Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation in bacteria: Weight of evidence: Based on read-across approach the experimental data on analogue butanone oxime (test methods similar to OECD 471), butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be negative for genetic toxicity in vitro.

In vitro cytogenicity in mammalian cells: Key studies: Based on read-across approach the experimental data on analogue butanone oxime (test method similar to OECD 473), butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be negative against chromosomal aberrations with and without S9.

In vitro gene mutation study in mammalian cells: Key study: Based on read-across approach the experimental data on analogue butanone oxime where mutagenicity was observed only in presence of cytotoxicity and without metabolic activation, there cannot be concluded that butan-2-one O,O',O''-(vinylsilanetriyl)oxime induces gene mutation in mammalian cells.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
A standard NTP (National Toxicology Program) protocol
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(4 strain were tested)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: TA97, TA98, TA100, TA1535
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver)
Test concentrations with justification for top dose:
TA1535: 0, 100, 333, 1000, 3333, 5000, 6667, 10000 µg/plate.
TA97, TA98: 0, 100, 333, 1000, 3333, 10000 µg/plate.
TA100: 0, 100, 333, 500, 10000, 3333, 5000, 6667, 7500, 10000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide
Negative solvent / vehicle controls:
yes
Remarks:
(Dimethyl Sulfoxide)
Positive controls:
yes
Positive control substance:
sodium azide
Positive controls:
yes
Positive control substance:
9-aminoacridine
Positive controls:
yes
Positive control substance:
other: 4-nitro-o- phenylenediamine (TA98. without metabolic activation)
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene (TA100, TA1535, TA97 and TA98. with metabolic activation)
Details on test system and experimental conditions:
METHOD OF APPLICATION: Preincubation. Test tube containing a suspension of one strain of Salmonella typhimurium plus S9 mix or plain buffer without S9, is incubated for 20 minutes at 37º C with the test chemical. Control cultures, with all the same ingredients except the test chemical, are also incubated. In addition, positive control cultures are prepared; these contain the particular bacterial tester strain and a known potent mutagen. After 20 minutes, agar is added to the cultures and the contents of the tubes are thoroughly mixed and poured onto the surface of Petri dishes containing standard bacterial culture medium. The plates are incubated, and bacterial colonies that do not require an excess of supplemental histidine appear and grow. These colonies are comprised of bacteria that have undergone reverse mutation to restore function of the histidine -manufacturing gene. The number of colonies is usually counted after 2 days.

SELECTION AGENT (mutation assays): Top agar supplemented with L-histidine and d-biotin

NUMBER OF REPLICATIONS: 3 replicates per trial.

Evaluation criteria:
A positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following chemical treatment. There was no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.
Key result
Species / strain:
other: TA97, TA98, TA100, TA1535
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
(at strain 1535 with induced male Syrian hamster liver S9)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No
- Contamination: No

Results on strain TA100, TA1535, TA97 and TA98 with and without metabolic activation:

Strain: TA100

Dose

No Act.

No Act.

No Act.

30% HLI

30% HLI

30% HLI

30% HLI

30% RLI

30% RLI

(Negative)

(Negative)

(Negative)

(Negative)

(Equivocal)

(Not Valid)

(Negative)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

µg/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

97

0.9

93

1.5

88

0.3

123

1.2

107

4

118

2.8

124

3.8

123

12.3

132

2.3

100

97

0.9

 

 

 

 

99

5.8

 

 

 

 

 

 

111

3.8

 

 

333

92

3.8

 

 

89

0.9

118

12.4

 

 

 

 

 

 

110

3.4

 

 

500

 

 

 

 

 

 

 

 

 

 

 

 

134

6.7

 

 

 

 

1000

81

2.3

84

6.4

108

4.1

120

10.3

121

6

146

2

122

10.4

95

8.7

114

10.3

3333

52

4.1

83

6.1

87

7.2

118

5.4

123

0.7

175

5.5

144

6

80

6.1

113

6.7

5000

 

