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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro:

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typimuriumstrains TA 98, TA 100, TA 102, TA 1535, and TA 1537 (according to OECD TG 471)

Cytogenicity in mammalian cells: negative with and without metabolic activation in L5178Y cells (similar to OECD TG 473)

Mammalian gene mutation: This information will be submitted later based on ECHA decision number CCH-D-2114428794-40-01/F

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:
17-05-2002 To 02-12-2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
his operon
Species / strain / cell type:
S. typhimurium TA 102
Additional strain / cell type characteristics:
other: rfa- and pkM101
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
other: rfa-, uvrB- and pkM101 (TA 98 & TA100)
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.
Test concentrations with justification for top dose:
100, 316, 1000, 3160 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used:DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-anthracene amide
Remarks:
+S9; TA 98, TA102 and TA1537: 2 µg/plate dissolved in DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
-S9: TA1537: 100 µg/plate dissolved in ethanol
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
-S9: TA98: 10 µg/plate in DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
-S9: TA1535 and TA100: 10 µg/plate in water
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
-S9: TA102: 1300 µg/plate dissolved in DMSO.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
+S9; TA100 and TA1535: 1500 µg/plate dissolved in aqua ad iniectabilia.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation) and preincubation.

DURATION
- Preincubation period: 60 minutes (at 37°C)
- Exposure duration: 48 hours (at 37°C)


NUMBER OF REPLICATIONS: 3 plates per concentration in 2 independent experiments


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth and background lawn evaluation.

METABOLIC ACTIVATION SYSTEM: Post-mitochondrial fraction (S9 fraction) from rats treated with Aroclor 1254 was prepared according to Maron and Ames (1983). S9 was collected from 20-30 rats.
The S9 mix was freshly prepared on the day of the test according to Maron and Ames (1983): containing 5% S9 and the following components (per 100 mL):
-5.0 ml rat liver S9 (Aroclor 1254-induced)
-2.0 ml 0.4 M MgCl2 + 1.65 M KCl-salt solution
-141.0 mg glucose-6-phosphate
- 306.5 mg NADP
- 50.0 ml 0.2 M phosphate buffer, pH 7.4
- sterile aqua ad iniectabilia ad 100 ml
Evaluation criteria:
A test chemical is considered to show a positive response if:
- the number of revertants is significantly increased (p ≤0.05, U-test according to MANN and WHITNEY) compared with the solvent control to at least 2-fold of the solvent control for TA-98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both independent experiments;
- in addition, a significant (p ≤0.05) concentration (log value)-related effect (Spearman’s rank) correlation coefficient) is observed;
- positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking random samples on histidine-free agar plates.
Cytotoxicity is defined as a reduction in the number of colonies by more than 50% compared with the solvent control and/or a scarce background lawn.
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
5000 µg/plate without activation, 1000 µg/plate with activation
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
The test substance was examined in a preliminary cytotoxicity test without metabolic activation in test strain TA 100. Ten concentrations ranging from 0.316 to 5000 µg/plate were tested. Cytotoxicity (scarce background lawn) was noted at the top concentration of 5000 µg/plate. Hence, 5000µg/plate was chosen as the top concentration for the main study.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
In the plate incorporation test without metabolic activation cytotoxicity (scarce background lawn) was noted at the top concentration of 5000 µg/plate of the test substance in test strain TA 100. In the experiment with metabolic activation cytotoxicity (reduction of the number of revertants by more than 50%) was noted at concentration of 1000 and 3160 µg of the test substance/ plate in test strain TA 1535.
In the preincubation test without metabolic activation pronounced cytotoxicity (scarce background lawn and reduction of the number of revertants by more than 50%) was noted at the top concentration of 5000 or 3160 µg/plate onwards in test strains TA 1535 and TA 1537, respectively. Cytotoxicity (scarce background lawn) was noted at the top concentration of 5000 µg/plate of test substance in test strain TA 98. In the experiment with metabolic activation pronounced cytotoxicity ((scarce background lawn and reduction of the number of revertants by more than 50%) was noted at the top concentration of 5000 µg/plate in test strain TA 1537, and cytotoxicity (scarce background lawn) in test strain TA 98 and TA 1535.

