Hydroxytrimethylsilane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535 or TA 1537, or E.coli WP2 uvrA (OECD TG 471) (Dow Corning Corporation, 1995).

Cytogenicity in mammalian cells: negative in Chinese hamster lung fibroblasts (Japanese guideline similar to OECD TG 473) (Hita laboratories, 1994).

Mutagenicity in mammalian cells: negative in L5178Y mouse lymphoma cells (similar to OECD TG 476, 1997) (Litton Bionetics, 1978).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Chromosome aberration assay in rat (ip administration): negative (similar to OECD 475) (Bioassay Systems Corporation, 1982).

Rodent dominant lethal assay in rat (oral gavage): negative (OECD 426 (1981), similar to OECD 478) (Dow Corning Corporation, 1983).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Trimethylsilanol has been tested for mutagenicity to bacteria, in a study which was conducted according to OECD TG 471, compliant with GLP (Dow Corning Corporation, 1995)). No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535 or TA 1537, or E. coli WP2 uvrA, in the initial or the repeat experiments using the plate incorporation method up to limit concentrations. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

The key study for mutagenicity to bacteria is supported by three older studies (Mitsubishi (undated); Litton Bionetics, 1978; Wacker, 1986). The results of all the studies are in agreement.

Trimethylsilanol has been tested for cytogenicity to mammalian cells in a study conducted according to a Japanese test guideline equivalent to OECD 473 and in compliance with GLP (Hita laboratories, 1994). No test-substance related increase in the number of cells with aberrations was observed when Chinese hamster lung fibroblasts were treated with 225, 450 and 900 μg/ml of test substance in the presence and absence of metabolic activation. No cytotoxicity was observed up to the limit concentration of 900 μg/ml (10mM). It was concluded that the test substance was negative for cytogenicity under the conditions of the test.

The key study for in vitro cytogenicity is supported by three older studies (Mitsubishi (undated); Litton Bionetics, 1978; Litton Bionetics, 1979). The first of these reported chromosome aberrations in Chinese hamster lung fibroblasts, the two Litton Bionetics studies used mouse lymphoma L5178Y cells. The results of all the studies were in agreement.

Trimethylsilanol has been tested for mutagenicity to mouse lymphoma cells up to cytotoxic concentrations according to a protocol that is similar to OECD 476 (1997) (Litton Bionetics, 1978). No increase in mutant frequency was observed in either the absence or presence of exogenous metabolic activation. Appropriate controls were included and gave expected results. It is concluded that the test substance is not mutagenic in mouse lymphoma L5178Y cells under the conditions of the test.

Litton Bionetics (1978) reported a test substance induced increase in sister chromatid exchanges per cell in L5178Y cells. As a clear dose response was not reported and this method is no longer used in the evaluation of mutagenicity, and in addition reliable data are available from in vitro and in vivo chromosome aberration studies, this result is ignored.

The same study also evaluate DNA damage using an elution technique: no evidence was found for test substance DNA damage in L5178Y cells.

The results obtained from the in vitro studies were confirmed when the substance was tested in vivo. In the key in vivo chromosome aberration assay, trimethylsilanol was tested in conducted according to a protocol that is similar to OECD 475 (Bioassay Systems Corporation, 1982). The test substance did not cause a statistically significant, dose related increase in chromosome breaks or aberrations when administered by intraperitoneal injection to Sprague Dawley rats up to the maximum tolerated dose. It is concluded that the test substance is not clastogenic in rat bone marrow cells under the conditions of the test.

A second in vivo chromosome aberration study is available (Litton Bionetics, 1984). The results of the key and supporting in vivo chromosome aberration studies are in agreement.

Data are available for mutagenicity to germ cells from a rodent dominant lethal assay in which trimethylsilanol was tested according to OECD 426 (1981), equivalent to OECD 478 (Dow Corning Corporation, 1983). The test substance was administered to male rats at three dose levels, for five days per week over eight week. No evidence of induction of chromosomal damage in germinal tissue was obtained from the study; there was no substance related effect on fertility index, per-implantation loss or resorption rate. A clear dominant lethal syndrome was evident in the positive control group. Although the test material was administered at a high enough level to induce transient sedation without toxicity, no reduction in male fertility or increase in dominant lethality was obtained. It is concluded that the test substance is negative for genetic toxicity to germ cells under the conditions of the test.

Justification for classification or non-classification

Based on the available in vitro and in vivo data, trimethylsilanol does not require classification for mutagenicity according to Regulation (EC) No 1272/2008.