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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:
2000-09-01 to 2000-10-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3-trimethoxysilylpropane-1-thiol
EC Number:
224-588-5
EC Name:
3-trimethoxysilylpropane-1-thiol
Cas Number:
4420-74-0
Molecular formula:
C6H16O3SSi
IUPAC Name:
3-trimethoxysilylpropane-1-thiol

Method

Target gene:
histidine operon (Salmonella strains)
tryptophan operon (E. coli strain)
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
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:
preliminary assay: 5000 µg/plate
75-5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: compatibility with the target cells
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, + MA, 1.0 µg/plate (Salmonella) 10 µg/plate (E. coli)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA 98, - MA, 1.0 µg/plate
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, - MA, 1.0 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA 1537, - MA, 75 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
WP2 uvrA, - MA, 1000 µg/plate
Details on test system and experimental conditions:
ACTIVATION:
S9 mix:
- 10% S9
- 5 mM glucose-6-phosphate
- 4 mM ß-nicotinamide-adenine dinucleotide phosphate
- 8 mM MgCl2
- 33 mM KCl
- 100 mM phosphate buffer (pH 7.4)

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 60±2 min at 37±2°C
- Exposure duration: 48-72 hours at 37±2°C

SELECTION AGENT (mutation assays): minimal agar

NUMBER OF REPLICATIONS: triplicate plates; 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of bacterial background lawn
Evaluation criteria:
For the test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain over a minimum of two increasing concentrations of test article.
Data sets for TA 1535 and TA 1537 were judged positive if the increase in mean revertants is ≥ 3x the mean vehicle control value.
Data sets for TA 98, TA 100 and WP2 uvrA were judged positive if the increase in mean revertants is ≥ 2x the mean vehicle control value.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: No mutagenic potential

Any other information on results incl. tables

Preliminary toxicity assay: number of revertants per plate

Concentration (µg/plate)

TA 98

TA 100

TA 1535

TA 1537

WP2 uvrA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

Vehicle

22

12

128

118

18

14

7

5

15

1

6.7

25

14

125

128

22

17

4

4

11

1

10

19

10

103

112

23

13

5

3

19

1

33

24

16

113

110

17

14

4

3

17

1

67

22

19

93

C

18

11

5

4

14

1

100

23

17

132

111

21

21

4

3

12

1

333

21

11

99

100

18

18

4

4

10

1

667

26

11

111

102

12

16

5

5

16

1

1000

25

16

99

116

19

17

4

4

14

1

3333

21

10*

98

81*

17

10*

6

2*

22

1

5000

18*

7**

64**

0***

14*

0***

2***

0***

13*

14**

* = background lawn slightly reduced

** = background lawn severely reduced

*** = background lawn extremely reduced

C = contaminated

 

Experiment B1: Number of revertants per plate (mean of 3 plates)

Concentration (µg/plate)

TA 98

TA 100

TA 1535

TA 1537

WP2 uvrA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

Vehicle

20

21

92

116

12

9

5

7

10

12

100

19

26

99

115

-

13

-

7

13

10

105

-

-

-

-

10

-

6

-

-

-

333

22

29

87

119

-

10

-

5

14

12

348

-

-

-

-

12

-

6

-

-

-

1000

25

26

93

95

-

10

-

6

10

11

1045

-

-

-

-

10

-

4

-

-

-

3333

18

25

63**

79*

-

7**

-

4*

11

10

3485

-

-

-

-

9*

-

3**

-

-

-

5000

1***

7**

4***

60**

0***

1***

0****

0***

10*

10

Positive control

567

608

408

488

231

35

580

40

368

162

* = background lawn slightly reduced

** = background lawn severely reduced

*** = background lawn extremely reduced

**** = background lawn absent

Experiment B2: Number of revertants per plate (mean of 3 plates)

Concentration (µg/plate)

TA 98

TA 100

TA 1535

TA 1537

WP2 uvrA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

- MA

+ MA

Vehicle

13

13

85

97

6

8

4

8

11

10

75

13

15

86

108

9

7

3

4

10

12

200

15

19

89

123

9

7

3

5

11

15

600

12

16

98

85

10

7

4

4

11

10

1800

10*

16

78*

100

3**

9

3*

4

9*

11

5000

0***

0***

0***

0***

0***

8**

0***

1***

7**

10*

Positive control

308

258

311

385

94

39

218

45

266

57

* = background lawn slightly reduced

** = background lawn severely reduced

*** = background lawn extremely reduced

Applicant's summary and conclusion

Conclusions:
3-Trimethoxysilylpropane-1-thiol has been tested in a valid bacterial reverse mutation assay, according to the OECD TG 471 (1989), and under GLP, using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 or E.coli WP2 uvrA.
No increase in the number of revertants was observed in any test strain, with or without metabolic activation. Appropriate positive and solvent controls were added and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.