Silanediol, 1-methyl-1-(1-methylethoxy)-, 1,1-diacetate

Endpoint summary

Additional information

Methyldiacetoxyisopropoxy silane was tested in four different GLP-Guideline studies for genetic toxicity.

Methyldiacetoxyisopropoxy silane was tested in an Ames test using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100 and the Escherichia coli strain WP2 uvrA . The substance was tested up to 5000 µg/plate with and without metabolic activation. No toxic effects occurred in all test groups, with and without S9 mix. Under the experimental conditions the test item did not induce mutations by base pair changes or frameshifts in the genome of the strains used (Wagner, 2001).

The test item methyldiacetoxyisopropoxy silane was assessed for its potential to induce structural chromosome aberrations in ovary cells of the Chinese hamster in vitro in two independent experiments. No toxic effects were observed after treatment with up to 5000 µg/mL of the test item. No statistically significant or biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. No increase in the frequencies of polyploid metaphases was found after treatment with methyldiacetoxyisopropoxy silane compared to the frequencies of the controls (Gudi, 2001).

The test item methyldiacetoxyisopropoxy silane was assessed in a GLP study according to OECD 476 for its potential to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y.

The assay was performed in duplicates. The experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The selection of the maximum concentrations of 5000 µg/mL without S9-mix and 4000 µg/mL with S9-mix were based on data from the pre-experiment. The test item was investigated at the following concentrations:

+S9: 1500, 2000, 2500, 3000 and 4000 µg/mL

-S9: 2000, 2500, 3000, 4000 and 5000 µg/mL

Relevant toxic effects indicated by a relative total growth of less than 50 % of relative total growth were observed in at 4000 µg/mL in the presence of metabolic activation. No biologically relevant increase of mutants was found after treatment with the test item (with and without metabolic activation). No dose-response relationship was observed. Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced mutant colonies, indicating that the tests were sensitive and valid. In conclusion it can be stated that during the mutagenicity test described and under the experimental conditions reported the test item did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation (San, 2001).

To investigate the potential of methyldiacetoxyisopropoxy silane to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse, a GLP study according to OECD 474 was performed.

Methyldiacetoxyisopropoxy silanewas prepared in either distilled water (first experiment) or corn oil (second experiment). The test substance was administered intraperitoneal at a volume of 20 mL/kg bw by a single injection.

Five animals per test group were evaluated for the occurrence of micronuclei. At least 2000 polychromatic erythrocytes (PCEs) per animal were scored for micronuclei.

Based on preliminary tests the following dose levels of the test item were investigated:

1. Experiment: 50, 100 and 200 mg/kg bw

2. Experiment: 87.5, 175 and 300 mg/kg bw.

In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item with any dose level used.

Thus, methyldiacetoxyisopropoxy silane did not induce the micronucleus frequency under the given test conditions (Gudi, 2001).

Short description of key information:
Genetic toxicity in-vitro in-vivo: negative
Genetic toxicity in-vivo: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to DSD (67/548/EEC) and CLP (1272/2008/EC) methyldiacetoxyisopropoxy silane does not meet the criteria to be classified regarding this endpoint.