 

82

6.3

76

9.2

 

 

163

18.2

160

6.4

 

 

 

 

111

2.2

6667

 

 

15

5

20

5.9

 

 

172

4.1

146

26

121c

19.5

 

 

85

4.9

7500

 

 

 

 

 

 

 

 

 

 

112

2.7

131

5.6

 

 

 

 

10000

0

0

15

7.2

 

 

62

12.5

127

9.1

 

 

 

 

6

6.3

6

2

Positive Control

257

11.6

745

28.2

524

37.7

475

28

769

30.6

205

4.6

519

0.7

1199c

115.5

581

55.8

Strain: TA1535

Dose

No Act.

30% HLI

30% HLI

30% RLI

30% RLI

(Negative)

(Positive)

(Positive)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

µg/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

13

1.7

15

0.6

8

2.6

7

1.2

16

3.2

100

13

2.7

10

0.3

 

 

7

1

 

 

333

18

2.3

10

0.6

 

 

9

1.5

 

 

1000

16

2.6

20

2.8

26

3.1

16

2.7

15

1.8

3333

14

3.5

35

1.2

54

2.4

8

1

17

2.3

5000

 

 

 

 

76

3.8

 

 

11

1.2

6667

 

 

 

 

98

11.6

 

 

17

2.3

10000

9

1.5

70

7.8

87

6.4

4

1.2

3

0.3

Positive Control

181

9.5

81

3.5

109

9.2

89

8.5

137

8.1

Strain: TA97

Dose

No Act.

30% HLI

30% RLI

(Negative)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

µg/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

135

11

160

14.3

148

3.1

100

115

4.2

165

7.3

142

1

333

129

4

152

3.5

155

5

1000

103

10.2

165

3.9

147

2.7

3333

95

9.5

143

3.2

126

21.3

10000

60

3.2

154

7.7

105

1.2

Positive Control

356

15.6

1139

7.5

672

24

Strain: TA98

Dose

No Act.

No Act.

30% HLI

30% HLI

30% RLI

30% RLI

(Not Valid)

(Negative)

(Not Valid)

(Negative)

(Not Valid)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

µg/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

857

14.7

17

2.4

638

23.4

33

2.5

766

32.9

33

3

100

 

 

22

1.8

 

 

38

7

 

 

28

3.7

333

 

 

24

4.7

 

 

30

1.2

 

 

28

4.4

1000

 

 

18

4.7

 

 

35

0.3

 

 

28

3

3333

 

 

19

0.6

 

 

38

3.8

 

 

22

2.6

10000

 

 

4

2

 

 

17

3.1

 

 

13

2.2

Positive Control

 

 

405

5

 

 

84

4.7

 

 

291

6.1

Abbreviations:

RLI = induced male Sprague Dawley rat liver S9

HLI = induced male Syrian hamster liver S9

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Conclusions:
No mutagenic responses were observed in strains TA97, TA98, or TA100 with and without S9. Over a concentration range of 100 to 10000 μg/plate, was mutagenic in Salmonella typhimurium strain TA1535 in the presence of induced hamster liver S9 but no increase in revertant colonies was observed in strain TA1535 treated in the presence of induced rat liver S9 or without exogenous metabolic activation.
Executive summary:

