Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in all strains tested (equivalent to OECD TG 471) (Pharma, 1987).
Cytogenicity in mammalian cells: ambiguous without activation in L5178Y cells (similar to OECD TG 473) (Litton Bionetics, 1978).
Mutagenicity in mammalian cells: negative with and without activation in L5178Y mouse lymphoma cells (similar to OECD 476) (Litton Bionetics, 1978).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-06-03 to 1987-07-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
other: Ames et al. 1973
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: Salmonella typhimurium: TA 98, TA 100, TA 1535, TA1537, TA1538 and Escherichia coli WP2uvrA
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
See table 1.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
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 (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)
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:
other: N-Methyl-N-nitro-N-nitrosoguanidine
Remarks:
WP2uvrA (without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
All strains (with activation)
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)
Details on test system and experimental conditions:
ACTIVATION: Male Sprague Dawley rats (200-300g) were dosed with 500 mg/ kg bw Aroclor 1254 5 d before sacrifice. Livers from 5-6 animals were polled and used to prepare S9 homogenate. S9 mix included 10% v/v S9, 8 mM MgCl2, 33 mM KCl, 5mM glucose-6-phosphate, 4 mM NADP+ and 100 mM phosphate buffer pH 7.4. 0.5 ml of S9 mix were added to 2 ml top agar, 0.1 ml bacterial culture and 0.1 ml test substance solution (total volume 2.7 ml) giving a final concentration of S9 of approximately 2%.

METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Exposure duration:

SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays): 48-72 hours

NUMBER OF REPLICATIONS: 3 plates per test concentration. The experiment was repeated.

DETERMINATION OF CYTOTOXICITY

- Method: other: Background lawn assessment
Evaluation criteria:
Mutagenicity of the test substance is indicated by an increase in the number of revertant colonies.
Statistics:
Statistical methods: Responses (numbers of revertants) to the test substance were compared to concurrent negative and positive 
controls, as well as to historical data.
Species / strain:
other: Salmonella typhimurium: TA 98, TA 100, TA 1535, TA1537, TA1538 and Escherichia coli WP2uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: >1500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
The test compound was toxic to most of the bacterial strains and precipitate was observed at doses greater than or equal to 2500 ug/plate, both with and without metabolic activation.  Final mutagenicity testing was conducted with 5000 ug/plate as the top dose.  The results of the tests conducted on the test substance in the absence or presence of a metabolic activation system were all negative.
Revertants per plate for positive control substances ranged from 18- 680, depending on the agent and strain.

 

Table 2 : Exp 1 : Mutagenicity assay for all strains with and without metabolic activation (mean of 3 plates)

 

TA98

TA100

TA1535

Conc.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

25

30

No

158

175

No

13

12

No

4

21

29

No

153

159

No

12

11

No

20

19

28

No

148

174

No

11

12

No

100

23

28

No

152

181

No

12

10

No

500

27

24

No

148

187

No

14

12

No

2500

18

23

No

166

174

No

8

14

No

10,000

-

3

Yes

-

-

Yes

6

2

Yes

Positive Control

364

437

No

554

611

No

404

119

No

*solvent control with Acetone

 

Table 2 : Exp 1 : Mutagenicity assay for all strains with and without metabolic activation (mean of 3 plates)

 

TA1537

TA1538

WP2uvrA

Conc.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

12

8

No

17

17

No

47

52

No

4

9

8

No

16

20

No

43

51

No

20

7

8

No

13

20

No

44

53

No

100

7

9

No

16

22

No

40

48

No

500

8

5

No

16

24

No

46

57

No

2500

8

6

No

16

11

No

43

41

No

10,000

-

0

Yes

4

1

Yes

-

12

Yes

Positive Control

155

84

No

591

547

No

241

174

No

*solvent control with Acetone

 

Table 3 : Exp 2 : Repeat Assay Number of revertants per plate (mean of 3 plates)

