Trimethoxy(2-methylpropyl)silane

Endpoint summary

Additional information

There are data available for bacterial mutagenicity from two reliable studies for trimethoxy(2-methylpropyl)silane (2 -methylpropyl and isobutyl are synonyms). For the remaining in vitro endpoints, data are available for the related substance, triethoxyisobutylsilane CAS 17980-47-1. The results of all the studies were in agreement. Trimethoxy(2-methylpropyl)silane and triethoxyisobutylsilane share a common hydrolysis product, 2 -methylpropylsilanetriol, although triethoxyisobutylsilane will hydrolyse more slowly (predicted to be approximately 22 hours) compared with the rapid rate of the registration substance. This is not expected to affect genetic toxicity as hydrolysis is likely to occur under test conditions and in vivo. It is considered appropriate to read across the genetic toxicity results for triethoxyisobutylsilane to trimethoxyisobutylsilane as both substances share similar functional groups and the differences are not expected to contribute to their genetic toxicity, as neither methanol nor ethanol are genotoxic (OECD (2004a), (2004b)). Additional information is given in a supporting report (PFA (2013aa)) attached in Section 13 of the IUCLID 5 dossier.

Triethoxyisobutylsilane was chosen as read-across substance as it has the same hydrolysis product as the registered substance and neither substance has any functional groups that are associated with genetic toxicity. The genetic toxicity data available for other read-across substances are summarised in the Table below. Only two of the trimethoxy substances have any indication of potential for genetic toxicity; these were not selected for read across as the results observed in vitro were not confirmed when tested in vivo, and there are closer structural analogues that are more appropriate for read across.

CAS	Name	Bacterial Mutagenicity	In Vitro Mammalian Cytogenicity	In Vitro Mammalian Mutagenicity	In Vivo Genotox
1067-25-0	Trimethoxypropylsilane	Negative Ebert R (1996a)	-	-	-
1185-55-3	Trimethoxy(methyl)silane	Negative Wagner VO, Klug ML (2004)	Positive +MA Not cytotoxic Gudi R, Rao M (2004)	Positive +MA Not cytotoxic Steenwinkel M-J S T (2002)	Negative in micronucleus Research Toxicology Centre (2002)
2031-67-6	Triethoxy(methyl)silane	Negative Hazleton France (1992)	Negative Litton Bionetics (1979)	Negative Litton Bionetics (1978)	-
2487-90-3	Trimethoxysilane	Negative Wagner VO (1995)	Negative Gudi R, Rao M (2007)		Negative in micronucleus Isquith, A.J; Groh, C.L (1982)
2768-02-7	Trimethoxyvinylsilane	Negative MHLW (2005a)	Positive +MA Not cytotoxic MHLW (2005b)	Negative Ebert, R. (1996b)	Negative in micronucleus Slesinski, R. (1985)
3069-40-7	Trimethoxyoctylsilane	Negative Dow Corning (2003)	-	-	-
2943-75-1	Triethoxyoctylsilane	Negative Wagner, V O, Twardzik S C (1998)	Negative MA Bioservices, Inc (1997)	Negative Zeller, J (2012)	-
18395-30-7	Trimethoxy(2-methylpropyl)silane	Negative Dow Corning Corporation (1987c)	-	-	-
17980-47-1	Triethoxyisobutylsilane	Negative Hüls (1992)	Negative May C (1992)	Negative Ebert R (1991)	Negative in micronucleus Huntingdon Research Centre, (1988)

A reliable bacterial mutagenicity study was conducted according to draft protocols 419 and 420 which are similar to OECD TG 471 in which no evidence of mutagenicity was observed with or without metabolic activation when trimethoxy(2-methylpropyl)silane was tested in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA1537 and E. coli WP2. (Dow Corning 1987c). A supporting study (Schoberl 1994) gave the same result using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538. This more recent study was not selected as the key study as the range of strains does not comply with the current guideline.

A reliable cytogenicity study was conducted according to OECD TG 473 and under GLP, with no evidence of the induction of chromosome aberration by the read-across substance, triethoxyisobutylsilane, when tested with or without metabolic activation in Chinese hamster lung fibroblasts (V79) (May 1992).

A reliable mutagenicity study was conducted according to OECD TG 476 and under GLP, with no evidence of the induction of mutations by the read-across substance, triethoxyisobutylsilane, when tested with or without metabolic activation in Chinese hamster ovary cells (Ebert 1991).

The read-across substance, triethoxyisobutylsilane (CAS 17980 -47 -1) was tested in a reliable in vivo micronucleus assay in mouse conducted according to OECD 474. No evidence for the induction of micronuclei after a single oral exposure to 8800 mg/kg bw was observed (Huntingdon Research Centre 1988).

Justification for selection of genetic toxicity endpoint
The selected bacterial mutagenicity was selected as key study although older and of the same reliability as the other study available, but includes a strain capable of detecting cross-linking mutagens. It was conducted in accordance with a protocol similar to an appropriate OECD test guidelines and in compliance with GLP. The in vitro mammalian studies are the only available in vitro mutagenicity and cytogenicity studies available for the surrogate substance. The in vivo micronucleus study was the more reliable of the two in vivo studies available for the surrogate substance. The in vitro and in vivo mammalian studies were conducted in accordance with appropriate OECD test guidelines and in compliance with GLP.

Short description of key information:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in all strains tested (similar to OECD TG 471) (Dow Corning 1987c)
Cytogenicity in mammalian cells: read-across from analogous substance Triethoxyisobutylsilane CAS 17980-47-1: negative in Chinese hamster lung fibroblasts (V79) (OECD TG 473) (May 1992)
Mutagenicity in mammalian cells: read-across from analogous substance Triethoxyisobutylsilane CAS 17980-47-1: negative in CHO cells (OECD TG 476) (Ebert 1991)

In vivo:
Micronucleus assay (oral exposure to 8800 mg/kg in mouse): read-across from analogous substance Triethoxyisobutylsilane CAS 17980-47-1: negative for induction of micronuclei (OECD 474) ( Huntingdon Research Centre 1988)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo genotoxicity data, trimethoxy(2-methylpropyl)silane is not classified for mutagenicity according to Regulation 1272/2008/EC