Registration Dossier

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 activation in Salmonella typhimurium strains: TA 98, TA 100, TA 1535, and TA 1537 (similar to OECD TG 471).

Mammalian cytogenicity (Chinese hamster lung fibroblasts V79 cell chromosome aberration assay): negative with and without metabolic activation (according to OECD TG 473).

Mammalian cell gene mutation:

No measured data are available to assess the in vitro mammalian mutagenicity potential of the registered substance, however, reliable data are available for the structural analogue substance trichloro(phenyl)silane (CAS: 98-13-5).

negative in L5178Y mouse lymphoma cells with the structural analogue substance trichloro(phenyl)silane (CAS: 98 -13 -5) (according to OECD TG 476).

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:
30-04-1994 To 14-11-1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
the range of strains does not comply with the current guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Did not include strain to detect cross-linking mutagens.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
His operon
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 (TA98 & 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:
8-5000 µg/plate - Plate incorporation method.
31.25-1200 µg/plate - Pre-incubation method.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethylene glycol dimethylether (EGDE, dryed with a molcular sieve, 0.4 nm)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: nitrofurantoin
Remarks:
-S9: TA 100: 0.2 µg per plate.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
-S9: TA 1535: 10 µg per plate.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: phenylene diamine
Remarks:
-S9: TA1537 and TA98 : 10 and 0.5 µg per plate, respectively.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
+ S9: All strains: 3 µg per plate.
Details on test system and experimental conditions:
METHOD OF APPLICATION:in agar (plate incorporation) and preincubation;

DURATION
- Preincubation period: 30 minutes
- Exposure duration: 48 hours


NUMBER OF REPLICATIONS: 4

DETERMINATION OF CYTOTOXICITY
- Method: Gross appraisal of background growth on the plate, marked or dose-dependent reduction in the mutant count per plate and the titer was determined.


Metabolic activation system: It was made from the livers of at least six adult male Sprague-Dawley rats, of approximately 200 to 300 g in weight. For enzyme induction, the animals received a single intraperitoneal injection of Aroclor 1254, dissolved in corn oil, at a dose of 500 mg/kg bw, five days prior to sacrifice. The S9 mix also contained seventy mL of cofactor solution containing the following:

-MgCl2 x 6H2O (162.6 mg)
-KCl (246.0 mg)
-Glucose-6-phophate, disodium salt (179.1 mg)
NADP, disodium salt (315.0 mg)
-Phosphate buffer (100.0 mg)

Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas TA 1537, at least a threefold increase should be reached. However, these guidelines may be overruled by good scientific judgement.
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>62.5 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY: The salmonella/ microsome plate incorporation test, employing doses of up to 5000 µg per plate, showed diphenyldichlorosilane to produce bacterial toxic effects at 40 µg per plate and above. Therefore, 5000 µg per plate could not be used for assessment. The salmonella/ microsome test, using preincubation for 30 minutes at 37 °C and employing doses of up to 1200 µg per tube, showed diphenyldichlorosilane to produce bacterial toxic effects at 100 µg per tube and above.

Table 1. Summary of mean values without S9 mix.

Groups

Strain

TA 1535

TA 100

TA 1537

TA 98

Plate incorporation method (µg/plate)

 

 

 

 

0

25

120

12

23

8

26

116

9

24

40

27

117

11

24

20

31

104

9

23

1000

30

105

8

29

5000

-

-

-

-

Na-azide

926

 

 

 

NF

 

378

 

 

4-NPDA

 

 

101

118

Pre-incubation method- µg/plate

 

 

 

 

0

22

143

13

31

31.25

29

146

13

31

62.5

36

157

14

31

125

30

166

15

28

250

43

134

8

27

500

38

144

6

22

1000

32

117

6

17

Na-azide

897

 

 

 

NF

 

531

 

 

4-NPDA

 

 

83

60

Table 2. Summary of mean values with S9 mix.

