N-(3-{1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]trisiloxan-3-yl}propyl)prop-2-enamide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-11-20 to 2010-02-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP-study according to recent OECD technical guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Copy of GLP certificate is attached to full study report

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-(3-{1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]trisiloxan-3-yl}propyl)prop-2-enamide

EC Number:

700-253-3

Cas Number:

115258-10-1

Molecular formula:

C15H37NO4Si4

IUPAC Name:

N-(3-{1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]trisiloxan-3-yl}propyl)prop-2-enamide

Method

Target gene:

TA 98: His D3052, TA 100: His G46, E.coli: Trp, TA 1535: His G46, TA 1537: His C3076

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

S9 fraction from Aroclor induced rats

Test concentrations with justification for top dose:

62µg, 185µg, 556µg, 1667µg, 5000µg

Vehicle / solvent:

- Solvent: Ethanol/water 95% w/w

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA98 w/o S9, solvent DMSO

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100 and TA1535, both w/o S9, solvent H2O

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 w/o S9, solvent DMSO

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

E. Coli WP2 w/o S9, solvent DMSO

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

All strains with S9, solvent DMSO

Details on test system and experimental conditions:

Please see "Any other information on material and methods incl. tables"

Evaluation criteria:

The number of colonies per plate was counted with an automatic colony counter. Data are presented in tables as the number of colonies present per plate (mean +/- standard deviation).
A result will be considered positive, when R>2.5
The ration R is calculated as follows:
R = Number of revertant colonies in presence of the test item / Number of revertant colonies in absence of the test item
Several criteria are used for determining a positive result: a dose-response in the range tested and/or a reproducible increase at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without metabolic activation system.
Historical negative (solvent/vehicle) and positive control values are represented in the attached document.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

- Sterility test showed no contamination during the study
- No cytotoxic effect was observed
- The controls (positive and negative) were in concordance with the expected results
- Positive and negative controls showed absolute numbers of revertant colonies comparable to historical data
- No concentration of the test item showed a biological significant increase of the number of revertant either with or w/o S9 metabolic activation
- No dose-response was observed in none of the tested bacterial strains

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

The results of the mutagenicity test are included in the attached documents.

The controls of the test were in concordance with the expected results:

−       Sterility test showed no contamination during the study.

−       No cytotoxic effect was observed.

−       All positive controls performed showed valid ratios (R) above 2.5.

−       Positive and negative controls showed absolute numbers of revertant colonies comparable to historical data.

−       No concentration of the test item showed a biological significant increase (R ≥ 2.5) of the number of revertant either with or without S9 metabolic activation.

−       No dose response was observed in none of the tested bacterial strains.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The following conclusions can be inferred from the obtained results:
− No experiment with the test item showed ratios (R) above 2.5 as compared to the negative control, either with or without S9 metabolic activation.
− No dose response was observed in none of the tested bacterial strains.
Based on the results obtained in this study, the test item N-[3-tris(trimethylsilyloxy)silylpropyl]prop-2-enamide was found to be NON MUTAGENIC and NON PRO-MUTAGENIC under the test conditions.

Executive summary:

The present bacterial reverse mutation test (Ames test) was performed in order to evaluate the mutagenic potential of the test item.

The test was performed in accordance with OECD Guideline 471 for the Testing ofChemicals (Bacterial Reverse Mutation Test. Adopted 21^stJuly 1997) and the test Method B13/B14 of Commission Directive 2000/32/EC.

Doses ranging from 5000µg to 62µg per plate were tested. No cytotoxicity was observed at any dose.

Suspensions of 4 amino-acid requiring strains of Salmonella typhimurium (TA98, TA100,TA1535, TA1537) and one Escherichia coli WP2 strain (pKM 101) auxotroph for an amino acid were exposed by the direct plate incorporation method to five doses of the test item in the presence and in the absence of an exogenous metabolic activation system. Both tests were repeated with the pre-incubation method.

Revertant bacteria due to point or frameshift-mutations at specific locus are able to grow,forming colonies. These colonies were counted and compared to the number of spontaneousrevertant colonies on solvent control plate (negative control). Similarly, specific standard mutagens were tested and used as positive controls.

Based on  the results obtained in this study, the test item N-[3 -tris(trimethylsilyloxy)silylpropyl]prop-2-enamide was found to be NON MUTAGENICand NON-PROMUTAGENIC under the test conditions.