Table 1. Plate incorporation test without metabolic activation:

Substance (µg/plate)

Plate incorporation test without metabolic activation. Number of reverted colonies.

 

TA 98

TA 100

TA 102

TA 1535

TA1537

Silane M2 Dimethoxy

Mean values ± SD

5000

M

32.3

110.7#

291.7

10.0

3.3

±SD

6.4

19.5

5.5

1.7

1.5

3160

M

30.3

101.0

288.7

8.0

4.3

±SD

5.9

5.6

5.5

1.0

1.2

1000

M

24.7

118.7

317.3

10.0

3.7

±SD

2.5

1.5

25.0

3.5

1.5

316

M

29.0

100.0

255.0

12.3

3.3

±SD

4.4

3.5

10.6

2.9

1.2

100

M

26.3

107.0

265.3

11.0

5.7

±SD

3.5

18.2

7.4

2.0

0.6

Negative control 100 µg/plate

M

25.7

102.7

270.7

10.0

3.3

±SD

2.5

4.7

22.7

1.7

2.1

Positive control substance

 

2-Nitro-fluorene

Sodium azide

Methyl-methane sulfonate

Sodium azide

Aminoacridine

Concentration µg/plate

 

10

10

1300

10

100

 

M

726.0

1129.0

1348.0

540.7

142.7

 

±SD

59.6

46.0

78.3

15.3

32.1

# = scarce background lawn.

Table 2. Plate incorporation test with metabolic activation

Substance (µg/plate)

Plate incorporation test with metabolic activation. Number of reverted colonies.

 

TA 98

TA 100

TA 102

TA 1535

TA1537

Silane M2 Dimethoxy

Mean values ± SD

5000

M

32.3

113.7

241.7

9.3

7.7

±SD

0.6

15.9

17.8

0.6

2.1

3160

M

38.0

113.3

277.7

7.7

4.3

±SD

7.0

11.0

22.5

0.6

1.5

1000

M

34.7

117.0

256.7

7.0

5.7

±SD

7.6

23.6

36.4

1.0

      3.2

316

M

31.3

114.7

371.7

17.7

5.7

±SD

7.1

10.6

46.2

3.5

0.6

100

M

49.0

114.3

284.3

13.3

6.3

±SD

7.0

6.8

11.9

3.5

2.3

Negative control 100 µg/plate

M

38.7

114.7

296.0

16.0

5.0

±SD

1.5

5.0

8.5

3.6

1.7

Positive control substance

 

2-Anthracene amide

Cyclophosphamide

2-Anthracene amide

Cyclophosphamide

2-Anthracene amide

Concentration µg/plate

 

10

10

1300

10

100

 

M

724.0

1118.3

937.0

288.7

138.3

 

±SD

43.3

45.8

14.0

25.9

26.1

Table 3. Preincubation test without metabolic activation

Substance (µg/plate)

Preincubation test without metabolic activation. Number of reverted colonies.

 

TA 98

TA 100

TA 102

TA 1535

TA1537

Silane M2 Dimethoxy

Mean values ± SD

5000

M

18.3#

94.0#

298.7

7.3#

1.7#

±SD

5.5

43.5

12.7

6.4

1.2

3160

M

23.0

134.3

306.7

17.3

2.0#

±SD

5.0

10.6

17.9

0.6

3.5

1000

M

18.3

137.7

294.7

21.3

6.7

±SD

4.5

3.2

14.2

1.5

2.5

316

M

23.7

136.0

309.7

16.0

6.7

±SD

4.5

9.2

8.0

6.9

1.2

100

M

23.0

130.0

318.0

17.0

8.0

±SD

2.0

7.5

8.2

2.0

2.6

Negative control 100 µg/plate

M

22.3

114.0

293.7

18.0

7.7

±SD

5.0

10.8

21.1

6.0

0.6

Positive control substance

 

2-Nitro-fluorene

Sodium azide

Methyl-methane sulfonate

Sodium azide

Aminoacridine

Concentration µg/plate

 

10

10

1300

10

100

 

M

514.0

1131.3

1102.3

234.0

292.0

 

±SD

56.2

101.2

17.9

33.4

56.1

Table 4. Preincubation test with metabolic activation

Substance (µg/plate)

Preincubation test with metabolic activation. Number of reverted colonies.

