Tris(isopropenyloxy)vinylsilane

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:

13 Feb 2015 to 20 March 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

tris(isopropenyloxy)(vinyl)silane

IUPAC Name:

tris(isopropenyloxy)(vinyl)silane

Constituent 2

Reference substance name:

Tris(isopropenyloxy)vinylsilane

EC Number:

239-362-1

EC Name:

Tris(isopropenyloxy)vinylsilane

Cas Number:

15332-99-7

Molecular formula:

C11H18O3Si

IUPAC Name:

[tris(isopropenyloxy)vinyl]silane

Test material form:

other: liquid

Method

Target gene:

histidine operon

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital and β-naphthoflavone induced rat liver S9

Test concentrations with justification for top dose:

pre-experiment: 0.00316, 0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 μl/plate
main experiments: 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 μl/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: aqueous solvent was in appropriate due to the hydrolytic instability of the substance. The solvent was compatible with the survival of the bacteria and the S9 activity

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

distilled water

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100, TA 1535; 10 μg/plate; -MA

Controls 2

Untreated negative controls:

yes

Remarks:

distilled water

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylene-diamine (4-NOPD)

Remarks:

TA 98 (10 μg/plate), TA 1537 (40 μg/plate); -MA

Controls 3

Untreated negative controls:

yes

Remarks:

distilled water

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

TA 102; 1 μl/plate; -MA

Controls 4

Untreated negative controls:

yes

Remarks:

distilled water

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (2-AA)

Remarks:

all strains; 2.5 μg/plate (10 μg/plate for TA 102); +MA

Details on test system and experimental conditions:

ACTIVATION:
Phenobarbital and β-naphthoflavone induced rat liver S9
Protein concentration: 38.2 mg/ml adjusted to 25 mg/ml
S9 mix:
- 100 mM sodium-ortho-phosphate-buffer, pH7.4
- 8 mM MgCl2
- 22 mM KCl
- 5 mM glucose-6-phosphate
- 4 mM NADP

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 60 min at 37°C
- Selection time (if incubation with a selection agent): at least 48h at 37°C in the dark

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: 3 plates per concentration; the experiment was repeated. The initial assay was conducted using the plate incorporation method, the repeat experiment used pre-incubation.

DETERMINATION OF CYTOTOXICITY
- Method: other: clearing or diminution of the background lawn or a reduction in the number of revertants down to a mutation factor of approximately ≤0.5 in relation to the solvent control

OTHER:

Evaluation criteria:

A test item is considered mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs
in at least one tester strain with or without metabolic activation.

A biologically relevant increase is:
- if in strains TA 98, TA 100 & TA 102, the number of reversions is at least twice as high
- if in strains TA 1535 & TA 1537, the number of reversions is at least three times as high

Statistics:

A statistical evaluation is not regarded as necessary.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Plate incorporation - mean number of revertants (3 plates)

Dose (µl/plate)	TA 98		TA 100		TA 1535		TA 1537		TA 102
	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA
Negative control	16	25	69	96	9	9	6	6	246	287
Solvent control	13	18	67	79	8	9	5	4	210	284
0.0316	17	22	65	85	13	11	7	7	193	275
0.100	18	19	61	74	11	13	6	6	201	281
0.316	16	22	57	80	11	9	7	4	206	270
1.0	14	26	53	87	10	11	5	3	204	292
2.5	20	27	64	88	9	8	7	4	204	291
5.0	20	26	70	93	14	8	5	6	220	286
Positive control	326	2361	285	2424	846	182	66	211	2714	762

Table 2: Preincubation - mean number of revertants (3 plates)

Dose (µl/plate)	TA 98		TA 100		TA 1535		TA 1537		TA 102
	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA	-MA	+MA
Negative control	24	23	83	106	12	14	5	5	237	383
Solvent control	19	22	65	88	12	13	4	4	162	277
0.0316	17	32	68	100	17	12	4	9	214	369
0.100	20	22	75	87	15	10	8	7	174	337
0.316	15	23	66	95	15	14	4	5	161	329
1.0	19	23	73	95	19	12	4	3	130	319
2.5	23	28	64	90	15	12	3	6	105	307
5.0	18	24	87	94	12	12	2	7	253	386
Positive control	856	868	527	1598	1158	210	69	155	2094	725

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

Tris(isopropenyloxy)(vinyl)silane has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD TG 471, compliant with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or TA 102 in the initial plate incorporation assay or the repeat experiment using the pre-incubation method, up to limit concentrations. Appropriate positive, solvent and negative (water) controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.