3,3-bis[(dimethylvinylsilyl)oxy]-1,1,5,5-tetramethyl-1,5-divinyltrisiloxane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25.08.2011 - 15.09.2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Version / remarks:

Kanpoan No.287

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3,3-bis[(dimethylvinylsilyl)oxy]-1,1,5,5-tetramethyl-1,5-divinyltrisiloxane

EC Number:

262-061-1

EC Name:

3,3-bis[(dimethylvinylsilyl)oxy]-1,1,5,5-tetramethyl-1,5-divinyltrisiloxane

Cas Number:

60111-54-8

Molecular formula:

C16H36O4Si5

IUPAC Name:

tetraethenyldimethylsilyl silicate

Constituent 2

Reference substance name:

060111-54-8

Cas Number:

060111-54-8

IUPAC Name:

060111-54-8

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbitol/beta-naphthoflavone induced rat liver S9

Test concentrations with justification for top dose:

3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: the solvent was requested by the sponsor.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Acetone

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535, TA100 without metabolic activation 10 µg/plate

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Acetone

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylene-diamine 10 µg/plate TA98 and 50 µg/plate TA1537

Remarks:

TA1537, TA98 without metabolic activation

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Acetone

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2 uvrA without metabolic activation 3 µl/plate

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Acetone

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene 2.5 µg/plate TA1535, TA1537, TA98, TA100 and 10 µg/plate WP2 uvrA

Remarks:

TA1535, TA1537, TA98, TA100, WP2 uvrA with metabolic activation

Details on test system and experimental conditions:

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

ACTIVATION: S9 mix contained glucose-6-phosphate and NADP as co-factors. The amount of S9 supernatant was 10% v/v in the S9 mix. 0.5 ml S9 was added to test solution, bacterial suspension and top agar giving a final concentration in the cultures of approximately 2% S9.

DURATION
- Preincubation period: 60 minutes at 37C
- Exposure duration: 72 hours

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: triplicate plates, pre-experiment for toxicity and experiment 1 used plate incorporation, the test was repeated using pre-incubation.

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn

Evaluation criteria:

A test item is considered as a mutagen if a biologically relevant increase in the mean number of revertant colonies exceeding the threshold of twice (strains TA98, TA100 and WP2 uvrA) or thrice (strains TA1535 and TA1537) the mean colony count of the corresponding solvent control is observed. A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration. An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.

Statistics:

No statistical evaluation of the data was required.

Results and discussion

Test results

Test results 1

Key result

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 nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

E. coli WP2 uvr A

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

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS

- Precipitation: No precipitation was observed


ADDITIONAL INFORMATION ON CYTOTOXICITY: Cytotoxicity was not evident at any concentrations

Any other information on results incl. tables

Table 1: Experiment 1 - Mean revertant colony counts

	TA 1535		TA 1537		TA 98		TA 100		WP2 uvrA
Concentration (µg/plate)	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Solvent control	14	21	15	25	33	38	126	130	47	49
Negative control	16	17	17	21	37	54	120	127	44	49
3	12	21	16	24	32	41	123	120	52	49
10	13	18	14	24	34	37	117	131	40	56
33	15	21	18	21	36	37	129	105	44	49
100	13	24	16	24	39	39	139	131	40	53
333	15	18	18	19	38	29	134	134	47	48
1000	14	16	16	15	38	23	142	135	51	46
2500	18	17	18	16	38	23	127	124	45	44
5000	14	18	17	15	29	18	129	119	39	31
Positive control	1536	313	71	388	326	1266	1791	2270	956	227

 

  Table 2: Experiment 2 Mean revertant colony counts 

 

	TA 1535		TA 1537		TA 98		TA 100		WP2 uvrA
Concentration (µg/plate)	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Solvent control	16	21	22	26	37	37	132	139	49	63
Negative control	18	16	24	28	41	45	142	143	52	64
3	NA	19	NA	26	NA	41	NA	159	NA	58
10	NA	21	NA	24	NA	39	NA	162	NA	55
33	18	24	21	26	31	44	124	124	50	61
100	16	21	24	30	33	40	140	161	58	53
333	17	18	24	19	37	35	134	150	51	53
1000	17	15	21	19	33	29	155	145	58	58
2500	15	16	20	17	30	31	156	127	56	37
5000	17	16	24	16	38	29	155	114	57	42
Positive control	1780	318	118	266	329	1655	1782	1602	643	261

Applicant's summary and conclusion

Conclusions:

3,3-Bis[(dimethylvinylsilyl)oxy]-1,1,5,5-tetramethyl-1,5-divinyltrisiloxane has been tested for mutagenicity to bacteria, in a study which was conducted according to OECD Test Guideline 471 and in compliance with GLP. No evidence of a test substance related increase in the number of revertant colonies was observed with or without metabolic activation in the pre-experiment for toxicity or the initial assay using the plate incorporation method using S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2. The result was confirmed the repeat preincubation experiment. Appropriate positive, negative and solvent 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.