 

TA 98

TA 100

TA 102

TA 1535

TA1537

Silane M2 Dimethoxy

Mean values ± SD

5000

M

22.0#

144.7

387.0

17.7#

4.0#

±SD

7.0

20.3

60.9

1.5

4.0

3160

M

31.0

135.7

443.0

17.0

5.7

±SD

5.3

15.5

23.6

2.0

3.5

1000

M

26.7

131.7

446.0

16.7

9.7

±SD

2.1

18.2

16.5

1.2

      3.5

316

M

34.3

129.0

407.3

18.3

7.7

±SD

4.2

5.3.6

16.5

1.2

1.2

100

M

32.0

132.0

412.3

17.7

9.3

±SD

12.1

14.9

30.4

1.5

2.1

Negative control 100 µg/plate

M

31.0

128.0

375.7

15.3

8.7

±SD

2.6

15.1

22.1

2.5

2.1

Positive control substance

 

2-Anthracene amide

Cyclophosphamide

2-Anthracene amide

Cyclophosphamide

2-Anthracene amide

Concentration µg/plate

 

2

1500

2

1500

2

 

M

524.3

1190.7

1233.7

432.3

285.3

 

±SD

39.8

73.5

92.2

20.0

52.3

Conclusions:
Interpretation of results:
negative with and without metabolic activation

In a bacterial mutagenicity assay according to OECD 471 and GLP, no mutagenic effect (no increase in revertant colony numbers as compared with control counts) was observed for the test substance tested up to a concentration of 1000 µg/plate in any of the five test strains in two independent experiments without and with metabolic activation (plate incorporation or preincubation test).
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08-11-2007 To 22-12-2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Target gene:
Not applicable.
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.
Test concentrations with justification for top dose:
Toxicity test: +S9 : 9.34, 18.75, 37.5, 75, 150, 300, 600 and 1203 µg/ml
Toxicity test: -S9: 75, 150, 300, 600 and 1203 µg/ml
Cytogenetic analysis:
4 and 20 hours treatment without S9 mix - 300, 600 and 1203 µg/ml
4 Hours treatment with S9 mix - 37.5, 75 and 150 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone.
- Justification for choice of solvent/vehicle: Acetone was used as the solvent based on the solubility of the test article and compatibility with the target cells.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
+ S9: at final concentrations of 10 and 20 µg/ml.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
-S9: at final concentrations of 0.1 and 0.2 µg/ml.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium.

DURATION
- Exposure duration: In the non-activated study, the cells were exposed to the test article for 4 hours or continuously for 20 hours. In the S9-activated study, the cells were exposed for 4 hours.
- Expression time (cells in growth medium): 16 hours for the 4 hours non-activated and activated cells.
- Fixation time (start of exposure up to fixation or harvest of cells): 20 hours

SPINDLE INHIBITOR (cytogenetic assays): Two hours prior to the scheduled cell harvest, Colcemid was added to duplicate flasks for each treatment condition at a final concentration of 0.1 µg/ml and the flasks returned to the incubator until cell collection.
STAIN (for cytogenetic assays): The dried slides were stained with 5% Giesma, air dried and permanently mounted.

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED: A minimum of 200 metaphase spreads (100 per duplicate flask) were examined and scored for chromatid-type and chromosome aberrations.

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative total growth.

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes
- Other: Chromatid-type aberrations include chromatid and isochromatid breaks and exchange figures as quadriradials (symmetrical and asymmetrical interchange), triradicals, and complex rearrangements. Chromosome-type aberrations include chromosome breaks and exchange figures such as dicentrics and rings. Fragments (chromatids or acentric) observed in the absence of any exchange figure were scored as a break (chromatid or chromosome). Fragments observed with an exchange figure were not scored as an aberration but instead were considered part of the incomplete exchange. Pulverised chromosome(s), pulverised cells and severely damaged cells (≥aberrations) were also recorded. Chromatid gaps and isochromatids gaps were recorded but not included in the analysis. The XY coordinates for each cell with chromosomal aberrations were recorded using the microscopic stage.

