Triethoxy(vinyl)silane

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:

15 Aug 2001 to 01 Mar 2002

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

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Triethoxy(vinyl)silane

EC Number:

201-081-7

EC Name:

Triethoxy(vinyl)silane

Cas Number:

78-08-0

Molecular formula:

C8H18O3Si

IUPAC Name:

triethoxy(vinyl)silane

Method

Target gene:

his operon (for S. typhimurium strains) and trp operon (for E. coli strain)

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 uvr A

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254

Test concentrations with justification for top dose:

Preliminary toxicity study: 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500, and 5000 µg/plate
Mutagenicity test, main study (with and without activation): 50, 150, 500, 1500, and 5000 µg/plate

Vehicle / solvent:

- Vehicle/solvent used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: 2-aminoanthracene (2-AA; +S9, 1 µg/plate for TA 100; 2 µg/plate for TA 1535, TA 1537; 10 µg/plate for WP2 uvrA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 3 plates per experiment, 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: growth of background lawn

Evaluation criteria:

The spontaneous reversion for the solvent control should be within historical control data. The positive controls should demonstrate that the test systems are responsive to known mutagens (induction of at least twice the respective vehicle control).
Positive reaction:
- number of revertants is statistically significantly increased compared to the solvent control in at least one strain
- the increase is reproducible and there is evidence of a dose-response relationship

Statistics:

Dunnett´s method of linear regression (for assessment of dose-response relationship)

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

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:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

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:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

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:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium 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:

not applicable

Positive controls validity:

valid

Test results 5

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:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: No toxicity was observed in the preliminary toxicity test in TA 100 and WP2 uvrA with and without metabolic activation up to the maximum concentration of 5000 µg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA: negative control data were within historical control values

Precipitates: No test material precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix.

Any other information on results incl. tables

Table 1: Results of the first experiment with and without metabolic activation.

With or without S9-Mix	Test substance concentration (µg/plate)	Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation)
		TA 98	TA100	TA1535	TA1537	WP2 uvrA
–	0	23±5	77±7	13±1	7±2	20±1
–	50	15±1	81±7	12±6	6±5	17±4
–	150	16±2	87±2	12±6	9±2	19±6
–	500	14±3	85±10	14±1	8±1	13±3
–	1500	21±3	88±15	12±3	12±3	18±4
–	5000	24±5	88±5	17±4	8±2	18±6
Positive controls, –S9	Name	4-NQO	ENNG	ENNG	9-AA	ENNG
	Concentrations (µg/plate)	0.2	3	5	80	2
	Revertants per plate	91±9	439±29	221±22	2741±121	356±28
+	0	25±1	82±12	10±2	9±2	23±3
+	50	24±5	85±9	10±4	13±6	18±4
+	150	26±4	81±3	11±5	13±1	26±9
+	500	22±7	77±9	12±2	13±3	20±1
+	1500	23±2	88±8	10±3	11±4	19±3
+	5000	24±7	91±10	11±3	11±5	24±6
Positive controls, +S9	Name	BP	2-AA	2-AA	2-AA	2-AA
	Concentrations (µg/plate)	5	1	2	2	10
	Revertants per plate	206±12	825±65	235±7	284±11	801±20

Table 2: Results of the second experiment with and without metabolic activation.

With or without S9-Mix	Test substance concentration (µg/plate)	Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation)
		TA 98	TA100	TA1535	TA1537	WP2 uvrA
–	0	17±3	95±12	15±6	9±6	19±5
–	50	22±2	109±10	13±5	7±4	19±4
–	150	15±4	88±6	18±6	9±4	18±3
–	500	23±5	95±2	14±3	9±1	18±2
–	1500	20±8	104±3	23±5	8±1	22±5
–	5000	24±9	104±2	17±7	8±2	21±3
Positive controls, –S9	Name	4-NQO	ENNG	ENNG	9-AA	ENNG
	Concentrations (µg/plate)	0.2	3	5	80	2
	Revertants per plate	160±11	104±2	187±19	8±2	21±3
+	0	29±6	111±4	18±7	9±4	22±5
+	50	26±4	102±5	22±4	6±1	17±3
+	150	33±5	105±15	14±3	9±4	22±4
+	500	36±6	112±8	18±2	7±3	24±6
+	1500	25±8	103±7	20±6	7±1	19±4
+	5000	30±7	112±9	22±6	10±2	23±
Positive controls, +S9	Name	BP	2-AA	2-AA	2-AA	2-AA
	Concentrations (µg/plate)	5	1	2	2	10
	Revertants per plate	466±28	1152±67	408±28	536±26	909±177

4-NQO: 4-Nitroquinoline-1-oxide

ENNG: N-ethyl-N'-nitro-N-nitrosoguanidine

9-AA: 9-Aminoacridine

2 -AA: 2 -Aminoanthracene

BP: Benzo(a)pyrene

Applicant's summary and conclusion

Conclusions:

Under test conditions, no mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.