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Administrative data

Key value for chemical safety assessment

Additional information

Information is available for 3-(diethoxymethylsilyl)propylamine from reliable in vitro studies on mutagenicity to bacteria and cytogenicity to mammalian cells. No information is available for other in vitro or in vivo genetic toxicity endpoints for 3-(diethoxymethylsilyl)propylamine, however, studies are available for the related substance 3-aminopropyltriethoxysilane (CAS 919-30-2). 3-(diethoxymethylsilyl)propylamine and 3-aminopropyltriethoxysilane hydrolyse to 3-(dihydroxymethylsilyl)propylamine and aminopropylsilanetriol respectively. The other product of hydrolysis of both substances is ethanol, which is not expected to contribute to genetic toxicity (OECD 2004b)). 3-(diethoxymethylsilyl)propylamine hydrolyses rapidly at physiological pH (hydrolysis half-life 6 h at pH 7 (measured)) 3-aminopropyltriethoxysilane also hydrolyses rapidly at physiological pH (hydrolysis half-life 8.5 h at pH 7 (measured)). It is therefore considered appropriate to read across the genetic toxicity results for 3-aminopropyltriethoxysilane to the registered substance because the silanol products of hydrolysis are closely related and both substances have similar functional groups, and the differences are not expected to make a difference to genetic toxicity. Additional information is given in a supporting report (PFA (2013aa)) attached in Section 13 of the IUCLID 5 dossier. 3-aminopropyltriethoxysilane.was chosen as the read-across substance as it has a silanol hydrolysis product that includes a propylamine group attached to the silicon, and neither substance has functional groups that are associated with genetic toxicity. The differences between the dihydroxymethylsilyl and trisilanol hydrolysis products is not considered to be relevant to genetic toxicity, as no association between mono- di- or trisilanols and genotoxicity has been observed. 3-(diethoxymethylsilyl)propylamine been tested in a reliable study conducted according to a Japanese standard method that is similar to OECD 471 and under GLP (Hita Research Laboratory (2003)). No test-substance related increase in the number of revertants was observed for the substance tested up to cytotoxic concentration in Salmonella typhimurium strains TA 100, TA 1535, TA 98, TA 1537, and E. coli WP2uvrA in either of two independent experiments without and with metabolic activation using the pre-incubation method. Appropriate solvent and positive 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.

An additional bacterial mutagenicity study is available (Kennelly JC (1988)). Negative results were obtained when 3-(diethoxymethylsilyl)propylamine was tested in Salmonella typhimurium strains TA 97, TA 98 and TA 100. This study was considered to be reliability 4 as only three strains of bacteria were tested, and only 2-aminoanthracene was used as the positive control in the presence of metabolic activation. The more reliable study was selected as key.

Information on potential for cytogenicity is available from a reliable study on 3-(diethoxymethylsilyl)propylamine conducted according to a Japanese standard method that is equivalent to OECD 473 and under GLP conditions (Shyouzou (2003)). Dose related increases in the number of CHL/IU cells with aberrations were observed with and without metabolic activation. It was observed that the pH of the culture medium increased at higher concentrations of test material, so the test was repeated with a more strongly buffered test medium. It was still not possible to control the pH of the cell growth medium fully. It was the opinion of the author of the report (as summarised by a Japanese speaker) that although the pH was increased in cultures showing increased frequency of cells with chromosome aberrations, as the effect was seen both with and without metabolic activation, this did not invalidate the positive result and the test material was concluded to be clastogenic.

The structural analogue substance, 3-aminopropyltriethoxysilane, has been tested in a reliable mammalian mutagenicity assay according to OECD TG 476 and under GLP (Krueger N (1998)). The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2. Expected results were obtained from medium and positive controls. The results from the repeat experiment were consistent with those from the initial test. No increase in the mutant frequency was observed in Chinese hamster Ovary (CHO) cells in the absence of activation. In the presence of activation, a statistically significant increase was observed at a single concentration. As this result was within the range of the mutant frequencies of the historical negative controls, and no dose response relationship was observed, the increases are a result of normal assay variation rather than a mutagenic effect of the test substance. It is the opinion of the reviewer that although the test substance hydrolyses in water, and so the use of aqueous cell culture medium may have led to exposure of the test organisms to the products of hydrolysis rather than the test substance itself, this does not invalidate the test, as hydrolysis would occur in exposed organisms. It is concluded that the test substance in not mutagenic to mammalian cells under the conditions of the test.

3 -Aminopropyltriethoxysilane (Silane A-1100 CAS No. 919-30-2) has been tested in a reliable mouse micronucleus assay according to a protocol that is similar to OECD TG 474 and under GLP (BRRC (1998)). No treatment related increases in numbers of micronuclei in PCEs in Swiss-Webster mice were observed. Relatively high dose levels of the substance were tested by intraperitoneal administration up to 80% of the LD50 with no indication of a positive induction of micronuclei. The test substance was considered to be inactive as a clastogenic agent under the statistical criteria used. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of the test.

Although an increase in cells with aberrations was observed in vitro, no effect was observed when the analogous substance was tested in an in vivo micronucleus assay, so it is concluded that 3-(diethoxymethylsilyl)propylamine is not genotoxic.


Short description of key information:
Information is available for 3-(diethoxymethylsilyl)propylamine from reliable in vitro studies on mutagenicity to bacteria and cytogenicity to mammalian cells. No information is available for other in vitro or in vivo genetic toxicity endpoints for 3-(diethoxymethylsilyl)propylamine, however, studies are available for the related substance 3-aminopropyltriethoxysilane (CAS 919-30-2).

In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WP2 (similar to OECD TG 471) (Hita Research Laboratory (2003)).
Cytogenicity in mammalian cells: positive with and without metabolic activation in CHL/IU cells (similar to OECD TG 473) (Shyouzou (2003)).
Mutagenicity in mammalian cells: read across from analogous substance CAS 919-30-2: negative in CHO K1 cells (OECD TG 476) (Krueger N (1998)).

In vivo:
Micronucleus assay: read across from analogous substance 3- aminopropyltriethoxysilane CAS 919-30-2: Negative (ip study in mouse) (similar to OECD TG 474) (BRRC (1998)).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo genotoxicity data, 3-(diethoxymethylsilyl)propylamine is not classified for mutagenicity according to Regulation (EC)1272/2008.