Trimethoxy(methyl)silane

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:

2003-10-09 to 2003-12-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1998

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Testing Guidelines of the ICH, S2A and S2B documents for Genotoxicity Testing of Pharmaceuticals, 1996 and 1997

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxy(methyl)silane

EC Number:

214-685-0

EC Name:

Trimethoxy(methyl)silane

Cas Number:

1185-55-3

Molecular formula:

C4H12O3Si

IUPAC Name:

trimethoxy(methyl)silane

Test material form:

liquid

Method

Species / strain

Species / strain / cell type:

bacteria, other: Salmonella typhimurium: TA-1535, TA-1537, TA-98 and TA-100; Escherichia coli: WP2 uvrA

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: DMSO
- Justification for choice of solvent/vehicle: none given in report

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

Remarks:

all strains 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:

TA 98 without metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100, TA 1535 without metabolic activation

Controls 4

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 metabolic activation

Controls 5

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

Details on test system and experimental conditions:

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

DURATION
- Preincubation period: 60 minutes
- Exposure duration: 48-72 hours
- Expression time (cells in growth medium): 48-72 hours

NUMBER OF REPLICATIONS: plated in triplicate; initial assay had an unacceptable vehicle control value, so the experiment was repeated with preincubation

DETERMINATION OF CYTOTOXICITY
- Method: other: reduction in mean number of revertants; condition of background lawn

Evaluation criteria:

Responses (number of revertants) to the test article were compared to concurrent negative and positive controls. A dose-related increase in at least one strain over a minimum of two increasing concentrations. Increase must be greater than or equal 3.0 times control for strains TA 1535 an dTA 1537, or 2.0 times for all other strains.

Statistics:

No statistical evaluation required.

Results and discussion

Test results

Key result

Species / strain:

bacteria, other: Salmonella typhimurium: TA-1535, TA-1537, TA-98 and TA-100; |Escherichia coli: WP2 uvrA

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:

Neither precipitate nor appreciable toxicity was observed.
All strains were tested in a preliminary toxiicty assay, with and without metabolic activation. No toxicity was observed.

Any other information on results incl. tables

Table 1 Experiment B1/B2: Plate incorporation - number of revertants per plate (mean of three plates)

Concentration  µg/plate	TA98		TA100		TA1535		TA1537		WP2
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0	11	23	125	210	13	10	8	9	12	10
100	11	23	116	210	14	9	9	11	14	13
333	11	23	138	202	13	9	9	7	11	9
1000	11	21	147	180	13	10	7	7	8	11
3333	12	25	130	213	11	10	7	9	11	12
5000	11	20	134	211	16	10	8	10	10	9
Positive	64	391	454	1108	366	121	407	101	117	477

Table 2 Experiment B4: Plate incorporation, repeat with dried vehicle - number of revertants per plate (mean of three plates)

Concentration  µg/plate	TA98		TA 100
	- MA	+ MA	- MA
0	17	34	184
100	15	28	155
333	16	33	178
1000	18	32	179
3333	19	40	191
5000	15	32	184
Positive	196	1422	568

Table 3 Experiment B3: Preincubation - number of revertants per plate (mean of three plates)

Concentration µg/plate	TA98		TA100		TA1535		TA1537		WP2
	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA	- MA	+ MA
0	14	22	130	223	16	13	3	9	14	16
100	13	21	146	230	14	11	4	9	11	17
333	12	21	122	198	14	16	6	7	11	15
1000	15	22	129	232	21	12	4	6	12	12
3333	13	26	139	239	16	14	2	7	13	13
5000	18	23	154	246	15	12	4	7	14	13
Positive	441	578	463	702	277	69	262	79	331	116

Applicant's summary and conclusion

Conclusions:

Methyltrimethoxysilane has been tested according to OECD 471 and under GLP. No increase in the frequency of revertants relative to control was observed with or without activation at any concentration, in any of the test organisms. The findings of the initial plate incorporation assay were confirmed in the repeat pre-incubation assay. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.