Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

An Ames test is available for the registered substance trimethoxy(propyl)silane (CAS 1067-25-0). No data are available to assess the in vitro mammalian mutagenicity and cytogenicity of trimethoxy(propyl)silane (CAS 1067-25-0); however, reliable in vitro and in vivo data are available for the structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1). Both substances hydrolyse in the stomach with half-lives of 2.6 h for the registered substance trimethoxy(propyl)silane (CAS 1067-25-0) at pH 7 and 20-25°C and 30 h for the structural analogue substance trimethoxy(propyl)silane (CAS 1067-25-0) at pH 7 and 25°C.Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT50 (XºC) = DT50 (T) x e(0.08 (T-X))

Where T = temperature for which data are available and X = target temperature.

Thus, for trimethoxy(propyl)silane (CAS 1067-25-0) the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 0.81 h.

For the read-across substance, triethoxy(isobutyl)silane (CAS 17980-47-1), the corresponding half-life is approximately 11.04 h, respectively.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered. Thus, at conditions present in the stomach (pH 2 and 37.5°C) the hydrolysis half-lives are 5 and 9 sec for the registered substance and the surrogate, respectively.

Therefore, hydrolysis is expected to occur during testing and following exposure. The silanol-containing hydrolysis products are close structural analogues: propylsilanetriol and (2-methylpropyl)silanetriol. The further products of hydrolysis are methanol and ethanol, respectively. Since neither methanol nor ethanol would contribute to genetic toxicity effects in rodents at the dose levels tested, it is considered that the observed toxicological effects are due to the action of the silicon-containing moiety, although neither substance has any functional groups that are associated with genetic toxicity. Therefore, studies performed with triethoxy(isobutyl)silane (CAS 17980-47-1) were considered appropriate for read-across to trimethoxy(propyl)silane (CAS 1067-25-0). Additional information is given in a supporting report (PFA, 2013aa) attached in Section 13 of the IUCLID 5 dossier. The genetic toxicity data available for other read-across substances are summarised in Table 1.

Table1: Summary of available genotoxicity data for substances in group I-2.

CAS

Name

Bacterial Mutagenicity

In Vitro Mammalian Cytogenicity

In Vitro Mammalian Mutagenicity

In Vivo Genotox

000998-30-1

Triethoxysilane

 

 

Negative

 

002031-62-1

Diethoxy(methyl)silane

Negative

 

 

 

001112-39-6

Dimethoxydimethylsilane

Negative

Negative

 

 

000078-62-6

Diethoxy(dimethyl)silane

Negative

Negative

Negative

 

001185-55-3

Trimethoxy(methyl)silane

Negative

Positive

Positive

Negative in micronucleus

002031-67-6

Triethoxy(methyl)silane

Negative

Negative

Negative

 

001825-62-3

Ethoxytrimethylsilane

Negative

 

 

 

001066-40-6

Hydroxytrimethylsilane

Negative

Negative

Negative

Negative in chromosome aberration and rodent dominant lethal

031795-24-1

Potassium methylsilanetriolate

Negative

 

 

 

001067-25-0

Trimethoxy(propyl)silane

Negative

 

 

 

018395-30-7

Trimethoxy(2-methylpropyl)silane

Negative

 

 

 

017865-32-6

Cyclohexyldimethoxymethylsilane

Negative

 

Negative

Positive in micronucleus, negative in rodent dominant lethal

017980-47-1

Triethoxy(isobutyl)silane

Negative

Negative

Negative

micronucleus

034396-03-7

Trimethoxy(2,4,4-trimethylpentyl)silane

Negative

 

 

 

035435-21-3

Triethoxy(2,4,4-trimethylpentyl)silane

Negative

Negative

 

Negative in micronucleus

126990-35-0

Dicyclopentyldimethoxysilane

Negative

Negative

 

Negative in micronucleus

003069-40-7

Trimethoxyoctylsilane

Negative

 

 

 

085712-15-8

Dimethoxymethyloctylsilane

Negative

 

 

 

002943-75-1

Triethoxyoctylsilane

Negative

Negative

 

 

016415-12-6

Hexadecyltrimethoxysilane

Negative

Negative

 

 

070851-50-2

Dimethoxymethyloctadecylsilane

Negative

 

 

 

002487-90-3

Trimethoxysilane

Negative

Negative

 

Negative in micronucleus

016068-37-4

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Negative

Equivocal

 

Negative in micronucleus

029043-70-7

Dimethylbis(octadecyloxy)silane

Negative

 

 

 

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment.

A key bacterial mutagenicity study according to OECD TG 471 and GLP is available for the registered substance. No evidence for a test-substance related increase in the number of revertants was observed when tested up to cytotoxic concentration in any of the Salmonella typhimurium strains (TA 1535, TA1537, TA98 and TA100) in two independent experiments without and with metabolic activation. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, the registered substance was concluded to be non-mutagenic in the strains tested (Hüls AG, 1996).

No data are available for mutagenicity to a bacterial strain capable of detecting cross-linking or oxidising mutagens. In view of the lack of genetic toxicity demonstrated in studies on mammalian cells, and the absence of structural features that indicate that such mutagenicity is likely, testing in an appropriate 5th strain is not considered necessary. In addition, the only silicon-containing substance which has given a positive result in a bacterial strain capable of detecting cross-linking or oxidising mutagens contains an epoxy- side-chain (which is associated with cross-linking mutagenicity), and this substance was positive in Salmonella typhimurium strains TA 100, TA 1535 as well as in E.coli WP2 uvrA.

The key in vitro cytogenicity study on the structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1) was conducted according to OECD TG 473. No increase in the number of cells with aberrations was observed either with or without activation up to cytotoxic concentrations in Chinese hamster lung fibroblasts (V79). Appropriate concurrent negative and positive controls were included and the expected responses were observed. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study (Hüls AG, 1992).

 

A key in vitro mammalian cell gene mutation study according to OECD TG 476 is available for the structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1). No statistically and biologically significant increase in the mutant frequency was observed in Chinese hamster ovary cells tested with and without metabolic activation. Appropriate concurrent negative and positive controls were included and the expected responses were observed. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test (Hüls AG, 1991).

   

A key in vivo mouse micronucleus study according to OECD TG 474 is available for the structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1). No evidence for an increase in the incidence of micronucleated normochromatic erythrocytes in mice bone marrow. It is concluded that the test substance did not cause damage to chromosomes under the conditions of the test (Huntingdon Research Centre, 1988).

 

Therefore, with regard to the presented data, the registered substance is assumed to have neither mutagenic nor cytogenic potential


Justification for selection of genetic toxicity endpoint
No study was selected, since all available studies were negative.

Short description of key information:
Only a reliable bacterial mutagenicity study is available for trimethoxy(propyl)silane, however, reliable data are available for the structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1) for in vitro cytogenicity, in vitro mammalian gene mutation and in vivo micronucleus.

In vitro:

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA 98, TA, 100, TA 1535 and TA 1537 (according to OECD TG 471).

Cytogenicity in mammalian cells: read-across from structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1): negative in Chinese hamster lung fibroblasts (V79) (OECD TG 473).

Mutagenicity in mammalian cells: read-across from structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1): negative in CHO cells (OECD TG 476)

In vivo:

Single oral exposure to 8800 mg/kg in mouse: read-across from structural analogue substance triethoxy(isobutyl)silane (CAS 17980-47-1): Micronucleus assay negative for chromosomal aberration (OECD TG 474)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo data on mutagenicity of the registered substance and the structural analogue substance, triethoxy(isobutyl)silane (CAS 17980-47-1), trimethoxy(propyl)silane is not classified for mutagenicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.