1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine

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:

1989-05-10 to 1989-10-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The restrictions were that the range of strains does not comply with the current guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1981

Deviations:

yes

Remarks:

The range of strains does not comply with the current guideline

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine

EC Number:

253-634-7

EC Name:

1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine

Cas Number:

37697-65-7

Molecular formula:

C13H33N3Si

IUPAC Name:

{bis[(butan-2-yl)amino](methyl)silyl}(butan-2-yl)amine

Test material form:

other: 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:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

biphenyl polychloride induced rat liver S9

Test concentrations with justification for top dose:

0.1, 0.5, 1, 2.5 and 5 ml/plate

Vehicle / solvent:

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

- Justification for choice of solvent/vehicle: no justification given in study 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 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, TA 1538 (without activation)

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

TA 100 (without activation)

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

TA 1535 (without activation)

Controls 5

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)

Details on test system and experimental conditions:

ACTIVATION: Cofactors were added to the S9 mix to reach the following concentrations: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 4 mM NADP in 100 mM potassium-phosphate-buffer pH 7.4. The concentration of S9 in the mix was 5%, and 0.5 ml of S9 mix were added to test substance, overlay agar and bacterial suspension giving a final concentration of approximately 1% S9 in the plates.

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION

- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3 plates for each test concentration; experiment repeated

DETERMINATION OF CYTOTOXICITY
- Method: reduction in mean number of revertants, background lawn assessment

Evaluation criteria:

A result is positive if the number of colonies apparent in the presence of the test article is greater or equal to twice the number of colonies apparent in the negative control.

Statistics:

The mean number of colonies apparent in the dishes and the standard deviation were calculated.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

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

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 2.5 mg/plate (Strain TA98 without metabolic activation)

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

2.5 mg/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)

	TA100 (-MA)
Conc. (mg/dish)	Plate 1	Plate 2	Cytotoxic (yes/no)
0*	87	95	No
0.05	103	83	No
0.1	81	85	No
0.5	98	77	No
1	80	74	No
2.5	96	91	No
5	103	99	No

*solvent control with Acetone

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

	TA98			TA100			TA1538
Conc. mg/dish	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	24	28	No	95.3	101	No	41.3	43	No
0.1	23	31.3	No	87.7	99	No	34.7	44	No
0.5	25.3	37	No	88.7	98.3	No	37.7	47.7	No
1	29.7	29	No	98	104.7	No	25	38.7	No
2.5	26.7	31.3	Yes	78.7	97.3	No	21	35	No
5	27.3	40	Yes	84	99.3	Yes	7.3	24.3	Yes
Positive control	551.5	1135.5	No	308.5	1538	No	240	1258	No

*solvent control with Acetone

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

	TA1535			TA1537
Conc. mg/dish	—  MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	8.3	10.7	No	10	10.3	No
0.1	9	11.7	No	13.7	10	No
0.5	7	9.7	No	12	8.3	No
1	8.3	9.3	No	10	9	No
2.5	9	8.7	No	7.3	8.7	No
5	3	10	Yes	3	5	Yes
Positive control	1002.5	185	No	331.5	93.5	No

*solvent control with Acetone

Table 4: Experiment 2 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA98			TA100			TA1538
Conc. mg/dish	— MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)	— MA	+  MA	Cytotoxic (yes/no)
0*	30	24.3	No	109	107	No	41.3	43	No
0.1	18	32.3	No	113.7	111.3	No	34.7	44	No
0.5	26.7	24.3	No	117.7	127.3	No	37.7	47.7	No
1	23.3	25.3	No	107.7	104.7	No	25	38.7	No
2.5	17.7	32.3	Yes	147	124.7	No	21	35	Yes
5	3.3	20	Yes	64.3	92.3	Yes	7.3	24.3	Yes
Positive control	408.5	1106	No	293.5	1118.5	No	240	1258	No

*solvent control with Acetone

Table 4: Experiment 2 Plate incorporation Number of revertants per plate (mean of 3 plates)

	TA1535			TA1537
Conc. mg/dish	—  MA	+ MA	Cytotoxic (yes/no)	— MA	+ MA	Cytotoxic (yes/no)
0*	11.3	11.7	No	11.3	7.7	No
0.1	9.7	10.3	No	11	8	No
0.5	10	13.7	No	10	9	No
1	8.7	15	No	12.3	8.3	No
2.5	11	10	No	5.7	8.7	Yes
5	7.7	8	Yes	0.3	9.3	Yes
Positive control	1295.5	133	No	216.5	62.5	No

*solvent control with Acetone

Applicant's summary and conclusion

Conclusions:

1-Methyl-N,N',N''-tris(1-methylpropyl)silanetriamine has been tested for mutagenicity to bacteria in a study conducted according to OECD 471 (1981) and in compliance with GLP. No test-substance induced increase in the number of revertants was observed for the test substance up to limit concentrations in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 or TA 1538 without and with metabolic activation in two independent experiments. It is concluded that the the test substance is not mutagenic to bacteria under the conditions of the test.