A Salmonella typhimurium mutagenicity test was performed on methyl ethyl ketoxime according to NTP's preincubation protocol (test method similar to OECD Guideline 471). The Salmonella typhimurium strains TA97, TA98, TA100 and TA1535 in either with metabolic activation (S9 mix from Aroclor 1254-induced male Sprague-Dawley rat and Syrian hamster liver) and without metabolic activation were exposed up to 10000 µg/plate test item. Negative and positive controls were performed satisfactorily. No mutagenic responses were observed in strains TA97, TA98, or TA100 with and without S9. Methyl ethyl ketoxime, over a concentration range of 100 to 10000 μg/plate, was mutagenic in Salmonella typhimurium strain TA1535 in the presence of induced hamster liver S9 but no increase in revertant colonies was observed in strain TA1535 treated in the presence of induced rat liver S9 or without exogenous metabolic activation. Therefore, methyl ethyl ketoxime was at most weakly genotoxic since it induced mutations under very specific conditions.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
A standard NTP (National Toxicology Program) protocol. Only 2 strains were tested.
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(only 2 strains were tested)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: TA98, TA100
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver)
Test concentrations with justification for top dose:
0 (control), 0.005, 0.007, 0.01, 0.025, 0.05, 0.1, 0.5, 1 mL/chamber.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide
Negative solvent / vehicle controls:
yes
Remarks:
(Dimethyl Sulfoxide)
Positive controls:
yes
Positive control substance:
sodium azide
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-pehnyelenediamine
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: Plate tests conducted within a sealed dessicator (gas chamber) for exposure to gaseous substances. The lids of the plates were removed and the plates were stacked on a perforated porcelain plate in a 9-liter desiccator jar containing a magnetic stirring bar. A measured volume (4.0 mL) of methyl ethyl ketoxime was introduced into a glass petri dish suspended below the porcelain plate. The desiccator was sealed and placed on a magnetic stirrer in a 37 ºC incubator. After 24 hours the plates were removed from the desiccator and incubated at 37 ºC, in air, for an additional 24 hours. The dose was expressed as mL methyl ethyl ketoxime per chamber.

SELECTION AGENT (mutation assays): L-histidine

NUMBER OF REPLICATIONS: 3 replicates per trial.
Evaluation criteria:
A positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following chemical treatment. There was no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.
Key result
Species / strain:
other: TA98, TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to 1 mL/chamber)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No.
- Contamination: No.

Results on strain TA100 with and without metabolic activation:

Strain: TA100

Dose

No Act.

No Act.

No Act.

No Act.

30% HLI

30% HLI

30% HLI

30% HLI

30% RLI

30% RLI

30% RLI

30% RLI

(Negative)

(Not Valid)

(Negative)

(Not Valid)

(Negative)

(Not Valid)

(Negative)

(Not Valid)

(Negative)

(Not Valid)

(Negative)

(Not Valid)

Protocol

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

Plate Test - Vapor

mL / chamber

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0

75

1.7

76

2.6

121

2.7

166

6.2

77

1.8

90

7.4

166

2.9

143

2.3

65

2.5

80

7.7

176

4.4

145

9.1

0,005

 

 

16

11.5

121

4.9

 

 

 

 

74

5.5

174

4

 

 

 

 

52

14.4

164

2

 

 

0,007

 

 

65

5.7

123

1.2

 

 

 

 

87

0.9

158

10.3

 

 

 

 

74

9.3

131

2.7

 

 

0,01

68

4.4

65

4.6

117

1.2

 

 

66

8.2

80

21.5

172

6

 

 

57

0.3

76

6.2

169

1.5

 

 

0,025

 

 

62

17.1

129

5.7

 

 

 

 

111

15.2

178

5.5

 

 

 

 

92

11.5

181

5.9

 

 

0,05

48

19.4

36

20.5

98

18.4

 

 

67

7.8

58

28

191

10.3

 

 

26

18.9

69

11.6

145

14.2

 

 

0,1

3

1.8

 

 

 

 

22

7.8

1

1

 

 

 

 

158

10.7

0

0

 

 

 

 

118

26.2

0,5

0

0

 

 

 

 

0

0

0

0

 

 

 

 

2

1.7

0

0

 

 

 

 

7

7

1

0

0

 

 

 

 

0

0

0

0

 

 

 

 

69

30

0

0

 

 

 

 

18

18.3

4

 

 

 

 

 

 

3

3.3

 

 

 

 

 

 

7

6

 

 

 

 

