3-aminopropyltriethoxysilane

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:

1998-12-01 to 1998-12-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The restrictions were that only four strains of bacteria were used

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

yes

Remarks:

4 strains used

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-aminopropyltriethoxysilane

EC Number:

213-048-4

EC Name:

3-aminopropyltriethoxysilane

Cas Number:

919-30-2

Molecular formula:

C9H23NO3Si

IUPAC Name:

silane

Test material form:

liquid

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital and ß-Naphthoflavone induced rat liver S9

Test concentrations with justification for top dose:

0, 50, 160, 500, 1600 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:

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:

other: 2-aminoanthracene

Remarks:

All strains (with activation)

Details on test system and experimental conditions:

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

DURATION

- Preincubation period: 30 minutes

- Exposure duration: 72 hours

- 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

Evaluation criteria:

For a test compound to be considered positive, it must (in two independent experiments) cause at least a doubling in the mean revertants per plate of at least one tester strain. This increase must be accompanied by a dose response towards increasing concentrations of the test article. Single increases in revertant frequencies, which are not dose-related and not reproducible in two independent tests are considered non-relevant. If however these increases do occur in both tests, this will be taken as an indication of mutagenic effect.

Statistics:

Mean number of revertants per plate and the standard deviation around the mean were calculated.

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:

other: >5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: >5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: >5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

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:

other: >5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

COMPARISON WITH HISTORICAL CONTROL DATA: Numbers of spontaneous revertants were within acceptable range

Remarks on result:

other: No mutagenic potential

Any other information on results incl. tables

Table 2a: 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*	14	30	No	139	151	No	8	9	No
50	16	37	No	147	144	No	8	11	No
160	16	28	No	138	143	No	8	10	No
500	14	29	No	136	150	No	11	9	No
1600	22	41	No	136	150	No	9	13	No
5000	21	27	No	10	171	Yes	10	9	No
Positive Control	104.2	1490	No	536	1592	No	316	153	No

*solvent control with DMSO

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

	TA1537
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)
0*	5	13	No
50	0	11	No
160	2	15	No
500	2	10	No
1600	2	9	No
5000	0	3	Yes
Positive Control	84	109	No

*solvent control with DMSO

Table 3a: 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*	19	25	No	121	116	No	12	9	No
250	21	25	No	97	102	No	7	11	No
500	20	30	No	98	91	No	13	11	No
1000	17	32	No	100	99	No	11	15	No
2000	18	31	No	101	110	No	8	10	No
4000	16	30	No	100	103	No	9	14	No
Positive Control	103	1628	No	608	1384	No	341	216	No

*solvent control with DMSO

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

	TA1537
Conc. (µg/plate)	— MA	+ MA	Cytotoxic (yes/no)
0*	15	16	No
250	17	10	No
500	17	13	No
1000	17	15	No
2000	13	15	No
4000	12	13	No
Positive Control	263	131	No

*solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

3-aminopropyl(triethoxy)silane has been tested in a reliable study according to OECD TG 471 and in compliance with GLP using Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537. The test substance did not show any reproducible mutagenic activity in any of the strains tested up to limit concentrations with and without metabolic activation in either the plate incorporation or the repeat preincubation assay. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.