Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic toxicity in vitro:

Gene mutation (Bacterial reverse mutation assay / Ames test, RA from CAS 2031-62-1): S. typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 102: negative with and without metabolic activation (according to OECD 471)

Mammalian cytogenicity (Chromosome Aberration, RA from CAS 75-78-5): negative with and without metabolic activation (similar to OECD 473)

Gene Mutation (Mammalian Cells, RA from CAS 75-78-5): negative with and without metabolic activation (similar to OECD 476)


Genetic toxicity in vivo:
no data available

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100, TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
up to limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 90, TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
TA 1537, reduced colony numbers in the highest dose group
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
reduced colony numbers in the highest dose
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: CAS 2031-62-1
Conclusions:
The source substances showed no genotoxic potential in bacteria. As explained in the analogue justification a similar genotoxicity potential in bacteria is assumed for the target substance.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Remarks:
toxicity was measured but the results not reported.
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Remarks:
toxicity was measured but the results not reported
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: CA, CAS 75-78-5
Conclusions:
The source substance showed no genotoxic potential in a chromosome aberreation assay and sister chromatid exchange assay. As explained in the analogue justification a similar genotoxicity potential in mammalian cells is assumed for the target substance as well.
Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below
Reason / purpose:
read-across source
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
0.64 µl/ml with activation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Conclusions:
The source substance showed no genotoxic potential in mammalian cells. As explained in the analogue justification a similar genotoxicity potential in mammalian cells is assumed for the target substance as well.


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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment. Other available data are included as supporting studies.

No information is available for the registered substance dimethoxymethylsilane, however, reliable data are available for the closely related substances, diethoxymethylsilane (CAS 2031-62-1) and dichlorodimethylsilane (CAS 75-78-5).

The silicon-containing products of hydrolysis are close structural analogue silanoles: dimethoxymethlsilane, diethoxymethylsilane and dichlorodimethylsilane hydrolyse to methylsilanediol and –triol (both diethoxy- and dimethoxymethylsilane) and dimethylsilanediol, respectively. All 3 substances hydrolyse rapidly and hydrolysis is expected to occur during testing and following exposure. It is therefore considered appropriate to read-across the in vitro genotoxicity from dichlorodimethylsilane (CAS 75-78-5) and diethoxymethylsilane (CAS 2031-62-1) to the registered substance.

 

The key bacterial mutagenicity study on diethoxymethylsilane (CAS 2031-62-1) was conducted in compliance with GLP and according to OCED TG 471. No evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 102. The strains were treated with doses of 31.6 to 5000 µg/plate with and without metabolic activation system and in a plate-incorporation and a pre-incubation assay. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, diethoxymethylsilane was concluded to be non-mutagenic in the Salmonella typhimurium strains (BSL BIOSERVICE, 2007c).

 

This conclusion was further supported by an additional, less reliable bacterial reverse mutation assay conducted with dichlorodimethylsilane (CAS 75-78-5) equivalent or similar to OECD 471 prior to GLP commencement. No test-substance related increase in the number of revertants was observed in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 when treated with doses of 0.001 to 5 µl/plate with and without metabolic activation system (Litton Bionetics, 1978b).

 

The key in vitro cytogenicity study on dichlorodimethylsilane (CAS 75-78-5) was conducted equivalent or similar to OCED TG 473 (only 100 cells were counted) and prior to the commencement of GLP. Dichlorodimethylsilane did not cause a statistically significant, dose related increase in chromosome aberrations in mouse lymphoma L5178Y cells with or without metabolic activation. The test substance was therefore considered non-clastogenic in mouse lymphoma L5178Y cells. Appropriate positive and solvent controls were included and gave expected results (Litton Bionetics, 1980).

 

A key mammalian cell gene mutation study equivalent or similar to OECD TG 476 and which was conducted prior to the commencement of GLP is available for dichlorodimethylsilane (CAS 75-78-5) . The substance was tested in the mouse lymphoma L5178Y cells in the absence and presence of metabolic activation. The cultures selected for cloning were treated with doses up to 0.32 µl/ml in the absence and 0.64 µl/ml in the presence of metabolic activation and exhibited no mutagenic potential in mouse lymphoma L5178Y cells. Appropriate positive and solvent controls were included and gave expected results (Litton Bionetics, 1978a). 

 

Additionally, a mammalian cell genotoxicity study equivalent or similar to OECD 479 (only 40 metaphases counted), detecting SCEs was conducted with dichlorodimethylsilane (CAS 75-78-5). The substance was tested in mouse L5178Y cells with doses up to 0.32 µl/ml in the absence and 0.64 µl/ml in the presence of metabolic activation. It induced a slight increase with metabolic activation compared to the control at the 5% level only. Since there is a clear dose response for the solvent (ethanol) alone together with metabolic activation, it can be assumed that this effect is due to drying agents (e.g. benzene) used in preparation of absolute ethanol and the slight increase seen with the test substance diluted in 1% ethanol are hence not considered a real effect. Therefore, the test material can be considered negative under the conditions of the test (Litton Bionetics Inc., 1980). 

 

In conclusion, since there is no evidence for mutagenic or genotoxic effects of structural analogues diethoxymethylsilane (CAS 2031-62-1) and dichlorodimethylsilane (CAS 75-78-5), the registered substance dimethoxymethylsilane is considered not to have mutagenic potential.

  

In vivo testing is not required as no evidence for genetic toxicity was found in the in vitro studies.

Justification for classification or non-classification

Based on the available in vitro data on mutagenicity from the structural analogues diethoxymethylsilane and dichlorodimethylsilane, the registered substance dimethoxymethylsilane is not classified for mutagenicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.