Groups

Strain

TA 1535

TA 100

TA 1537

TA 98

Plate incorporation method (µg/plate)

 

 

 

 

0

21

150

16

42

8

19

146

12

44

40

18

142

14

42

20

17

119

12

39

1000

16

119

12

34

5000

-

-

-

-

2-AA

211

1476

117

891

Pre-incubation method (µg/plate)

 

 

 

 

0

17

141

10

40

31.25

17

151

12

38

62.5

17

148

13

46

125

22

166

11

45

250

19

154

11

48

500

21

168

11

41

1000

19

119

7

36

2-AA

213

1268

126

1107

Plate incorporation method:

There was no indication of a bacterial toxic effect of diphenylchlorosilane at 8 µg per plate. The total bacterial counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. None of the four strains concerned showed a dose- related and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9-mix.

 Pre-incubation method:

There was no indication of a bacterial toxic effect of diphenylchlorosilane at doses of up to and including 62.5 µg per tube. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. One of the four strains concerned revealed an increase in mutant counts to double those of negative controls. Strains TA 1535 were affected. This increase did, however, not correlate with dose and could not be confirmed. Therefore, it was considered to be of no relevance.

The positive controls sodium azide, nitrofurantonin, 4-nitro-1,2-phenyl diamine and 2-aminoanthracene increased mutant counts well over those of the negative controls, and thus demonstrated the system’s sensitivity and the activity of the S9 mix

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

In a bacterial mutagenicity assay according to OECD 471 and GLP, no indications of mutagenic effects of diphenyldichlorosilane was found at assessable doses of up to 1200 µg per plate in any of the Salmonella typhimurium strains used in the plate incorporation assay and in the preincubation assay.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03-05-1985 to 06-05-1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Plate incorporaton only, apparently no replicates
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
plate incorporaton only, apparently no replicates
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
His operon
Species / strain / cell type:
E. coli WP2
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
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:
0.078-1.25 µg/plate
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:
other: 2-Anthramine and 2-Aminofluorene
Remarks:
+S9: All strains: 10 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 9-Amino acridine, Sodium azide, Daunomycin, 4-Nitroquinoline-N-Oxide and N-Mehtyl-N-nitro-N-nitrosoquanidine
Remarks:
-S9: All strains: 10 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation).

DURATION
- Exposure duration: 72 hours


NUMBER OF REPLICATIONS:1


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth.


Evaluation criteria:
Not reported
Statistics:
Not reported
Species / strain:
E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
1.25 µg/plate
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, TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
1.25 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY: Concentrations of test material above 1.25 µg/plate were toxic to the tester strains.

Table 1. Overlay plate test results:

Test

Revertants per plate

TA-1535

TA-1537

TA-98

TA-100

WP2

Non-Activation (-S9)

 

 

 

 

 

Solvent control

29

9

22

94

36

Positive control*

125

152

169

532

124

Test Material (µg/plate)

 

 

 

 

 

0.078

23

10

19

98

42

0.156

22

7

18

126

37

0.312

17

6

16

84

37

0.625

11

8

22

120

28

1.250

14

9

24

132

24

Activation (+S9)

 

 

 

 

 

Solvent control

17

8

58

100

17

Positive control**

171

168

1074

1045

251

Test Material (µg/plate)

 

 

 

 

 

0.078

13

12

49

98

18

0.156

15

8

58

94

17

0.312

16

12

51

114

19

0.625

12

12

50

121

17

1.250

13

14

43

88

20

*TA-1535: AZ (10 µg/plate)         ** TA-1535:ANTH (10 µg/plate)         

*TA1537: NQNO (10 µg/plate)      ** TA1537:AF(10 µg/plate)         

*TA98: D (10 µg/plate)                   ** TA98:AF (10 µg/plate)         

*TA-100: AZ (10 µg/plate)             **TA-100:AF (10 µg/plate)         

*WP2:MNNG (10 µg/plate)           **WP2:ANTH (10 µg/plate)        

