Trimethoxysilane

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxysilane

EC Number:

219-637-2

EC Name:

Trimethoxysilane

Cas Number:

2487-90-3

Molecular formula:

C3H10O3Si

IUPAC Name:

Trimethoxysilane

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9 homogenate 

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: the solvent was chosen based on solubility of the test article and compatibility with the target cells.

Controls

Controls 1

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 2

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 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:

WP2, WP2uvrA (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-Aminoanthracene

Remarks:

All strains (with activation)

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sterigmatocystin

Remarks:

All strains (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 to 72 hours

NUMBER OF REPLICATIONS: 2 plates per test concentration

DETERMINATION OF CYTOTOXICITY

- Method: relative total growth; background lawn assessment

Evaluation criteria:

The test article is evaluated as positive when it causes a dose-related increase in mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article.

Statistics:

Positive controls and tester strains with revertant counts greater than 100 were counted with a colony counter (Mini Count) and those less than 100 were counted manually.

Results and discussion

Test results

Test results 1

Key result

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

Remarks:

> 5000 µg/plate

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

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

Remarks:

> 5000 µg/plate

Vehicle controls validity:

valid

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:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

> 5000 µg/plate

Vehicle controls validity:

valid

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:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

> 5000 µg/plate

Vehicle controls validity:

valid

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

Remarks:

> 5000 µg/plate

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

E. coli WP2

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

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none recorded
- Effects of osmolality: none recorded
- Evaporation from medium: not reported
- Precipitation: Slight precipitation at higher concentrations did not affect assay
- Other confounding effect: In first two tests, a variation in the precipitation pattern was observed, so the tests were repeated. The findings from the initial two experiments are not recorded.

RANGE-FINDING/SCREENING STUDIES:
No toxicity observed

COMPARISON WITH HISTORICAL CONTROL DATA:
The results of the controls lie within the range of the historical control data.


ADDITIONAL INFORMATION ON CYTOTOXICITY: None

Remarks on result:

other: all strains/cell types tested

Any other information on results incl. tables

 Table 1 Preliminary toxicity test

	TA 100			WP2 uvrA (pKM101)
Concentration (µg/Plate)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)
0	199	174	no	250	208	no
6.7	180	173	no	234	187	no
10	165	157	no	241	210	no
33	174	163	no	200	198	no
67	179	197	no	228	185	no
100	196	152	no	195	217	no
333	177	170	no	186	184	no
667	175	175	no SP	230	214	no SP
1000	169	156	no SP	138	168	no SP
3333	199	174	no SP	221	169	no SP
5000	174	158	no SP	247	180	no SP

SP Slight precipitate

 

Table 2: Experiment 1 Plate incorporation assay [Number of revertants per plate (mean of 3 plates)]

	TA98			TA100			TA1535
Conc. (µg/plate)	-MA	+ MA	Cytotoxic (yes/no)	-  MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
0*	13	17	no	95	144	no	10	11	no
100	13	17	no	89	127	no	9	11	no
333	13	18	no	86	135	no	8	11	no
1000	14	16	no	85	116	no	9	11	no
3333	17	21	no	97	116	no	6	14	no
5000	13	21	no	95	111	no	7	13	no
Positive Control	1304	1050	-	581	997	-	497	124	-

*solvent control with DMSO

 

Table 2: Experiment 1 Plate incorporation assay [Number of revertants per plate (mean of 3 plates)]

	TA1537			WP2 uvrA (pKM101)			WP2 (pKM101)
Conc. (µg/plate)	-MA	+ MA	Cytotoxic (yes/no)	-  MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
0*	4	6	no	226	263	no	65	64	no
100	4	10	no	236	295	no	54	64	no
333	3	5	no	239	258	no	87	60	no
1000	6	8	no	210	294	no	62	53	no
3333	5	8	no	213	273	no	67	64	no
5000	5	6	no	197	247	no	67	61	no
Positive Control	215	130	-	1554	1262	-	1476	499	-

 

 *solvent control with DMSO

 

Table 3: Experiment 2 Pre incubation assay [Number of revertants per plate (mean of 3 plates)]

	TA98			TA100			TA1535
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)	—  MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	15	24	no	102	129	no	11	10	no
50	26	24	no	112	122	no	10	11	no
160	21	20	no	105	116	no	11	9	no
500	24	14	no	101	120	no	12	10	no
1600	23	17	no	110	128	no	9	12	no
5000	19	18	no	100	123	no	10	11	no
Positive Control	764	909	-	527	902	-	433	117	-

*solvent control with DMSO

 

Table 3: Experiment 2 Pre incubation assay [Number of revertants per plate (mean of 3 plates)]

	TA1537			WP2 uvrA (pKM101)			WP2 (pKM101)
Conc. (µg/plate)	-MA	+ MA	Cytotoxic (yes/no)	-  MA	+ MA	Cytotoxic (yes/no)	- MA	+ MA	Cytotoxic (yes/no)
0*	5	7	no	204	334	no	23	21	no
100	5	5	no	274	278	no	25	21	no
333	5	5	no	173	316	no	26	25	no
1000	5	6	no	208	296	no	26	22	no
3333	5	4	no	206	285	no	31	28	no
5000	5	6	no	214	283	no	28	24	no
Positive Control	250	119	-	2225	1304	-	358	1222	-

 

*solvent control with DMSO

 

Applicant's summary and conclusion

Conclusions:

Trimethoxysilane has been tested according to OECD Test Guideline 471 and in compliance with GLP. No increase in the number of revertants was observed with or without metabolic activation in either the initial or the repeat assay using Salmonella typhimurium strains and E. coli WP2 uvrA, using the preincubation method. 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 this study.