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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:
1977 - 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The study was conducted according to a Litton Bionetics Inc. method but full details are not available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no analytical purity stated; only single cultures tested, tester strains TA 102 or E. coli WP2 were not used in the study as required in the appropriate OECD test guideline
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dimethyldiethoxysilane
- Physical state: colourless liquid

Method

Target gene:
his operon
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
Species / strain / cell type:
E. coli, other: W3110/polA+
Species / strain / cell type:
E. coli, other: P3478/polA-
Species / strain / cell type:
yeast, other: Saccharomyces cerevisiae (D4)
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S9-mix
Test concentrations with justification for top dose:
Main experiment:
- 0.001, 0.01, 0.1, 1, 5 µL/plate (with and without metabolic activation)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: -S9-mix: MNNG: 10 µg/plate (TA 1535, TA 100, D4), QM: 10 µg/plate (TA 1537), NF: 100 µg/plate (TA 1538, TA 98); +S9-mix: ANTH: 100 µg/plate (TA 1535, TA 100), AMQ: 100 µg/plate (TA 1537), AAF: 100 µg/plate (TA 1538, TA 98), DMNA: 100 µM/plate (D4)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Expression time (cells in growth medium): 48 h (Ames test), 24 h (DNA repair test)

NUMBER OF REPLICATIONS: single culture/test concentration

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth


Evaluation criteria:
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 100, TA 1535, TA 1537 and TA 1538, and 2-3 times the solvent control for TA 98 and D4.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium, other: TA 1535, TA1537, TA98, and TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
≥1 µl/plate -S9-mix
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
yeast, other: Saccharomyces cerevisiae (D4)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
E. coli, other: W3110/po1A+
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
E. coli, other: P3478/po1A-
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Marked cytotoxicity was observed in tester strain TA 1538 in the absence of metabolic activation at concentration ≥1 µl/plate. No relevant cytotoxicity was observed for the other tester strains at any concentration either in the presence or in the absence of metabolic activation.

Any other information on results incl. tables

Table 1: Experiment 1 Plate incorporation Number of revertants per plate

 

TA98

TA100

TA1535

Conc.
µg/plate

MA

+

 MA

Cytotoxic
(yes/no)

MA

+ MA

Cytotoxic
(yes/no)

 MA

+ MA

Cytotoxic
(yes/no)

0*

36

44

No

92

134

No

28

14

No

0.001

30

55

No

76

117

No

17

18

No

0.01

26

52

No

88

155

No

16

21

No

0.1

25

43

No

81

142

No

15

15

No

1

34

53

No

84

126

No

16

13

No

5

26

58

No

75

125

No

12

12

No

Positive control

>1000

>1000

No

610

811

No

>1000

299

No

*solvent control with DMSO

Table 2: Experiment 1 Plate incorporation Number of revertants per plate

 

TA 1537

TA 1538

D4

Conc.
µg/plate

MA

+ MA

Cytotoxic
(yes/no)

MA

+

MA

Cytotoxic
(yes/no)

 MA

+ MA

Cytotoxic
(yes/no)

0*

14

15

No

28

31

No

44

154

No

0.001

30

14

No

15

31

No

48

222

No

0.01

19

26

No

26

31

No

42

64

No

0.1

22

19

No

23

29

No

46

202

No

1

14

18

No

14

30

No

43

234

No

5

10

13

No

15

35

No

50

228

No

Positive control

>1000

392

No

701

>1000

No

746

242

No

*solvent control with DMSO

Applicant's summary and conclusion

Conclusions:
No mutagenic effect was observed for the test substance tested up to cytotoxic concentration in any of the test strains in two independent experiments without and with metabolic activation. The test substance is non-mutagenic in test strains used.