Solvent: Dimethylsulfoxide (50 µg/plate)         

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

In a bacterial mutagenicity assay according to OECD 471 and GLP, the test material failed to exhibit mutagenic activity in both the activation and non-activation systems and is considered not to be mutagenic under the conditions employed.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-07-20 to 2011-12-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
- Type and identity of media: MEM
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 of Wistar phenobarbital and ß-naphthoflavone-induced rat liver S9 mix
Test concentrations with justification for top dose:
Pre-experiment:
with and without metabolic activation:
0.020, 0.039, 0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5 and 10 mM

Experiment I:
without metabolic activation:
0.7, 0.9 and 1.1 mM

with metabolic activation:
0.625, 1.25 and 2.5 mM

Experiment II:
without metabolic activation:
0.30, 0.45 and 0.60 mM

with metabolic activation:
1.5, 2.0 and 2.5 mM
Vehicle / solvent:
-Vehicle (s)/solvent(s) used: cell culture medium (MEM)
- Justification for choice of solvent/vehicle: Due to the nature of the test item it was suspended in cell culture medium (MEM). The solvent was compatible with the survival of the cells and the S9 activity.
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation Migrated to IUCLID6: 400 and 600 µg/mL
Positive control substance:
cyclophosphamide
Remarks:
with metabolic activation Migrated to IUCLID6: 0.83 µg/mL
Details on test system and experimental conditions:
TREATMENT TIME:
4 hours (Experiment I with and without metabolic activation, experiment II with metabolic activation)
20 hours (Experiment II without metabolic activation)

FIXATION INTERVAL: 20 hours (Experiment I and II with and without metabolic activation)
NUMBER OF REPLICATIONS: 2 independent experiments
NUMBER OF CELLS SEEDED: 1 x 10^4 - 5 x 10^4 cells
NUMBER OF CULTURES: two cultures per concentration
NUMBER OF CELLS SCORED: 200 cells per concentration (100 cells per culture),
except for concentration 2.5 mM (experiment II with metabolic activation): 112 for the 1st and 100 for the 2nd culture.
DETERMINATION OF CYTOTOXICITY: Mitotic index, cell density
Evaluation criteria:
There are several criteria for determining a positive result:
- a clear and dose-related increase in the number of cells with aberrations,
- a biologically relevant response for at least one of the dose groups, which is higher than the laboratory negative control range (0.0% - 4.0% aberrant cells (with and without metabolic activation)).


Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid

Results of chromosome analysis
without metabolic activation
     Cytotoxicity Chromatid aberrations         Isochromatid aberrations       rel. Mitotic index (%) rel. Cell density (%)  Poly-ploidy mean % aberrant cells
Scored cells  gaps breaks  inter-changes  other  gaps breaks  inter-changes  other incl. Gaps excl. Gaps
 Experiment I                              
negative control 200 - 2 1 1 1 0 0 1 0 100 100 0 2.5 1.5
0.25 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 122 n.d. n.d. n.d. n.d.
0.5 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 106 n.d. n.d. n.d. n.d.
0.7 mM 200 no 3 1 0 0 0 0 0 0 104 93 1 2.0 0.5
0.9 mM 200 no 2 0 0 1 0 0 0 0 73 75 0 1.5 0.5
1.1 mM 200 yes  6 2 0 1 0 0 1 0 47 66 1 4.0 1.5
1.3 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 0 n.d. n.d. n.d. n.d.
1.5 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 0 n.d. n.d. n.d. n.d.
EMS (600 mg/mL) 200 - 5 11 5 3 0 0 1 0 101 91 0 11.0 9.0
 Experiment II                                  
negative control 200 - 1 0 0 0 0 0 2 0 100 100 0 1.5 1.0
0.10 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 97 n.d. n.d. n.d. n.d.
0.30 mM 200 no 2 3 0 0 1 0 0 0 83 98 1 3.0 1.5
0.45 mM 200 no 2 0 1 0 0 0 1 0 71 98 0 2.0 1.0
0.60 mM 200 yes 0 2 0 1 1 0 1 0 44 85 1 2.5 2.0
0.75 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 0 n.d. n.d. n.d. n.d.
EMS (400 µg/mL) 200 - 0 12 5 0 1 0 1 1 54 98 1 8.5 8.0
Results of chromosome analysis
with metabolic activation
     Cytotoxicity Chromatid aberrations         Isochromatid aberrations       rel. Mitotic index (%) rel. Cell density (%)  Poly-ploidy mean % aberrant cells
Scored cells  gaps breaks  inter-changes  other  gaps breaks  inter-changes  other incl. Gaps excl. Gaps
 Experiment I                              
negative control 200 - 6 3 0 0 0 0 0 0 100 100 5 4.5 1.5
0.156 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 96 n.d. n.d. n.d. n.d.
0.313 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 92 n.d. n.d. n.d. n.d.
0.625 mM 200 no 4 1 0 1 1 0 0 0 92 109 0 3.5 1.0
1.25 mM 200 no 1 3 0 0 1 0 0 0 104 94 0 2.5 1.5
2.5 mM 200 yes 3 3 0 0 0 0 0 0 47 97 1 3.0 2.0
5 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
10 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d.
CPA (0.83 µg/mL) 200 - 7 10 3 4 0 0 0 0 82 87 1 11.5 8.5
 Experiment II                                  
negative control 200 - 4 2 0 0 0 0 0 0 100 100 1 3.0 1.0
0.75 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 95 n.d. n.d. n.d. n.d.
1.0 mM - no n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 91 n.d. n.d. n.d. n.d.
1.5 mM 200 no 3 1 0 0 0 0 0 0 87 110 1 2.0 0.5
2.0 mM 200 yes 2 3 0 0 0 0 1 0 41 111 2 3.0 2.0
2.5 mM 212 yes 3 4 0 2 0 0 0 0 32 45 1 4.2 2.8
3.0 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 10 n.d. n.d. n.d. n.d.
3.5 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 15 n.d. n.d. n.d. n.d.
4.0 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 0 n.d. n.d. n.d. n.d.
5.0 mM - yes n.d. n.d. n.d. n.d. n.d. n.d. n.d. n.d. 0 n.d. n.d. n.d. n.d.
CPA (0.83 µg/mL) 200 - 12 13 5 1 0 0 0 0 88 104 1 11.5 8.0

n.d. not determined

 

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

In conclusion, it can be stated that during the described in vitro chromosomal aberration test and under the experimental conditions reported, the test item Dichloro(diphenyl)silane did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line.
Therefore, the test item Dichloro(diphenyl)silane is considered to be non-clastogenic in this chromosome aberration test.
Executive summary:

To investigate the potential of Dichloro(diphenyl)silane to induce structural chromosome aberrations in Chinese hamster V79 cells, anin vitrochromosome aberration assay was carried out.

The chromosomes were prepared 20 h after start of treatment with the test item. The treatment interval was 4 h with and without metabolic activation in experiment I. In experiment II, the treatment interval was 4 h with and 20 h without metabolic activation. Duplicate cultures were treated at each concentration. 100 metaphases per culture were scored for structural chromosomal aberrations (except for concentration 2.5 mM (experiment II with metabolic activation): 112 for the 1st and 100 for the 2nd culture.)

Due to the nature of the test item it was suspended in cell culture medium (MEM). The solvent was compatible with the survival of the cells and the S9 activity.

The following concentrations were evaluated for the microscopic analysis of chromosomal aberrations:

Experiment I:

without metabolic activation: 0.7, 0.9 and 1.1 mM

with metabolic activation: 0.625, 1.25 and 2.5 mM

Experiment II:

without metabolic activation: 0.30, 0.45 and 0.60 mM

with metabolic activation: 1.5, 2.0 and 2.5 mM

In the experiments without metabolic activation no precipitation of the test item was noted after incubation with the test item at the concentrations evaluated, with metabolic activation precipitation of the test item was noted at a concentration of 2.5 mM in experiment I and 1.5 mM in experiment II.

