Triethoxypropylsilane

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:

1996-01-31 to 1996-02-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxypropylsilane

EC Number:

213-926-7

EC Name:

Trimethoxypropylsilane

Cas Number:

1067-25-0

Molecular formula:

C6 H16 O3 Si

IUPAC Name:

trimethoxy(propyl)silane

Method

Target gene:

his operon

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

other: rfa, uvrB (TA 98 and 100: pKM101)

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:

50 - 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

- Justification for choice of solvent/vehicle: It is assumed by the reviewer that the solvent was chosen for its solubility properties and relative non-toxicity to bacteria.

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:

+ S9: All strains: 2.5µg/plate in DMSO

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

-S9: TA 98: 2.5 µg/plate in DMSO

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

-S9: TA 100 and TA 1535: 5.0 and 2.5 µg/plate in aqua bidest, respectively.

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

- S9: TA 1537: 25 µg/plate in DMSO

Details on test system and experimental conditions:

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

DURATION

- Preincubation period: 30 minutes

- Expression time (cells in growth medium): 72 hours

NUMBER OF REPLICATIONS: 3 Plates per test concentration

DETERMINATION OF CYTOTOXICITY

- Method: relative total growth, background lawn assessment


METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

OTHER: S9 mix was prepared freshly before use. One part of S9 fraction was mixed with 9 parts of a cofactor solution resulting in the following mixture:
-10% S9 fraction
- 33 mM KCl
- 8 mM MgCl2
- 5 mM glucose-6-phosphate
- 4 mM NADP
- 100 mM Na2HPO4/NaH2PO4, pH 7.4.

Evaluation criteria:

For a test substance to be considered positive, it must cause at least a doubling in the mean revertants per plate of at least one tester strain with a minimum of two increasing concentrations of test article.
The increase must be accompanied by a dose response towards increasing concentrations of the test article.

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:

cytotoxicity

Remarks:

5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

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:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

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:

cytotoxicity

Remarks:

5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

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*	21	42	No	91	109	No	8	11	No
50	24	46	No	141	121	No	16	11	No
160	20	45	No	134	131	No	8	10	No
500	25	36	No	113	134	No	7	16	No
1600	25	39	No	130	135	No	9	11	No
5000	30	31	No	137	115	No	9	15	No
Positive Control	142	1324	No	544	1474	No	322	195	No

*solvent control with DMSO

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

	TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)
0*	2	23.4	No
50	6	14	No
160	8	16	No
500	9	9	No
1600	6	13	No
5000	2	16	No
Positive Control	3	152	No

*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*	23	35	No	147	119	No	9	11	No
50	19	38	No	108	111	No	6	13	No
160	20	29	No	110	137	No	6	13	No
500	18	25	No	104	137	No	6	11	No
1600	21	32	No	123	148	No	6	13	No
5000	6	12	Yes	48	76	Yes	0	1	Yes
Positive Control	110	1264	No	527	1466	No	306	220	No

*solvent control with DMSO

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

	TA1537
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)
0*	5	15	No
50	6	10	No
160	5	11	No
500	5	9	No
1600	3	12	No
5000	0	5	Yes
Positive Control	100	164	No

*solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
negative with and without metabolic activation

Under test conditions, no mutagenic effect was observed for trimethoxy(propyl)silane (CAS: 1067-25-0) without and with metabolic activation.