 

TA98

TA100

TA1535

Conc.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

19

32

No

168

205

No

16

13

No

4

27

40

No

153

234

No

17

13

No

20

23

36

No

180

2335

No

17

13

No

100

26

35

No

182

197

No

15

12

No

500

24

27

No

141

207

No

11

16

No

2500

24

29

No

183

207

No

16

16

No

5000

-

25

Yes

119

167

No

13

16

No

Positive control

249

377

No

483

628

No

308

76

No

*solvent control with Acetone

 

Table 3 : Exp 2 : Repeat Assay Number of revertants per plate (mean of 3 plates)

 

TA1537

TA1538

WP2uvrA

Conc.
(
µg/plate)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

12

9

No

14

23

No

48

75

No

4

8

9

No

13

26

No

61

68

No

20

9

8

No

13

26

No

59

58

No

100

9

7

No

15

20

No

63

52

No

500

8

7

No

12

23

No

50

35

No

2500

9

10

No

16

19

No

39

37

No

5000

4

6

Yes

14

18

No

23

26

Yes

Positive control

94

91

No

458

515

No

365

304

No

*solvent control with Acetone

 

 

Conclusions:
Dichlorodimethylsilane has been tested for mutagenicity to bacteria according to a protocol similar to the current guideline. The test substance did not demonstrate genetic activity in any of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA1537, TA1538 and Escherichia coli WP2uvrA, up to cytotoxic concentration, with or without metabolic activation. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is not mutagenic to bacteria under the conditions of the test.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-01-28 to 1980-03-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The restrictions were that only 50 cells were scored.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
50 cells/dose counted, guideline requires 200
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Fischer's medium

- Properly maintained: yes
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced mouse liver S9
Test concentrations with justification for top dose:
0.2, 0.4, 0.8, 0.16, 0.32, 0.64 µl/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
Untreated negative controls:
yes
Remarks:
medium only
Negative solvent / vehicle controls:
yes
Remarks:
ethanol (1% of final volume)
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
- MA
Untreated negative controls:
yes
Remarks:
medium only
Negative solvent / vehicle controls:
yes
Remarks:
ethanol (1% of final volume)
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Dimethylnitrosamine
Remarks:
+ MA
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium


DURATION

- Preincubation period: none

- Exposure duration: 4 hours

- Expression time (cells in growth medium): 24

- Fixation time (start of exposure up to fixation or harvest of cells): 28


SPINDLE INHIBITOR (cytogenetic assays): colcemid (concentration 2 * 10^-7 M)


STAIN (for cytogenetic assays): 5% Giemsa


NUMBER OF REPLICATIONS: 1


NUMBER OF CELLS EVALUATED: 50 per dose


DETERMINATION OF CYTOTOXICITY

- Method: toxicity was measured in a preliminary study, no further details reported.


OTHER EXAMINATIONS:

- Determination of polyploidy: yes

- Determination of endoreplication: no
Evaluation criteria:
Gaps were not counted as significant aberrations, open breaks were considered indicators of genetic damage, as were configurations resulting from the abnormal repair of breaks such as multiradials, rings and multicentrics. Pulverised cells and chromosomes were not included in the count since the number of aberrations is unknown. The estimated number of breaks involved in production of the different aberrations of cells observed, the frequency of cells with more than one aberration, and any evidence for increasing amount of damage with increasing dose, were taken into account in order to establish if the test substance is considered clastogenic.
Statistics:
Student t-test and blind scoring of aberrations.
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Remarks:
toxicity was measured but the results not reported.
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS

- Water solubility: measured, but not reported.

- Other confounding effects: no


RANGE-FINDING/SCREENING STUDIES: a screening test was conducted however the details were not reported.


COMPARISON WITH HISTORICAL CONTROL DATA: the negative control data falls within the an acceptable range of the historical control data.