In experiment I without metabolic activation, toxic effects of the test item were noted at a concentration of 1.1 mM, with metabolic activation at a concentration of 2.5 mM.

In experiment II without metabolic activation, toxic effects of the test item were observed at a concentration of 0.60 mM. With metabolic activation toxic effects of the test item were noted at concentrations of 2.0 mM and higher.

In experiment I and II no biologically relevant increase of the aberration rates was noted after treatment with the test item with and without metabolic activation. The aberration rates of all dose groups treated with the test item were within the historical control data of the negative control.

In both experiments with and without metabolic activation no biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item as compared to the controls.

EMS (400 and 600 µg/mL) and CPA (0.83 µg/mL) were used as positive controls and induced distinct and biologically relevant increases in cells with structural chromosomal aberrations.

The positive controls induced the appropriate responses.

There was no evidence of test item induced over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OPPTS 870.5375; OECD 473 for in vitro cytogenetic mutagenicity data. 

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
900 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative with and without activation

The structural analogue substance trichloro(phenyl)silane (CAS: 98-13-5) was tested in a reliable study according to OECD TG 476 and under GLP. No increase in mutant frequency was observed at any concentration with and without activation (4 hours treatment) and without activation (24 hours treatment). Expected results were obtained with positive and negative controls. It is concluded that trichloro(phenyl)silane and thus dichloro(diphenyl)silane are negative for the induction of mutations in L5178Y cells under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A key bacterial reverse mutation assay according to OECD TG 471 and GLP is available for dichloro(diphenyl)silane. No evidence for a test-substance related increase in the number of revertants was observed in Salmonella typhimurium strains: TA 98, TA 100, TA 1535, and TA 1537. The strains were treated with doses of up to 1200 µg/plate with and without metabolic activation system. Appropriate positive and solvent controls were included and gave expected results. Under the conditions of this study, dichloro(diphenyl)silane was concluded to be non-mutagenic in the Salmonella typhimurium strains tested (Herbold, B.1994). An additional key bacterial reverse mutation assay with the registered substance is also available. In that study, there was 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 Escherichia coli WP2 strains.  The strains were treated with doses of 0.078 to 1.25 µg/plate with and without metabolic activation system. Appropriate positive and solvent controls were included and gave expected results ( Dow Corning Corporation, 1985). The results of both studies are in agreement and give evidence that the test substance is non-mutagenic in the bacterial reverse mutation assay under the applied test conditions.

 

The key in vitro cytogenicity study on dichloro(diphenyl)silane was conducted according to OECD TG 473 and to GLP. In the presence and absence of metabolic activation no biologically relevant increase in the frequencies of polyploidy cells was found after treatment with the test item in Chinese Hamster V79 cells as compared to the controls. Appropriate positive and solvent controls were included and gave expected results. The test substance was therefore considered to be non-clastogenic in Chinese Hamster V79 cells (Oppong-Nketiah, M. 2012).

 

The key in vitro mammalian cell gene mutation study on the structural analogue substance trichlorophenylsilane (CAS: 98-13-5) was conducted according to OECD TG 476 and to GLP. No increase in mutant frequency was observed at any concentration with and without metabolic activation after 4 hours of treatment and without metabolic activation after 24 hours of treatment. Expected results were obtained with positive and negative controls. It was concluded that the structural analogue substance, trichlorophenylsilane is negative for the induction of mutations in L5178Y cells under the conditions of the test (Flanders, L.2010).

 

In vivo testing is not required as no evidence for genetic toxicity was found in the in vitro studies.

 

 

Justification for classification or non-classification

 Based on the available in vitro data on mutagenicity of the registered substance and the structural analogue substance, trichloro(phenyl)silane (CAS: 98-13-5, dichloro(diphenyl)silane is not classified for mutagenicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.