Registration Dossier

Administrative data

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 all strains tested (OECD TG 471) (RCC Cytotest Cell Research, 1998).
Cytogenicity in mammalian cells: negative with and without metabolic in Chinese lung fibroblasts (V79) (OECD TG 473) (BSL Bioservice, 2001e).
Mutagenicity in mammalian cells: read across from structural analogue triethoxyoctylsilane (2943-75-1): negative with and without metabolic activation in mouse lymphoma L5178Y cells (OECD TG 476) (BSL Bioservice, 2012).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Micronucleus assay oral study in mouse: Negative (OECD TG 474)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Information is available from reliable studies for in vitro mutagenicity to bacteria and cytogenicity, and from an in vivo micronucleus assay. No information is available for the registered substance for in vitro mutagencicity to mammalian cells, however, data are available for the structural analogue, triethoxyoctylsilane.

Non-testing methods including read-across from surrogate substances are able to provide information on mutagenic toxicity (REACH Guidance part 07a, R.7.7.3). In the case of genetic toxicity the presence or absence of functional groups that are known to be related to genetic toxicity is considered important, as the presence or absence of reactive groups and molecular substructures is associated with mutagenic and carcinogenic properties of chemicals (Benigni et al, 2008). Consideration is therefore given to the structural similarity, particularly presence or absence of structural alerts for genetic toxicity, when selecting surrogate substances for genetic toxicity endpoints.

Read-across hypothesis

The read-across hypothesis is that genetic toxicity depends on the molecular species to which the organism is exposed and the registered substance and the surrogate substance are structural analogues. Both are susceptible to hydrolysis and hydrolyse at comparable rates to structurally analogous silicon-containing hydrolysis products and a common non-silicon hydrolysis product.

Triethoxy(2,4,4-trimethylpentyl)silane hydrolyses to produce (2,4,4-trimethylpentyl)silanetriol and ethanol, with estimated hydrolysis half-lives of:

• Approximately 43 hours at pH 7 and 25°C;

• Approximately 16 hours at pH 7 and 37.5°C (relevant to in vitro assays, inhalation and dermal exposure, and to blood);

• Approximately 11 seconds at pH 2 and 37.5°C (relevant to oral exposure).

Triethoxyoctylsilane hydrolyses to produce octylsilanetriol and ethanol, with estimated hydrolysis half-lives of:

• Approximately 30 hours at pH 7 and 20-25°C;

• Approximately 11 hours at pH 7 and 37.5°C (relevant toin vitro assays, inhalation and dermal exposure, and to blood);

• Approximately 9 seconds at pH 2 and 37.5°C (relevant to oral exposure).

Read-across justification

(a) structural simlarity: Both triethoxyoctylsilane and triethoxy(2,4,4-trimethylpentyl)silane are triethoxysilanes with an alkane side-chain containing eight carbons; the only difference is that the side-chain in triethoxyoctylsilane is linear and the side-chain in triethoxy(2,4,4-trimethylpentyl)silane is branched.

(b) similar hydrolysis rates: both substances hydrolyse at intermediate rate at neutral pH. At high (and low) pH, relevant to oral exposure, both substances hydrolyse rapidly forming closely related silicon-containing hydrolysis products.

(c) lack of structural alerts: neither of the substances has structural alerts for genotoxicity (Benigni et al, 2008).

(d) the second hydrolysis product of the substances, ethanol, is the same for both substances and is not genotoxic (OECD 2004).

Triethoxy(2,4,4-trimethylpentyl)silane has been tested in a valid and reliable study conducted according to OECD TG 471 and in compliance with GLP (RCC Cytotest Cell Research, 1998). No mutagenic effect was observed for the test substance tested up to limit concentration in any of the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in a plate incorporation experiment without and with metabolic activation. The result was confirmed in an independent pre-incubation assay. Appropriate positive, negative 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.

Triethoxy(2,4,4-trimethylpentyl)silane has been tested in a valid and reliable test performed according to OECD TG 473 in compliance with GLP (BSL Bioservice, 2001e). The test substance did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line with and without metabolic activation up to limit concentrations. Appropriate solvent and postive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of the test.

An additional study on in vitro cytogenicity is available (CERI, 2001). This study reported a positive in Chinese hamster fibrobalsts (V79 cells) in the absence of metabolic activation. The study report available for this result is an extended summary, and does not include tables of results, so there is not enough information to for a full independent assessment, but it is noted by the reviewer that the test substance was much more cytotoxic in the absence of activation, and the increase in abnormalities recorded was most marked at cytotoxic concentrations. In addition, the test substance is reported to be a mixture of . In view of these factors, the availability of a reliable negative result in a similar study and the negative result in vivo, the study with the negative result was chosen as key.

Information on mutagenicity to mammalian cells is available for the structural analogue triethoxyoctylsilane which has been tested in a reliable study conducted according to OECD TG 476 and in compliance with GLP (BSL Bioservice, 2012). No biologically relevant increase in mutation rate was found in mouse lymphoma L5178Y cells with or without metabolic activation in either the initial or the repeat experiment, up to limit and cytotoxic concentrations. The global evaluation factor was not exceeded at any concentration. In addition, colony sizing showed no clastogenic effects in either experiment. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.

Triethoxy(2,4,4-trimethylpentyl)silane has been tested in a reliable in vivo mouse micronucleus assay according to OECD 474 and under GLP (Bioservice, 2001). No statistically significant increase in the number of cells with micronuclei was observed after oral administration of the limit dose of 2000 mg/kg bw. Appropriate positive and vehicle controls were included and gave expected results. The PCE / NCE ratio was slightly affected in treated males, indicating that the test item was of low toxicity to the target tissue. It is concluded that the test substance is negative for the induction in micronuclei under the conditions of the test.

Benigni et al (2008). The Benigni/Bossa rule base for mutagenicity and carcinogenicity JR Scientific report EUR 23241 EN

OECD (2004): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 19-22 October 2004, Ethanol, CAS 64-17-5.

PFA (2013aa). Peter Fisk Associates, Genotox Analogue Report, PFA.300.004.001.


Justification for classification or non-classification

Based on the available in vitro data and in vivo data on the registered substance and its structural analogue, triethoxy(2,4,4-trimethylpentyl)silane is not classified for mutagenicity according to Regulation (EC) No. 1272/2008.