1,1,3,3-tetramethyl-1,3-divinyldisiloxane

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:

1992-09-21 - 1992-11-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The restrictions are that the only positive control used with metabolic activation was 2-aminoanthracene.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

other: US EPA Standards 40 CFR 792 and 340 CFR 160

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

the only positive control used with metabolic activation was 2-aminoanthracene

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,1,3,3-tetramethyl-1,3-divinyldisiloxane

EC Number:

220-099-6

EC Name:

1,1,3,3-tetramethyl-1,3-divinyldisiloxane

Cas Number:

2627-95-4

Molecular formula:

C8H18OSi2

IUPAC Name:

ethenyl[(ethenyldimethylsilyl)oxy]dimethylsilane

Constituent 2

Reference substance name:

002627-95-4

Cas Number:

002627-95-4

IUPAC Name:

002627-95-4

Method

Target gene:

Histidine operon (Salmonella) tryptophan operon (E. coli)

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:

S. typhimurium TA 1538

Species / strain 3

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

100, 333, 1000, 3333 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: the test article formed a solution in acetone

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene, all TA strains at 1.0 µg/plate, WP2 uvrA at 10 µg/plate

Remarks:

TA98, TA100, TA1535, TA1537, TA1538, WP2 uvrA with metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA98 without metabolic activation 1.0 µg/plate

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA1535 without metabolic activation 1.0 µg/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 without metabolic activation 75 µg/plate

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA1538 without metabolic activation 1.0 µg/plate

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

WP2 uvrA without metabolic activation 1000 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

ACTIVATION: S9 mix contained 10% S9 and glucose-6-phosphate and NADP as co-factors. 500 µl of S9 mix was added to 2 ml top agar giving a final concentration of approximately 2% S9.

DURATION

- Exposure duration: 48 hours at 37+/- 2ºC

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: triplicate plates, experiment repeated

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


OTHER:

Evaluation criteria:

For the test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article. Data sets for strains TA1535, TA1537 and TA 1538 will be judged positive if the increase in mean revertants is equal to or greater than three times the mean vehicle control value. Data sets for strains TA98, TA100 and WP2 uvrA will be judged positive if the increase in mean revertants is equal to or greater than two times the mean vehicle control value.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

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

Remarks:

Precipitate but no appreciable toxicity was observed

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

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

Remarks:

Precipitate but no appreciable toxicity was observed

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS

- Precipitation: occurred between 1000 and 5000 µg/plate, did not interfere with test.

RANGE-FINDING/SCREENING STUDIES:

COMPARISON WITH HISTORICAL CONTROL DATA: yes

ADDITIONAL INFORMATION ON CYTOTOXICITY: cytotoxicity was not evident at any concentration

Any other information on results incl. tables

Summary of results – Experiment I Revertants per plate (mean of 3 plates)

 

Dose µg/ml	+/- metabolic activation	Average revertants per plate
		TA98	TA100	TA1535	TA1537	TA1538	WP2 uvrA
Solvent control	-	14	161	10	4	6	19
100	-	17	151	7	5	7	14
333	-	14	158	11	4	8	14
1000	-	15	164	10	4	8	13
3333	-	16	162	9	3	9	16
5000	-	16	158	8	6	6	15
Positive control	-	195	707	355	224	279	150
Solvent control	+	28	177	11	8	11	20
100	+	24	189	11	7	8	19
333	+	20	185	14	5	11	18
1000	+	21	186	8	8	14	18
3333	+	22	184	12	5	12	16
5000	+	26	174	10	7	13	11
Positive control	+	1948	1269	37	39	228	374

 

Summary of results – Experiment II

 

 

Dose µg/ml	+/- metabolic activation	Average revertants per plate
		TA98	TA100	TA1535	TA1537	TA1538	WP2 uvrA
Solvent control	-	11	123	6	5	7	15
100	-	12	111	11	4	7	15
333	-	8	113	5	4	5	12
1000	-	14	120	7	4	6	10
3333	-	9	121	10	4	5	15
5000	-	15	151	12	5	8	10
Positive control	-	123	386	297	301	295	145
Solvent control	+	19	137	14	4	13	20
100	+	18	139	12	7	10	15
333	+	19	144	7	6	14	19
1000	+	23	139	11	6	14	14
3333	+	20	143	10	6	7	10
5000	+	22	150	13	9	14	15
Positive control	+	817	814	51	95	818	410

 

Applicant's summary and conclusion

Conclusions:

1,1,3,3-Tetramethyl-1,3-divinyldisiloxane has been tested for mutagenicity to bacteria in a reliable study which was conducted according to a protocol that is equivalent to OECD TG 471, and in compliance with GLP. No evidence of a test-substance related increase in the number of revertants was observed with or without metabolic activation in the initial or the repeat experiments using Salmonella typhimurium strains TA 98, 100, 1535, 1537 and 1538, and E.coli WP2uvrA. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.