ADDITIONAL INFORMATION ON CYTOTOXICITY: toxicity was determined as mitotic index - reported in tables below.

Table 1a: Results of chromosome analysis, without metabolic activation (total of 50 cells).

 

Concentration (µl/ml)

Number and type of aberrations

Cells with >1 aberration (%)

Mitotic index

Negative control

1 tb

0

4.8

Solvent control

15

0

6.4

Positive control

1f, 1af

0

1.1

0.2

2tb

0

6.8

0.4

3tb 2f 1t

1

7.2

0.8

2af

0

7.6

0.16

1af

0

7.0

0.32

2tb, 2f, 2af, 1min

1

5.4

0.64

TOXIC

-

-

 Where the negative control is medium, solvent control is ethanol and the positive control is ethylmethanesulfonate (0.5 μl/ml)

Table 1b: Results of chromosome analysis, with metabolic activation (total of 50 cells).

Concentration (µl/ml)

Number and type of aberrations

Cells with >1 aberration (%)

Mitotic index

Negative control

3tb, 1f, 1af

0

6.0

Solvent control

0

0

4.7

Positive control

6tb, 6f, 7t, 1tr, 1qr, 1min

4

3.3

0.2

2tb, 3f, 4af

2

4.5

0.4

2tb

1

7.2

0.8

3tb, 3f, 3af

1

7.3

0.16

3tb, 3af

1

6.0

0.32

0

0

0.4

0.64

2tb, 1f, 2af, 1t

1

4.7

 Where the negative control is medium, solvent control is ethanol and the positive control dimethylnitrosamine (0.3 μl/ml).

Abbreviations of aberration type: af = acentric fragment; t = translocation; tb = chromatid break; f = fragment; qr = quadriradial; min = minute chromosome.

Conclusions:
Dichloro(dimethyl)silane was tested in mouse lymphoma cells with and without metabolic activation according to a protocol similar to OECD 473 and induced an elevated number of structural chromosomal aberrations, though there was no increase in the number of cells with two or more aberrations. Appropriate positive and solvent controls were included and gave expected results. Therefore it is concluded that the test material is ambiguous for cytogenicity under the conditions of the test.
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
no duplicates though test repeated. Concurrent positive controls did not stain
Principles of method if other than guideline:
The procedure used is a modification of that reported by Clive and Spector (Mutation Research, 31:17-29, 1975).
GLP compliance:
no
Type of assay:
mammalian cell gene mutation assay
Species / strain / cell type:
other: mouse lymphoma (L5178Y)
Metabolic activation:
with and without
Metabolic activation system:
Mouse Liver S9
Test concentrations with justification for top dose:
without activation was 0.02 - 0.32 µl/ml; with activation the dose range used was 0.04 - 0.64 µl/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethanol
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
(without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
N-dimethylnitrosamine
Remarks:
(with activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
(without activation)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
(with activation)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION

- Exposure duration: 4 hours

- Expression time (cells in growth medium): 3 days

- Selection time (if incubation with a selection agent): 10 days

NUMBER OF REPLICATIONS: 3 plates per concentration

DETERMINATION OF CYTOTOXICITY

- Method: loss in growth potential of cells (relative total growth)
Evaluation criteria:
The test substance was evaluated for its ability to induce point mutations.

Toxicity is defined by a 50 % or greater reduction in growth compared with the solvent control.
Statistics:
Cells counted. Relative suspension growth (% of control), total mutant and viable clones, relative cloning efficiency, % relative growth and mutant frequency calculated.
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 0.64 µl/ml with activation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: Positive controls were within range of historical control data

Table 2 : Results of Mammalian Mutagenicity assay  with L5178Y Mouse Lymphoma cells

Concentration µl/ml

Mutant* Frequency

Mutant* Frequency

%Relative

 Growth.

%Relative

 Growth.