 

 

15

10.5

Positive control

443

15

477

10.8

638

64.4

534

18.5

784

43.4

1251

44.5

1214

220.2

1275

25.5

898

13.1

545

17.9

821

57.2

2347

68.6

Abbreviations:

RLI = induced male Sprague Dawley rat liver S9

HLI = induced male Syrian hamster liver S9

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Conclusions:
No mutagenic activity was observed in Salmonella typhimurium strains TA98 or TA100 treated within the closed environment of a desiccator, with or without S9.
Executive summary:

A Salmonella typhimurium mutagenicity test was performed on methyl ethyl ketoxime according to NTP's dessicator procedure (test method similar to OECD Guideline 471). The Salmonella typhimurium strains TA98 and TA100 in either with metabolic activation (S9 mix from Aroclor 1254-induced male Sprague-Dawley rat and Syrian hamster liver) and without metabolic activation were exposed to the test item at concentration of 0 (control), 0.005, 0.007, 0.01, 0.025, 0.05, 0.1, 0.5, 1 mL/chamber. Negative and positive controls were performed satisfactorily. No mutagenic activity was observed in Salmonella typhimurium strains TA98 or TA100 treated within the closed environment of a desiccator, with or without S9.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Test method similar to OECD Guideline 471. No data on GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(no positive control was performed without metabolic activation)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: TA98, TA100, TA1535, TA1537 and TA1538
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (prepared from male Fischer 344 rat liver and Syrian golden hamster liver induced with Aroclor 1254)
Test concentrations with justification for top dose:
Up to 10000 μg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl sulfoxide
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
(TA98, TA358)
Positive control substance:
2-nitrofluorene
Positive controls:
yes
Remarks:
(TA100, TA1535)
Positive control substance:
sodium azide
Positive controls:
yes
Remarks:
(TA1537)
Positive control substance:
9-aminoacridine
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
Evaluation criteria:
To be positive, 2-butanone oxime must cause at least a doubling in the mean revertants per plate of at least one tester strain. The increase in the mean number of revertants per plate must be accompanied by a dose response to increasing concentrations of 2-butanone oxime.
Key result
Species / strain:
other: TA98, TA100, TA1535, TA1537 and TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to 10000 μg/plate)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
2-butanone oxime did not produce a response either with or without exogenous metabolic activation by rat or hamster liver S9 activation enzymes.
Conclusions:
2-butanone oxime did not produce mutagenic response with or without metabolic activation by rat or hamster liver S9 activation enzymes up to 10000 μg/plate.
Executive summary:

A Salmonella typhimurium mutagenicity test was performed on 2 -butanone oxime in accordance with a test method similar to OECD Guideline 471. S. typhimurium TA98, TA100, TA1535, TA1537 and TA1538 strains were exposed to a concentration up to 10000 µg/plate with and without metabolic activation S9 mix prepared from male Fischer 344 rat liver and Syrian golden hamster liver induced with Aroclor 1254. Negative and positive controls were performed satisfactorily. 2 -butanone oxime did not induce a mutagenic response in Salmonella typhimurium tested strains TA98, TA100, TA1535, TA1537 and TA1538 with and without S9 rat or hamster liver enzyme activation.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Test method according to OECD 471 and 472. GLP study.
Qualifier:
according to
Guideline:
other: Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to
Guideline:
OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial gene mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
0 (control), 313, 625, 1250, 2500 and 5000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Untreated negative controls:
yes
Negative solvent / vehicle controls:
not specified
Positive controls:
yes
Remarks:
(TA100, WP2, TA98)
Positive control substance:
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide
Positive controls:
yes
Remarks:
(TA1535)
Positive control substance:
sodium azide
Positive controls:
yes
Remarks:
(TA1537)
Positive control substance:
9-aminoacridine
Positive controls:
yes
Remarks:
(all strains)
Positive control substance:
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

PLATES/TEST: 3
NUMBER OF REPLICATIONS: 2

OTHER: S9: rat liver, induced with phenorbital and 5,6-benzoflavone
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to 5000 µg/plate)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
(up to 5000 µg/plate)
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:

Test item did not induce gene mutation in the S. typhimurium and E. coli strains.

