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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:
2000-10-06 - 2001-01-03
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
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(triethoxysilyl)propanethiol
EC Number:
238-883-1
EC Name:
3-(triethoxysilyl)propanethiol
Cas Number:
14814-09-6
Molecular formula:
C9H22O3SSi
IUPAC Name:
3-(triethoxysilyl)propanethiol
Constituent 2
Reference substance name:
014814-09-6
Cas Number:
014814-09-6
IUPAC Name:
014814-09-6
Test material form:
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:
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:
Without metabolic activation: 50, 150, 500, 1500 and 5000 µg/plate; with metabolic activation - 5.0, 15, 50, 150, 500, 1500 and 5000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: Based on the sponsor's request due to compatibility with the target cells and solubility of the test article
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA1537 without metabolic activation 75 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene 1.0 µg/plate and 10 µg/plate
Remarks:
TA98, TA100, TA1535, TA1537 - 1.0 µg/plate and WP2 uvrA - 10 µg/plate all with metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
WP2 uvrA without metabolic activation 1000 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA98 without metabolic activation 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:
TA100 and TA1535 without metabolic activation 1.0 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation

ACTIVATION: S9 mix contained 10% S9, glucose-6-phosphate and NADP as co-factors. 0.5 ml S9 mix, 100 µl of tester strain and 25 µl of vehicle or test article were added to 2ml top agar, giving a final concentration of approximately 2% S9.

DURATION
- Preincubation period: 60+/-2 minutes at 37ºC
- Exposure duration: 48 - 72 hours at 37ºC+/-2ºC

SELECTION AGENT (mutation assays): histidine deficient agar

NUMBER OF REPLICATIONS: triplicate plates, experiment repeated

DETERMINATION OF CYTOTOXICITY
- Method: other: condition of background lawn

Evaluation criteria:
A result is positive if the increase in mean revertants at the peak of the dose response in strains TA1535 and TA1537 is equal to or greater than three times the mean negative control value. In strains TA 98, TA 100 and E. coli WP2 uvrA the result is considered positive if the increase in mean revertants at the peak of the dose response is equal to or greater than two times the mean negative control value.
Statistics:
None stated in report

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
Remarks:
toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.
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
Remarks:
toxicity observed at 667 µg/plate with metabolic activation, none was observed without metabolic activation thus 5000 µg/plate was highest dose without metabolic activation. No precipitate was observed.
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS

COMPARISON WITH HISTORICAL CONTROL DATA: yes

Any other information on results incl. tables

Summary of results – Experiment B1

Dose µg/ml

+/- metabolic activation

Average revertants per plate (mean of 3 plates)

TA98

TA100

TA1535

TA1537

WP2 uvrA

Solvent control

-

14

90

13

5

13

50

-

15

83

11

6

14

150

-

14

74

11

5

11

500

-

13

53

12

5

11

1500

-

12

36

7

4

10

5000

-

9

14

8

3

6

Positive control

-

282

557

595

1490

90

Solvent control

+

23

94

15

7

13

5.0

+

16

94

13

8

n.t.

15

+

15

101

16

7

 n.t.

50

+

16

84

12

7

13

150

+

14

93

8

5

14

500

+

11

11

8

4

11

1500

+

2

10

6

2

14

5000

+

n.t

n.t.

n.t.

n.t.

10

Positive control

+

773

941

171

161

66

Repeated assay due to excessive toxicity in Experiment B1

 

Dose µg/ml

+/-

metabolic activation

Average revertants per plate

TA100

TA1537

Solvent control

-

108

6

          15       

-

 

8

50

-

84

11

150

­-

85

6

500

­-

93

6

1500

-

83

7

5000

-

83

6

Positive control

-

407

763

Independent repeat assay

Dose µg/ml

+/- metabolic activation

Average revertants per plate

TA98

TA100

TA1535

TA1537

WP2 uvrA

Solvent control

-

12

86

9

5

12

5.0

-

 n.t

n.t 

 n.t

 n.t

14

15

-

10

95

13

6

11

50

-

13

98

11

5

12

150

-

13

99

11

5

11

500

-

13

113

12

5

12

1500

-

11

70

11

7

15

5000

-

8

63

15

7

n.t 

Positive control

-

92

359

274

752

209

Solvent control

+

26

120

13

7

12

5.0

+

19

116

12

4

 n.t.

15

+

22

105

13

7

10

50

+

26

80

16

5

13

150

+

26

109

11

6

11

500

+

18

97

13

3

14

1500

+

5

66

11

5

13

5000

+

 n.t

 n.t.

 n.t.

 n.t.

12

Positive control

+

509

1129

100

118

290

Repeat assay due to unacceptable vehicle control in independent repeat assay

 

Dose µg/ml

+/-

metabolic activation

Average revertants per plate

WP2 uvrA

Solvent control

-

18

50

-

17

150

­-

16

500

­-

16

1500

-

20

5000

-

19

Positive control

-

597

Applicant's summary and conclusion

Conclusions:
3-(triethoxysilyl)propanethiol has been tested for mutagenicity to bacteria in a study which was conducted according to OECD Test Guideline 471 and in compliance with GLP. No evidence of a test substance related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.