Cytotoxicity
(yes/no)

 

— MA

+ MA

— MA

+ MA

-

Solvent Control

13.3

38.8

100

100

No

Negative Control

21.7

12.5

113.2

113.8

No

0.02

16.2

-

114.8

-

No

0.04

29.6

24.6

55

87.5

No

0.08

26.1

27.2

102.7

99.1

No

0.16

14.2

33.7

67

91

No

0.32

23.1

26.3

79.4

103.8

No

0.64

-

21.7

-

23.9

Yes

Positive Control

508.5

221.5

25.7

28.2

Yes

*Per 104 surviving cells

Solvent control with Ethanol

Conclusions:
Dichloro(dimethyl)silane did not induce point mutations at any dose level, with or without metabolic activation when tested for mutagenicity to mammalian cells according to a protocol that is similar to OECD TG 476. Appropriate positive, solvent and test medium controls were included and gave expected results. The test substance is considered to be negative for mutagenicity in mouse lymphoma L5178Y cells under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Negative in rat chromosome aberration assay (US EPA guideline test, similar to OECD 475) (Bioassay systems corporation, 1982).

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981-02-04 to 1981-12-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
mitotic index was determined in only 500 cells per animal, results are not presented in compliance with current guideline.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
number of cells evaluated; only male animals used
Qualifier:
according to
Guideline:
other: EPA TAP 22: 269-275, 1972 modified 12/3 to 12/5 1980
Deviations:
not specified
GLP compliance:
yes
Type of assay:
chromosome aberration assay
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gofmoor Farms, Westboro, MA (range-finding study); Charles River, Wilmington, MA USA (main study)
- Age at study initiation: 10-14 weeks
- Weight at study initiation: 200-250 g
- Assigned to test groups randomly: not reported
- Fasting period before study:
- Housing: 5 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50


Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: paraffin oil
- Justification for choice of solvent/vehicle: none given
- Concentration of test material in vehicle: not reported
- Purity: laboratory grade
Duration of treatment / exposure:
single injection
Frequency of treatment:
Once
Post exposure period:
sacrifice at 6, 24 and 48 hours after exposure.
Dose / conc.:
5 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
Dose / conc.:
11 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
Dose / conc.:
22 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
Dose / conc.:
32 mg/kg bw/day
Remarks:
Criteria for selection of MTD based on the results of a range-finding study
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
- cyclophosphamide;
- Justification for choice of positive control(s): none given
- Route of administration: not reported
- Doses / concentrations: 22 mg/kg
Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: Based on range finding study

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):

DETAILS OF SLIDE PREPARATION: Cells were centrifuged and resuspended three times in fixative (3:1 methanol:acetic acid). Aliquots of suspended cells were air dried. Slides of acceptable quality were stained with 5% Giesma, and photographed using x100 objective.

METHOD OF ANALYSIS: Negatives were projected onto a white counter and examined for chromosomal breaks or gaps, chromatid breaks or gaps, complex rearrangements, pulverised cells or chromosomes, acentric fragments, polyploidy and large translocations or deletions.

Evaluation criteria:
None given in report
Statistics:
Chi squared test and Wilcoxon test.
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
deaths at 22 mg/kg and above
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

 Table 1: Results of range-finding studies

 

Dose level mg/kg

Number dead/number animals

54

3/10

43

5/10

32

0/10

22

2/10

11

0/10

5

0/10

Table 2: Results of chromosome analysis in bone marrow(5 animals per dose, approx 110 cells per animal evaluated)

 

 -

Positive control

Vehicle control

11mg/kg

22 mg/kg

32 mg/kg

Sampling time (h)

