3-(triethoxysilyl)propanethiol

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:

2000/10/02 - 2001/02/12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-(triethoxysilyl)propanethiol

EC Number:

238-883-1

EC Name:

3-(triethoxysilyl)propanethiol

Cas Number:

14814-09-6

Molecular formula:

C9H22O3SSi

IUPAC Name:

3-(triethoxysilyl)propane-1-thiol

Constituent 2

Reference substance name:

014814-09-6

Cas Number:

014814-09-6

IUPAC Name:

014814-09-6

Test material form:

liquid

Method

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:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

Without metabolic activation: 50, 150, 500, 1500 and 5000 µg/plate; with metabolic activation - 5.0, 15, 50, 150, 500, 1500 and 5000 µg/plate.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: Based on the sponsor's request due to compatibility with the target cells and solubility of the test article

Controls

Controls 1

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 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene 1.0 µg/plate and 10 µg/plate

Remarks:

TA98, TA100, TA1535, TA1537 - 1.0 µg/plate and WP2 uvrA - 10 µg/plate all with metabolic activation

Controls 3

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

Controls 4

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 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100 and TA1535 without metabolic activation 1.0 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION:
- In agar (plate incorporation); preincubation

ACTIVATION:
- S9 mix contained 10% S9, glucose-6-phosphate and NADP as co-factors. 0.5 mL S9 mix, 100 µL of tester strain and 25 µL of vehicle or test article were added to 2 mL top agar, giving a final concentration of approximately 2% S9.

DURATION
- Preincubation period: 60+/-2 minutes at 37ºC
- Exposure duration: 48- 72 hours at 37ºC+/-2ºC

SELECTION AGENT (mutation assays):
- Histidine deficient agar

NUMBER OF REPLICATIONS:
- Triplicate plates, experiment repeated

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

Evaluation criteria:

A result is positive if the increase in mean revertants at the peak of the dose response in strains TA1535 and TA1537 is equal to or greater than three times the mean negative control value. In strains TA 98, TA 100 and E. coli WP2 uvrA, the result is considered positive if the increase in mean revertants at the peak of the dose response is equal to or greater than two times the mean negative control value.

Statistics:

None stated in report

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxicity toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxicity toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.

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:

cytotoxicity

Remarks:

cytotoxicity toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.

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:

cytotoxicity

Remarks:

toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA:
- Yes

Any other information on results incl. tables

Summary of results – Experiment B1

Dose µg/ml	+/- metabolic activation	Average revertants per plate (mean of 3 plates)
		TA98	TA100	TA1535	TA1537	WP2 uvrA
Solvent control	-	14	90	13	5	13
50	-	15	83	11	6	14
150	-	14	74	11	5	11
500	-	13	53	12	5	11
1500	-	12	36	7	4	10
5000	-	9	14	8	3	6
Positive control	-	282	557	595	1490	90
Solvent control	+	23	94	15	7	13
5.0	+	16	94	13	8	n.t.
15	+	15	101	16	7	n.t.
50	+	16	84	12	7	13
150	+	14	93	8	5	14
500	+	11	11	8	4	11
1500	+	2	10	6	2	14
5000	+	n.t	n.t.	n.t.	n.t.	10
Positive control	+	773	941	171	161	66

Repeated assay due to excessive toxicity in Experiment B1

Dose µg/ml	+/- metabolic activation	Average revertants per plate
		TA100	TA1537
Solvent control	-	108	6
15	-	n.t.	8
50	-	84	11
150	­-	85	6
500	­-	93	6
1500	-	83	7
5000	-	83	6
Positive control	-	407	763

Independent repeat assay

Dose µg/ml	+/- metabolic activation	Average revertants per plate
		TA98	TA100	TA1535	TA1537	WP2 uvrA
Solvent control	-	12	86	9	5	12
5.0	-	n.t	n.t	n.t	n.t	14
15	-	10	95	13	6	11
50	-	13	98	11	5	12
150	-	13	99	11	5	11
500	-	13	113	12	5	12
1500	-	11	70	11	7	15
5000	-	8	63	15	7	n.t
Positive control	-	92	359	274	752	209
Solvent control	+	26	120	13	7	12
5.0	+	19	116	12	4	n.t.
15	+	22	105	13	7	10
50	+	26	80	16	5	13
150	+	26	109	11	6	11
500	+	18	97	13	3	14
1500	+	5	66	11	5	13
5000	+	n.t	n.t.	n.t.	n.t.	12
Positive control	+	509	1129	100	118	290

Repeat assay due to unacceptable vehicle control in independent repeat assay

Dose µg/ml	+/- metabolic activation	Average revertants per plate
		WP2 uvrA
Solvent control	-	18
50	-	17
150	­-	16
500	­-	16
1500	-	20
5000	-	19
Positive control	-	597

Applicant's summary and conclusion

Conclusions:

3-(triethoxysilyl)propanethiol has been tested for mutagenicity to bacteria in a study conducted according to OECD Test Guideline 471 and in compliance with GLP (reliability score 1). No evidence of a test substance related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.