METABOLIC ACTIVATION SYSTEM: Aroclor 1254-induced rat liver S9 was used as the metabolic activation system. The S9 mix was mixed with a cofactor pool containing:
- 2 mM magnesium chloride
- 6 mM potassium chloride
- 1 mM glucose-6-phosphate
- 1 mM nicotinamide adenine dinucleotide phosphate (NADP)
- 20 µL S9 per ml medium (McCoy's 5A serum-free medium supplemented with 100 units penicillin/ml, 100 µg stretomycin/ml, 2mM L- glutamine and 2.5 µg/ml amphotericin B).
Evaluation criteria:
The toxic effects of treatment were based upon cell growth inhibition relative to the solvent-treated control. The number and types of aberrations found the percentage of structurally and numerically damaged cells (percent aberrant cells) in the total population of cells examined, and the mean aberrations per cell were calculated and reported for each treatment group. Chromatid and isochromatid gaps do not include the total percentage of cells with one or more aberrations or in the frequency of structural aberrations per cell.
Statistics:
Statistical analysis of the percent aberrant cells was performed using the Fisher’s Exact test. Fisher’s Exact test was used to compare pairwise the percent aberrant cells of each treatment group with that of the solvent control. In the event of a positive Fishers’s Exact test at any test article dose level, the Cochran-Armitage test was used to measure dose-responsiveness. All conclusions were based on sound scientific basis; however, as a guide to interpretation of the data, the test article was considered to induce a positive response when the percentage of cells with aberrations is increased in a dose-responsive manner with one or more concentrations being statistically significant (p≤0.05). However, values that are statistically significant but do not exceed the range of historical solvent may be judged as not biologically significant. Test articles not demonstrating a statistically significant increase in aberrations will be concluded to be negative.
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: The pH of the highest concentration of test article in treatment medium was approximately 7.0.
- Effects of osmolality: In the preliminary toxicity assay the osmolality in treatment medium of the highest concentration tested, 1203 µg/ml, was 291 mmol/kg. The osmolality of the solvent (acetone) in treatment medium was 290 mmol/kg. The osmolality of the test article concentration in treatment medium is acceptable because it did not exceed the osmolality of the solvent by more than 20%.
- Water solubility: The test article was soluble in actone at a concentration of approximately 500 mg/ml, the maximum concentration tested for solubility.

RANGE-FINDING/SCREENING STUDIES: In the preliminary toxicity assay, substantial toxicity (i.e., at least 50% cell growth inhibition, relative to the solvent control) was not observed at any dose level in the non-activated 4 and 20-hour exposure groups. Substantial toxicity was observed at doses ≥360.9 µg/mL in the S9-activated 4-hour exposure group. Based upon the results of the toxicity study, the dose level for the chromosome aberration assay was selected.


COMPARISON WITH HISTORICAL CONTROL DATA:

The percent aberrant cells in the test article-treated groups were within the historical solvent control range

ADDITIONAL INFORMATION ON CYTOTOXICITY:
Toxicity of Dimethoxydimethylsilane (cell growth inhibition relative to the solvent) in CHO cells when treated for 4 hours in the absence of S9 activation was 14% at 1203 µg/ml, the highest test concentration evaluated for chromosome aberration. The mitotic index at the highest dose level evaluated for chromosome aberration, 1203 µg/ml, was 10% reduced relative to the solvent control. The percentage of cells with structural or numerical aberrations in the test article- treated group was not significantly increased relative to solvent control at any dose level (p≥0.05, Fisher Exact test). The percentage of structurally damaged cells in the MMC (positive control) treatment group (22%) was statistically significant.
Toxicity of Dimethoxydimethylsilane (cell growth inhibition relative to the solvent) in CHO cells when treated for 4 hours in the presence of S9 activation was 54% at 150 µg/ml, the highest test concentration evaluated for chromosome aberrations. The mitotic index at the highest dose level evaluated for chromosome aberrations, 150 µg/mL, was 27% reduced relative to the solvent control. The percentages of cells selected for microscopic analysis were 37.5, 75 and 150 µg/ml. The percentage of cells with structural or numerical aberrations in the test article-treated group was not significantly increased relative to solvent control at any dose level (p≥0.05, Fisher’s Exact test). The percentage of structurally damaged cells in the CP (positive control) treatment group (23.0%) was statistically significant.
Toxicity of Dimethoxydimethylsilane (cell growth inhibition relative to the solvent) in CHO cells when treated for 20 hours in the absence of S9 activation was 14% at 1203 µg/ml, the highest test concentration evaluated for chromosome aberrations in the non-activated 20-hour continuous exposure group. The mitotic index at the highest dose level evaluated for chromosome aberrations, 1203 µg/ml, was 29% reduced relative to the solvent control. The dose level selected for microscopic analysis was 300, 600 and 1203 µg/ml. The percentage of cells with structural or numerical aberrations in the test article-treated group was not significantly increased relative to solvent control at any dose level (p≥0.05, Fisher’s Exact test).The percentage of structurally damaged cells in the MMC (positive control) treatment group (22.0%) was statistically significant.

