N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine

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:

2002-05-10 to 2002-09-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine

EC Number:

231-701-1

EC Name:

N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine

Cas Number:

7691-02-3

Molecular formula:

C8H19NSi2

IUPAC Name:

bis(ethenyldimethylsilyl)amine

Method

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:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Experiment 1: 100, 316, 1000, 3160, 5000 µg/plate; Experiment 2: 31.6, 100, 316, 1000, 3160 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethylene glycol dimethylether

- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535, TA 100 (without 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:

TA 98 (without activation)

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 (without activation)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

TA 102 (without activation)

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-anthracene amide

Remarks:

TA 98, TA 102, TA 1537 (with activation)

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

TA 100, TA 1535 (with activation)

Details on test system and experimental conditions:

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

DURATION
- Preincubation period: 60 minutes

- Expression time (cells in growth medium): 48 hours

NUMBER OF REPLICATIONS: 3 plates per concentration

DETERMINATION OF CYTOTOXICITY
- Method: condition of bacterial lawn and reduction in the number of revertants

METABOLIC ACTIVATION: The S9 mix contained 5% S9 from Aroclor 1254-induced rat liver, and NADP and glucose-9-phosphate as co-factors. 0.5 ml of S9 mix were added to top agar, bacterial suspension and test material (or solvent or positive control) to a final volume of 2.7 ml and a final S9 concentration of approximately 1%.

Evaluation criteria:

A result is considered positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.

Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar
plates.

Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn.

Statistics:

MANN and WHITNEY and Spearman’s rank.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

3160 and 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data

Any other information on results incl. tables

Table 2: Dose range-finding study Number of revertants per plate (2 plates)

	TA100
Conc. (µg/plate)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	141	156	No
0.316	173	121	No
1	159	138	No
3.16	146	139	No
10	154	192	No
31.6	150	129	No
100	122	132	No
316	116	161	No
1000	140	158	No
3160	166	163	No
5000	0	0	Yes

*solvent control with ethylene glycol dimethyl ether

Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA102
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	37.7	34.7	No	155.3	150.3	No	279.7	278	No
100	33.3	32	No	145	132.7	No	270	270.7	No
316	26	36	No	150.3	140	No	273.7	258.3	No
1000	27	36.3	No	152	140	No	273.7	259	No
3160	38.7	37	No	146.3	157.3	No	272	261	No
5000	0	0	Yes	0	0	Yes	0	0	Yes
Positive control	826	543	No	1039.3	1037.7	No	1064.7	1063.7	No

*solvent control with ethylene glycol dimethyl ether

Table 3: Experiment 1 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	13.7	13	No	4.3	5.7	No
100	14	15	No	4	3	No
316	13	13	No	3	5	No
1000	12.3	13.7	No	3	4.7	No
3160	13.7	12.7	No	4	4	No
5000	0	0	Yes	0	0	Yes
Positive control	468.3	477	No	481.7	484	No

*solvent control with ethylene glycol dimethyl ether

Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA102
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	31.3	51	No	136	153.7	No	280.3	284	No
31.6	32	30.3	No	156	163.7	No	265.3	274	No
100	35	32.3	No	159.7	174	No	263.3	267	No
316	32	39.7	No	161.3	163	No	280	275	No
1000	31	28	No	161	148.3	No	282.7	270.7	No
3160	0	28.3	Yes	0	155.3	Yes	0	0	Yes
Positive control	895	780	No	1011	1008.7	No	1365	1398.3	No

*solvent control with ethylene glycol dimethyl ether

Table 4: Experiment 2 Preincubation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	14	13.7	No	3.7	4.7	No
31.6	13.3	13	No	4.3	3.3	No
100	13	14	No	3.3	4.3	No
316	13.3	14	No	4.7	5	No
1000	14	12.3	No	3.7	4	No
3160	0	0	Yes	0	0	Yes
Positive control	487.3	468	No	470.7	475.7	No

*solvent control with ethylene glycol dimethyl ether

Applicant's summary and conclusion

Conclusions:

N-(dimethylvinylsilyl)-1,1-dimethyl-1-vinylsilylamine has been tested for mutagenicity to bacteria in a reliable study conducted according to OECD Test Guideline 471, and in compliance with GLP. No test-substance meditated increase in the number of revertants was observed when the substance was tested up to cytotoxic concentration in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 either with or without metabolic activation. The results were confirmed in a second independent experiment. Appropriate solvent and positive 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.