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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 (OECD TG 471 (1997)) (Donath, C. (2012))
Cytogenicity in mammalian cells: positive with metabolic activation (OECD 473 (1997)) (Hofman-Huether, H., 2013); registration substance
Mutagenicity in mammalian cells: Testing is not required as a positive result was obtained in the cytogenicity study


In vivo:
An in vivo micronucleus assay is proposed to follow up the positive result in the in vitro cytogenicity study.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Additional information

Amino functional alkoxysilanes have been tested in a study conducted according to OECD TG 471 and in compliance with GLP (Donath, C., 2012). No test-substance related increase in the number of revertants was observed with or without metabolic activation in either the initial plate incorporation assay or the repeat experiment using the pre-incubation method in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 up to limit concentrations. Toxicity was observed in one strain in the absence of metabolic activation at the highest concentration tested. Appropriate positive and solvent controls were included and gave expected results, apart from the solvent and positive controls for TA 1535 with metabolic activation in experiment 1, where the mean values for both controls were just below the range of historical controls. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Evidence of potential for clastogenicity was obtained when amino functional alkoxysilanes was tested for cytogenicity to mammalian cells in Chinese hamster V79 cells according to OECD 473 and under GLP (Hofman-Huether, H., 2013). Appropriate positive controls were included and gave expected results. The experiment was conducted with and without activation, and cells were exposed for four hours. Single cultures were used, and the experiment was not repeated because a positive result was reported. There was an increase in the number of cells with aberrations above solvent control levels at the highest concentration in the absence of metabolic activation, and at all concentrations evaluated that had been tested in the presence of metabolic activation. The evaluation of the slides from two of the doses (with metabolic activation) showed different results, so more than 200 metaphases were scored at these concentrations. The author of the report considered that this may possibly be an effect of the solubility of the test item. It is noted by the reviewer that extra cells were counted for the solvent control, presumably because of the variability between slides (0% and 4% aberrant cells excluding gaps), which suggests that experimental technique might have contributed to the variability. In addition it is noted by the reviewer that there was not a clear dose response with metabolic activation. It is concluded by the author of the report that the test substance was positive for the induction of structural chromosome aberrations (was clastogenic) under the conditions of the test.

Testing for mutagenicity to mammalian cells is not required as a positive result was obtained in the in vitro cytogenicity study.

An in vivo micronucleus study is proposed to investigate the potential for clastogenicity indicated by the results of the in vitro cytogenicity study.

Justification for classification or non-classification

Results from an in vitro mammalian cell cytogenicity assay indicated potential for clastogenicity, so in vivo testing is proposed.