Table 1: Summary

Treatment

µg/mL

S9 Activation

Treatment time

Mean Mitotic index

Cells scored

Aberrations per cells

Cells with Aberrations

Numerical

Structural

(Mean ± SD)

Numerical %

Structural %

Acetone

-S9

4

7.1

200

200

0.000

±0.00

1.5

0.0

Dimethoxydimethylsilane

300

-S9

4

8.6

200

200

0.000

±0.000

2.0

0.0

600

S9

4

7.3

200

200

0.015

±0.122

2.0

1.5

1203

S9

4

6.4

200

200

0.010

±0.100

2.5

1.0

MMC -0.2

S9

4

6.6

200

50

0.280

±0.573

2.0

22.0**

Acetone

+S9

4

9.4

200

200

0.025

±0.186

3.0

2.0

Dimethoxydimethylsilane

37.5

+S9

4

8.6

200

200

0.010

±0.100

4.5

1.0

75

+S9

4

8.6

200

200

0.020

±0.140

5.0

2.0

150

+S9

4

6.9

200

200

0.035

±0.232

4.5

2.5

CP- 10.0

+S9

4

4.8

200

100

0.350

±0.744

4.0

23.0**

Acetone

-S9

20

10.0

200

200

0.000

±0.000

1.5

0.0

Dimethoxydimethylsilane

300

-S9

20

8.2

200

200

0.000

±0.000

2.5

0.0

600

-S9

20

6.8

200

200

0.000

±0.000

3.5

0.0

1203

-S9

20

7.1

200

200

0.010

±0.100

3.0

1.0

MMC- 0.1

-S9

20

6.2

200

50

0.260

±0.565

1.5

22.0**

Treatment: Cells from all treatment conditions were harvested 20 hours after the initiation of the treatments.

Aberrations per cells: Severely damaged cells were counted as 10 aberrations.

Percent Aberration Cells: *, p0.05; **, p0.01; using Fishers’s Exact test.

Conclusions:
Interpretation of results:
negative with and without metabolic activation.

In an in vitro cytogenicity test according to OECD 473 and to GLP, the test substance, dimethoxydimethylsilane was concluded to be negative for the induction of structural and numerical chromosome aberrations in CHO cells in both the non-activated and the S9-activated systems.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment.

A key bacterial reverse mutation assay conducted in compliance with GLP and according to OECD TG 471 is available for dimethoxydimethylsilane.  No evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA102. The strains were treated with doses up to a concentration of 1000 µg/plate in two independent experiments without and with metabolic activation (plate incorporation or preincubation test). Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, dimethoxydimethylsilane was concluded to be non-mutagenic in the Salmonella typhimurium strains (Laboratory of Pharmacology and Toxicology KG, 2003).

The key in vitro cytogenicity study on dimethoxydimethylsilane was conducted according to OECD TG 473 and to GLP. The test substance did not cause a statistically significant, dose related increase in chromosome aberrations in Chinese hamster ovary CHO) cells with or without metabolic activation. Appropriate positive and solvent controls were included and gave expected results. The test substance was therefore considered non-clastogenic in Chinese hamster ovary CHO cells (Dow Corning Corporation, 2008b).

A mammalian cell gene mutation study is not avaiable yet. This information will be submitted later based on ECHA decision number CCH-D-2114428794-40-01/F.

Justification for classification or non-classification

The available in vitro data on mutagenicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification of the registered substance.