Toxicity was not observed at 5000 µg/plate in five strains either with or without S9 mix.

Conclusions:
Ethyl methyl ketoxime was not mutagenic to Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system under test conditions.
Executive summary:

A bacterial reverse mutation assay was performed on ethyl methyl ketoxime in accordance with OECD Guideline 471. Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA were exposed to a concentration up to 5000 µg/plate with and without metabolic activation S9 mix prepared from rat liver. Negative and positive controls were performed satisfactorily. Ethyl methyl ketoxime was not mutagenic to any of the strains with or without metabolic activation under test conditions. Toxicity was not observed at 5000 µg/plate either with or without S9 mix.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 17 to July 2, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
A standard NTP (National Toxicology Program) protocol.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
not specified
Type of assay:
other: in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (Aroclor 1254-induced male Sprague-Dawley rat liver S9)
Test concentrations with justification for top dose:
Without metabolic activation: 1873, 2497, 3727, 5000 µg/mL
With metabolic activation: 2513, 3750, 5000 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide
Negative solvent / vehicle controls:
yes
Remarks:
(Dimethyl Sulfoxide)
Positive controls:
yes
Positive control substance:
mitomycin C
Positive controls:
yes
Positive control substance:
cyclophosphamide
Details on test system and experimental conditions:
METHOD OF APPLICATION: In the test without S9, cells were incubated in McCoy’s 5A medium with methyl ethyl ketoxime for 18 hours; Colcemid was added and incubation continued for 2 hours. The cells were then harvested by mitotic shake-off, fixed, and stained with Giemsa. For the test with S9, cells were treated with methyl ethyl ketoxime and S9 for 2 hours, after which the treatment medium was removed and the cells incubated for 10 hours in fresh medium, with Colcemid present for the final 2 hours. Cells were harvested in the same manner as for the treatment without S9. The harvest time for the test was based on the cell cycle information obtained in the SCE test; because some cytotoxicity and cell cycle delay were anticipated in the absence of S9, the incubation period was extended. Cells were selected for scoring on the basis of good morphology and completeness of karyotype (21 ± 2 chromosomes). All slides were scored blind and those from a single test were read by the same person. Up to 200 first-division metaphase cells were scored at each dose level. Classes of aberrations included simple (breaks and terminal deletions), complex (rearrangements and translocations), and other (pulverized cells, despiralized chromosomes, and cells containing 10 or more aberrations).
Evaluation criteria:
Chromosomal aberration data are presented as percentages of cells with aberrations. To arrive at a statistical call for a trial, analyses were conducted on both the dose response curve and individual dose points. For a single trial, a statistically significant (P>=0.05) difference for one dose point and a significant trend (P>=0.003) were considered weak evidence for a positive response; significant differences for two or more doses indicated the trial was positive. A positive trend test, in the absence of a statistically significant increase at any one dose resulted in an equivocal call. Ultimately, the trial calls were based on a consideration of the statistical analyses as well as the biological information available to the reviewers.
Statistics:
Significance of percent cells with aberrations tested by the linear regression trend test versus log of the dose. Analyses were conducted on both the dose response curve and individual dose points
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to 5000 µg/mL)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid

Results of Chromosome Aberration test:

Trial #:1   Activation: No Activation   Date: 07/02/1986   Harvest Time: 20.0 hrs   Trial Call: Negative

Dose (µg/mL)

Total Cells Examined

Total Aberrations

Complex Aberrations

Simple Aberrations

Other Abs.

No. of

Abs

% Cells

No. of

Abs

% Cells

No. of

Abs

% Cells

No. of

Abs

% Cells

Abs.

