Methylsilanetriyl triacetate

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:

2001-10-24 - 2001-11-28

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)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methylsilanetriyl triacetate

EC Number:

224-221-9

EC Name:

Methylsilanetriyl triacetate

Cas Number:

4253-34-3

Molecular formula:

C7H12O6Si

IUPAC Name:

methylsilanetriyl triacetate

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 1254 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: DMSO
- Justification for choice of solvent/vehicle: Sponsor's request due to compatibility with the target cells. A fresh bottle, containing less that 0.1% water, to be opened and used once for each phase of the study.

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 10 µg/plate

Remarks:

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:

other: 2-aminoanthracene 1.0 µg/plate

Remarks:

TA98, TA100, TA1535, TA1537 with metabolic activation

Controls 3

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 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100, TA1535 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:

9-aminoacridine

Remarks:

TA1537 without metabolic activation 75 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 glucose-6 phosphate and NADP as co-factors, and 10% S9. 0.5 ml of S9 was added to 2 ml top agar, 100 µl tester strain and 50 µl of test solution giving a final concentration of 1% S9.

DURATION

- Exposure duration: 48 - 72 hours at 37±2°C


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:

The mean of each positive control must exhibit at least a 3 fold increase in the number of revertants over the mean value of the respective vehicle control. A minimum of three non-toxic dose levels is required to evaluate assay data. A dose level is considered toxic if one or both of the following criteria are met: (1) A >50% reduction in the mean number of revertants per plate as compared to the mean vehicle control value. This reduction must be accompanied by an abrupt dose-dependent drop in the revertant count. (2) A reduction in the background lawn. Data sets will be judged positive if the increase in mean revertants at the peak dose response is equal to or greater than 2 times the mean negative control value.

Statistics:

None shown in report

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:

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

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

 Experiment 1 Plate incorporation - Number of revertants per plate (mean of three plates)

Treatment µg/plate	TA98		TA100		TA1535		TA1537		WP2 uvrA
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
0*	15	18	154	181	14	12	4	7	11	11
100	11	21	170	161	13	10	3	5	10	8
333	11	16	155	196	9	13	4	6	9	6
1000	11	17	140	178	13	11	3	5	9	8
3333	15	18	166	152	21	8	6	4	10	12
5000	20	21	149	159	20	14	5	5	10	8
Positive control	92	365	479	584	215	102	633	58	71	296

*solvent control with DMSO

 Experiment 2 Plate incorporation - Number of revertants per plate (mean of three plates)

Treatment µg/plate	TA98		TA100		TA1535		TA1537		WP2 uvrA
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
0 *	16	20	134	154	19	12	8	7	12	12
100	10	19	138	165	21	15	5	10	14	13
333	15	23	152	163	17	19	5	10	12	17
1000	15	28	137	181	19	14	13	9	12	16
3333	15	25	136	145	21	16	9	6	10	14
5000	13	22	124	151	18	16	7	4	10	13
Positive control	67	495	441	690	203	124	352	137	84	291

 *solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

Methylsilanetriyl triacetate has been tested for mutagenicity to bacteria in a study which was conducted according to the 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. Appropriate positive 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.