3-(trimethoxysilyl)propylamine

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

Study period:

1997-08-07 to 1997-09-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Properties of test substance not determined by testing laboratory

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-(trimethoxysilyl)propylamine

EC Number:

237-511-5

EC Name:

3-(trimethoxysilyl)propylamine

Cas Number:

13822-56-5

Molecular formula:

C6H17NO3Si

IUPAC Name:

3-(trimethoxysilyl)propylamine

Test material form:

liquid

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 induced rat liver S9

Test concentrations with justification for top dose:

75-5000 µg/plate (Test 1); 33-5000 µg/plate (Test 2)

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: 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:

All Strains (with 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 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 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 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 activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 60 minutes

- Expression time (cells in growth medium): 48 - 72 hours

- Fixation time (start of exposure up to fixation or harvest of cells): 12 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

All Salmonella tester strain cultures must demonstrate the presence of the deep rough mutation and the deletion of the uvrB gene.

Cultures of tester strains TA 98 and TA 100 must demonstrate the presence of the pKM101 plasmid R-factor.

All WP2uvrA cultures must demonstrate the deletion in the uvrA gene.

Results must be within range of historical data: TA 98 10-50, TA 100 80-240, TA 1535 5-45, TA 1537 3-21, WP2uvrA 10-60.

A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and WP2uvrA and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.

Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar
plates.

Cytotoxicity is defined as a reduction in the mean number of revertants per plate by >50% compared with the mean vehicle control. The reduction
must be accompanied by an abrupt dose-dependant drop in the revertant count, and/or a reduction in background lawn.

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:

600 - 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate, without activation

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

600 - 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

600 - 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

600 - 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: Results were within range of historical control data

Any other information on results incl. tables

Table 2: Dose range-finding study, Number of revertants per plate (2 plates per strain)

	TA 100			WP2 uvrA
Concentration (µg/Plate)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)	Plate 1 + MA	Plate 2 - MA	Cytotoxic (Yes/No)
0	130	95	No	17	9	No
6.7	137	102	No	8	15	No
10	120	105	No	15	14	No
33	135	100	No	16	7	No
67	102	91	No	15	15	No
100	114	105	No	31	12	No
333	138	103	No	13	19	No
667	135	89	No	17	18	No
1000	95	98	No	15	16	No
3333	60	89	No	11	15	No
5000	59	66	No	11	9	Yes

*solvent control with DMSO

Table 3: Experiment 1 Mutagenicity 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	16	No	112	125	No	10	12	No
75	16	18	No	129	119	No	8	8	No
200	16	18	No	100	140	No	9	7	No
600	13	17	No	109	118	No	6	9	No
1800	7	15	No	8	70	Yes	3	10	Yes
5000	0	17	Yes	0	61	Yes	0	10	Yes
Positive control	553	1377	No	528	1103	No	397	100	No

*solvent control with DMSO

Table 4: Experiment 1 Mutagenicity Assay, Number of revertants per plate (mean of 3 plates)

	TA1537			WP2uvrA
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	5	7	No	13	15	No
75	3	5	No	15	14	No
200	4	4	No	15	15	No
600	1	4	Yes	14	17	No
1800	1	1	Yes	11	14	No
5000	0	2	Yes	1	15	Yes
Positive control	860	141	No	389	407	No

*solvent control with DMSO

Table 5: Experiment 2 Mutagenicity 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*	12	18	No	131	140	No	9	11	No
33	13	17	No	112	134	No	9	11	No
100	13	13	No	98	124	No	7	9	No
333	12	13	No	123	117	No	8	9	No
1000	12	17	No	104	105	No	6	7	No
5000	10	7	Yes	30	67	Yes	1	4	Yes
Positive control	749	1149	No	645	986	No	482	94	No

*solvent control with DMSO

Table 6: Experiment 2 Mutagenicity Assay, Number of revertants per plate (mean of 3 plates)

	TA1537			WP2 uvrA
Conc. µg/plate	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	5	8	No	13	14	No
33	5	4	No	13	11	No
100	5	4	No	13	11	No
333	5	5	No	11	10	No
1000	3	3	Yes	13	9	No
5000	1	1	Yes	5	12	Yes
Positive control	638	110	No	402	248	No

*solvent control with DMSO

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative with and without metabolic activation

3-(trimethoxysilyl)propylamine has been tested in a valid and reliable study according to OECD 471 and under GLP. No mutagenic effect was observed for the test substance tested up to limit concentration in any of the test strains with and without metabolic activation in Salmonella typhimurium strains TA 98, 100, 1535, 1537 and E.coli WP2 uvrA. The result of the first experiment was confirmed in an independent repeat experiment. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.