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Toxicological information

Genetic toxicity: in vitro

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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

Constituent 1
Chemical structure
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 / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
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.
Controlsopen allclose all
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)
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)
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)
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)
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 resultsopen allclose all
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
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.

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