Per

With

Abs.

Per

With

Abs.

Per

With

Abs.

Per

With

Cell

Abs.

Cell

Abs.

Cell

Abs.

Cell

Abs.

Vehicle Control

Negative (Not Specified)

200

2

0.010

1.0

1

0.005

0.5

1

0.005

0.5

0

0.000

0.0

Vehicle Control

Dimethyl Sulfoxide

200

5

0.025

2.5

1

0.005

0.5

4

0.020

2.0

0

0.000

0.0

Test Chemical

 

 

Methyl ethyl ketoxime

 

 

1873

200

2

0.010

1.0

0

0.000

0.0

2

0.010

1.0

0

0.000

0.0

2497

200

5

0.025

2.5

0

0.000

0.0

5

0.025

2.5

0

0.000

0.0

3727

200

1

0.005

0.5

1

0.005

0.5

0

0.000

0.0

0

0.000

0.0

5000

0

0

0.000

0.0

0

0.000

0.0

0

0.000

0.0

0

0.000

0.0

Positive Control

Mitomycin-C

0.05

200

31

0.155

12.5

16

0.080

7.5

15

0.075

6.0

0

0.000

0.0

0.08

25

9

0.360

36.0

4

0.160

16.0

5

0.200

20.0

0

0.000

0.0

Trend

-1.211

0.069

-1.345

 

Probability

0.887

0.472

0.911

 

Trial #:2   Activation: No Activation   Date: 06/17/1986   Harvest Time: 20.0 hrs   Trial Call: Test Failure  

Dose (µg/mL)

Total Cells Examined

Total Aberrations

Complex Aberrations

Simple Aberrations

Other Abs.

No. of

Abs

% Cells

No. of

Abs

% Cells

No. of

Abs

% Cells

No. of

Abs

% Cells

Abs.

Per

With

Abs.

Per

With

Abs.

Per

With

Abs.

Per

With

Cell

Abs.

Cell

Abs.

Cell

Abs.

Cell

Abs.

Vehicle Control

Dimethyl Sulfoxide

 

200

5

0.025

2.0

0

0.000

0.0

5

0.025

2.0

0

0.000

0.0

Test Chemical

Methyl ethyl ketoxime

2500         

200

7

0.035

3.5

0

0.000

0.0

7

0.035

3.5

0

0.000

0.0

Positive Control

Mitomycin-C

 0.08      

25

11

0.440

28.0

4

0.160

12.0

7

0.280

20.0

0

0.000

0.0

Trend

0.000

 

 

0.000

 

0.000

 

 

 

Probability

0.000

0.000

0.000

 

Trial #:1   Activation: Induced Rat Liver S9   Date: 06/17/1986   Harvest Time: 12.0 hrs   Trial Call: Negative  

Dose (µg/mL)

Total Cells Examined

Total Aberrations

Complex Aberrations

Simple Aberrations

Other Abs.

No. of

Abs

% Cells

No. of

Abs

% Cells

No. of

Abs

% Cells

No. of

Abs

% Cells

Abs.

Per

With

Abs.

Per

With

Abs.

Per

With

Abs.

Per

With

Cell

Abs.

Cell

Abs.

Cell

Abs.

Cell

Abs.

Vehicle Control

Negative (Not Specified)

 

200

6

0.030

2.5

2

0.010

1.0

4

0.020

2.0

0

0.000

0.0

Vehicle Control

Dimethyl Sulfoxide

 

200

6

0.030

2.5

2

0.010

1.0

4

0.020

2.0

0

0.000

0.0

Test Chemical

Methyl ethyl ketoxime

2513         

200

6

0.030

2.5

2

0.010

1.0

4

0.020

2.0

0

0.000

0.0

3750         

200

8

0.040

3.0

4

0.020

2.0

4

0.020

1.5

0

0.000

0.0

5000         

200

4

0.020

2.0

1

0.005

0.5

3

0.015

1.5

0

0.000

0.0

Positive Control

Cyclophosphamide

7.5       

200

32

0.160

11.5

13

0.065

4.0

19

0.095

7.5

0

0.000

0.0

37.5       

25

13

0.520

44.0

4

0.160

16.0

9

0.360

32.0

0

0.000

0.0

 