24

6

24

48

6

24

48**

6

24

48

6

24

48

Gaps

46-60

0-4

0-6

0-4

2-6

1-7

0-1

1-5

0-4

0-2

2-10

1-7

1-5

 Breaks

ND

0-4

0-2

0-3

0-5

0-7

0-2

0-2

0-2

0-2

1-5

0-5

1-2

 Other

3-<23

0-2*

0-1*

0-1*

0

0-2*

0-2*

0

3

0-2*

0

0-2*

0

Mitotic index %

1.3-3.1

1.7-5.0

1.4-3.7

1.2-4.9

0.8-5.8

2.1-5.8

1.0-4.3

2.0-4.7

1.8-5.8

1.4-3.6

2.3-4.5

1.8-4.3

1.7-3.4

Polyploidy

0

0

0

0

0

0

0

0

0

0

0

0

Endo reduplication

0

0

0

0

0

0

0

0

0

0

0

0

Numbers in table represent the range of the mitotic index or the total number of gaps, breaks or other aberrations recorded for each test animal

ND Not determined

* deletions

** 7 animals used at this dose and time, 2 with under 50 analysable cells.

Conclusions:
Dichloro(dimethyl)silane has been tested according to a protocol similar to OECD TG 475. The test substance did not induce chromosome aberrations when tested in male rats by ip injection at doses up to 32 mg/kg bw. Appropriate positive and vehicle controls were included and gave expected results. It is concluded that the test substance is not genotoxic under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Data are available for dichloro(dimethyl)silane for all the required endpoints for in vitro genetic toxicity. Most of the studies gave negative results. The exception was an in vitro cytogenicity study (similar to OECD 473) which gave an equivocal result (Litton Bionetics, 1978). The possibility of cytogenetic effects in vivo has been examined in an in vivo chromosome aberration study which gave a negative result.

Dichloro(dimethyl)silane has been tested for mutagenicity to bacteria according to a protocol similar to OECD TG 471 (Pharma, 1987). The test substance did not demonstrate genetic activity in any of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA1537, TA1538 and Escherichia coli WP2uvrA, up to cytotoxic concentration, with or without metabolic activation. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the test substance is not mutagenic to bacteria under the conditions of the test. The result is supported by negative results in a study using Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA1537 and TA 1538 (Dow Corning Corporation, 1977; Litton Bionetics, 1978), and in a study that tested Salmonella typhimurium strain TA 98, TA 100, TA 1535 and TA 1537 (Bayer, 1984).

Dichloro(dimethyl)silane was tested in mouse lymphoma cells with and without metabolic activation according to a protocol similar to OECD TG 473 and induced an elevated number of structural chromosomal aberrations, though there was no increase in the number of cells with two or more aberrations (Litton Bionetics, 1978). Appropriate positive and solvent controls were included and gave expected results. Therefore it is concluded that the test material is ambiguous for cytogenicity under the conditions of the test. An ambiguous result was also reported in an in vitro sister chromatid exchange assay, also conducted in mouse lymphoma L5178Y cells (Litton Bionetics, 1978).

Dichloro(dimethyl)silane did not induce point mutations at any dose level, with or without metabolic activation when tested for mutagenicity to mammalian cells according to a protocol that is similar to OECD TG 476 (Litton Bionetics, 1978). Appropriate positive, solvent and test medium controls were included and gave expected results. The test substance is considered to be negative for mutagenicity in mouse lymphoma (L5178Y) cells under the conditions of the test.

Dichloro(dimethyl)silane has been in vivo tested according to a protocol similar to OECD TG 475 (Bioassay systems corporation, 1982). The test substance did not induce chromosome aberrations when tested in male rats by ip injection at doses up to 32 mg/kg bw. Appropriate positive and vehicle controls were included and gave expected results. It is concluded that the test substance is not genotoxic under the conditions of the test.

It is considered that as the ambiguous results obtained in the in vitro cytogenicity (chromosome aberration and sister chromatid exchange) assays were not confirmed in the in vivo chromosome aberration assay, the registered substance is not clastogenic and further in vivo testing is not required.


Justification for classification or non-classification

Based on the available in vitro and in vivo information for genetic toxicity, dichloro(dimethyl)silane is not classified for mutagenicity according to Regulation (EC) No 1272/2008.