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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted under GLP according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were that only four strains or bacteria tested.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
Ames et al. (1973, 1975); Maron and Ames (1983)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Dichloro(methyl)silane
EC Number:
200-877-1
EC Name:
Dichloro(methyl)silane
Cas Number:
75-54-7
Molecular formula:
CH4Cl2Si
IUPAC Name:
dichloro(methyl)silane

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Rat liver; Induced by Aroclor 1254
Test concentrations with justification for top dose:
1st test: 20, 100, 500, 2500, 12500 µg/plate
2nd test: 75, 150, 300, 600, 1200, and 2400 µg/plate
Vehicle / solvent:
The solvent (negative control) for the test substance was ethylene glycoldimethylether anhydrous (EGDME), and for the positive controls, dimethylsulfoxide (DMSO). 
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
See table 1
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk


DURATION

- Exposure duration: 48 h
- Expression time (cells in growth medium): 48 h


NUMBER OF REPLICATIONS: 4 plates per strain and dose


DETERMINATION OF CYTOTOXICITY
- Method: other: reduction in background lawn; reduction in mutant count relative to control; total bacterial count

Evaluation criteria:
Responses (number of revertants) to the test substance were compared to concurrent negative and positive controls, as well as to historical data.

Results and discussion

Test results
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:
100 μg/plate strain TA 98
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: The positive and solvent control results were acceptable in comparison with historical contro data.

ADDITIONAL INFORMATION ON CYTOTOXICITY: At all tested doses, the test substance had a strong strain-specific bacteriotoxic effect, so that this range could only be used to a limited extent up to 2500 µg/plate for evaluation purposes.  



Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 3a Experiment 1- Mutagenicity Assay. Number of revertants per plate (mean of 3 plates).

Strain

 

TA 1535

TA 100

Conc. (μg/plate)

- MA

+ MA

Cytotoxic

(yes/no)

-MA

+ MA

Cytotoxic

(yes/no)

0*

15

11

no

84

111

no

20

17

13

no

82

113

no

100

23

12

no

77

128

no

500

20

11

no

84

107

no

2500

17

15

no

67

145

no

12500

0

--

yes

0

---

yes

Positive control

766

162

-

248

366

-

* Solvent control EDGMA

Table 3b Experiment 1- Mutagenicity Assay. Number of revertants per plate (mean of 3 plates).

Strain

 

TA 1537

TA 98

Conc. ()

- MA

+ MA

Cytotoxic

(yes/no)

-MA

+ MA

Cytotoxic

(yes/no)

0*

9

6

no

18

146

no

20

10

8

no

19

91

no

100

11

7

no

16

51

yes**

500

10

6

no

20

41

yes**

2500

7

3

no

7

64

yes**

12500

0

-

yes

0

--

yes**

Positive control

78

34

-

78

400

-

* Solvent control EDGMA

** Reduction in mean number of revertants to <50% solvent control (reviewer's judgement)

Table 4a Experiment 2- Mutagenicity Assay. Number of revertants per plate (mean of 3 plates).

Strain

 

TA 1535

TA100

Conc. (μg/plate)

- MA

+ MA

Cytotoxic

(yes/no)

-MA

+ MA

Cytotoxic

(yes/no)

0*

20

24

149

206

75

21

19

no

136

199

no

150

18

23

no

148

195

no

300

19

18

no

150

170

no

600

22

18

no

140

185

no

1200

20

18

no

133

151

no

2400

18

12

no

88

87

yes**

Positive control

799

386

-

451

1014

-

* Solvent control EDGMA

** Reduction in mean number of revertants to <50% solvent control (reviewer's judgement)

Table 4b Experiment 2- Mutagenicity Assay. Number of revertants per plate (mean of 3 plates).

Strain

 

TA 1537

TA98

Conc. (μg/plate)

- MA

+ MA

Cytotoxic

(yes/no)

-MA

+ MA

Cytotoxic

(yes/no)

0*

11

11

23

35

75

10

15

no

25

31

no

150

9

11

no

22

25

no

300

9

13

no

24

33

no

600

10

9

no

16

36

no

1200

8

10

no

21

23

no

2400

6

6

no

14

24

no

Positive control

96

83

-

122

627

-

* Solvent control EDGMA





 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The test substance, dichloromethylsilane (CAS No. 75-54-7), did not demonstrate genetic activity in any of the tests conducted in this evaluation, both with and without metabolic activation. The results indicate that the test substance was not considered mutagenic under these test conditions.