Triethylsilane

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 S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 (OECD 471) (LPT, 2002).

Cytogenicity in mammalian cells: read across from tetramethylsilane: negative with and without metabolic activation in Chinese hamster lung fibroblasts (V79) (OECD 473) (Hüls, 1998).

Cytogenicity in mammalian cells: read across from trimethylsilane: negative with and without metabolic activation in CHL/IU cells (OECD 473) (Japan Bioassay Research Center, 2001).

Mutagenicity in mammalian cells: read across from tetramethylsilane: negative with and without metabolic activation in Chinese hamster ovary cells (OECD 476) (Hüls, 1999).

The studies were conducted according to appropriate OECD guidelines, or the Japanese equivalent and under GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Triethylsilane has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471 and in compliance with GLP (LPT, 2002). 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 102, TA 1535 or TA 1537 in the initial or the repeat experiments up to cytotoxic concentrations. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Information on cytogenicity is available from an assay using tetramethylsilane, which has been tested in a valid and reliable study according to OECD 473 and under GLP (Hüls, 1998). The volatility of the substance was taken into account in the study: exposure was in sealed flasks and an analytical determination of the concentrations by head space analysis was carried out at the end of the incubation period. No increase in the number of cells with aberrations was observed. Positive and vehicle controls produced expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of the test.

Further information on cytogenicity is available from a second surrogate substance, trimethylsilane, which has been tested according to a national standard method (Japanese) that is equivalent to OECD 473, and in compliance with GLP (Japan Bioassay Research Center, 2001). No increase in the incidence of chromosome aberrations was observed when tested using a gas exposure method at concentrations up to 80% with and without metabolic activation in Chinese hamster lung cells. Appropriate vehicle and positive controls were used and gave expected results. It is concluded that the test material is negative for the induction of chromosome aberrations under the conditions of the test.

Information on mutagenicity to mammalian cells comes from a study on the structural analogue tetramethylsilane, which has been tested in a valid and reliable study according to OECD 476 and under GLP (Hüls, 1999). The volatility of the substance was taken into account in the study: exposure was in sealed flasks and an analytical determination of the concentrations by head space analysis was carried out at the end of the incubation period. The statistically significant increase in the number of revertants was neither dose related nor exceeding historical negative control values, and the increase in the presence of metabolic activation was not reproducible. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint. 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. In the following paragraphs the proposed read-across from trimethylsilane and tetramethylsilane to triethylsilane is evaluated point by point. Further information is given in the report attached to section 13 PFA 2013aa.

Read-across hypothesis

The hypothesis is that source and target substances have similar toxicological properties because they are structurally similar and have similar physicochemical properties.

The substances are hydrolytically stable (triethylsilane, trimethylsilane and tetramethylsilane have half-lives in water of days) so reaction products do not need to be considered for the human health hazard assessment of these substances.

Triethylsilane reacts slowly in water with measured hydrolysis half-lives of 218 hours at pH 4 and 25°C, 377 hours at pH 7 and 20°C and 56.8 hours at pH 9 and 20°C in accordance with OECD 111. The products of hydrolysis are triethylsilanol and hydrogen.

Trimethylsilane reacts slowly in water, with a measured hydrolysis half-life of about 3 days at 24.7°C. The reaction products are trimethylsilanol and hydrogen

Tetramethylsilane has no structural groups that make it susceptible to hydrolysis, so it is stable in water.

Read-across justification

(a) Structural similarity

The registration and read-across substances are structurally similar and are members of an analogue group of alkylsilanes. All contain a silicon atom to which is attached three or four alkyl groups.

For the registered substance there are three ethyl groups, for trimethylsilane there are three methyl groups and for tetramethylsilane there are four methyl groups.

(b) Similar hydrolytic stability

Triethylsilane, trimethylsilane and tetramethylsilane are all hydrolytically stable (half-lives of days)

(c) Lack of structural alerts

None of the substances have structural alerts for genotoxicity (Benigni et al, 2008).

Tetramethylsilane and trimethylsilane were chosen as read-across substance as they are structurally similar to the registered substance and none of the substances has any functional groups that are associated with genetic toxicity. The genetic toxicity data available for other structurally similar substances are summarised in the table below.

Genetic toxicity data available for silanes

CASnumber	ECnumber	ChemicalName	Bacterial mutagenicity	In vitro mammalian cytogenicity	In vitro mammalian mutagenicity	In vivo genotox
75-76-3	200-899-1	Tetramethylsilane	Negative	Negative	Negative
617-86-7	210-535-3	Triethylsilane	Negative
631-36-7	211-155-0	Tetraethylsilane	No data
992-94-9	213-598-5	Methylsilane	No data
993-07-7	213-603-0	Trimethylsilane	Negative	Negative
7803-62-5	232-263-4	Silane	Positive* (+/- MA)
29681-57-0	n/a	t-butyl(dimethyl)silane	Negative	Negative

* This is a reliability 4 result (not assignable).

References:

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

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

Justification for classification or non-classification

Based on the available data on triethylsilane, tetramethylsilane and trimethylsilane, triethylsilane does not require classification for genetic toxicity according to Regulation (EC) No 1272/2008.