodium salt was negative in all three genotoxicity assays and therefore does not warrant a classification in accordance to CLP or DSD.