 

Trend

 

-0.166

 

-0.063

 

-0.493

 

Probability

0.566

0.525

0.689

Conclusions:
No increase in chromosomal aberrations was observed in cultured Chinese hamster ovary cells treated with up to 5000 μg/mL methyl ethyl ketoxime, with or without S9
Executive summary:

A cytogenetic Chromosome aberration tests with cultured Chinese hamster ovary cells was performed on methyl ethyl ketoxime according to NTP's standard protocol (test method similar to OECD Guideline 473). Chinese hamster ovary cells were exposed to 2513, 3750, 5000 µg/mL test item with metabolic activation (Aroclor 1254-induced male Sprague-Dawley rat liver S9) and to 1873, 2497, 3727, 5000 µg/mL without metabolic activation for a harvest time of 20 and 12 hours respectively. Up to 200 first-division metaphase cells were scored at each dose level. Classes of aberrations included simple (breaks and terminal deletions), complex (rearrangements and translocations), and other (pulverized cells, despiralized chromosomes, and cells containing 10 or more aberrations). Negative and positive controls were performed satisfactorily. No increase in chromosomal aberrations was observed in cultured Chinese hamster ovary cells treated with up to 5000 μg/mL methyl ethyl ketoxime, with or without S9.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Test method according to an accepted guideline. GLP study.
Qualifier:
according to
Guideline:
other: Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
GLP compliance:
yes
Type of assay:
other: in vitro mammalian chromosome aberration test
Species / strain / cell type:
other: Chinese hamster lung (CHL/IU) cells
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (Rat liver, induced with phenobarbital and 5,6-benzoflavone)
Test concentrations with justification for top dose:
0 (control), 0.22, 0.44, 0.87 mg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
(acetone)
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without S9 mix
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with S9 mix
Details on test system and experimental conditions:
DURATION
- Exposure duration:
With S9 mix: 6, 24 and 48 hours
Without S9 mix: 6 hours

SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays):

PLATES/TEST: 2

NUMBER OF CELLS EVALUATED: 200 cells per groups (chromosome aberrations) and 800 cells per group (polyploid)

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

OTHER EXAMINATIONS:
- Determination of polyploidy: YES
- Others: such as attenuation and premature chromosome condensation.
Statistics:
Cochran Armitage's trend test was dose at p<0.05 when the incidence of TAG or polyploid in the treatment groups was significantly different from historical solvent control at p<0.05 by Fisher's exact test.
Key result
Species / strain:
other: Chinese hamster lung (CHL/IU) cells
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to 0.87 mg/mL)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
(up to 0.87 mg/mL)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

Test item did not induce structural chromosomal aberrations with and without an exogenous metabolic activation system under the conditions of this experiment

Conclusions:
Ethyl methyl ketoxime induced neither structural chromosomal aberrations nor polyploidy in Chinese hamster lung (CHL/IU) cells up to the limit concentration of 10 mM (0.87 mg/ml), in the absence or presence of an exogenous metabolic activation system under test conditions.
Executive summary:

An in vitro mammalian cell chromosome aberration assay was performed on ethyl methyl ketoxime in accordance with Guidelines for Screening Mutagenicity Testing of Chemicals (Japan). Chinese hamster lung (CHL/IU) cells were exposed to a concentration up to 0.87 mg/mL for 6 hours with metabolic activation and for 6, 24 and 48 hours without metabolic activation (S9 mix prepared from rat liver). Negative and positive controls were performed satisfactorily. Ethyl methyl ketoxime induced neither structural chromosomal aberrations nor polyploidy in Chinese hamster lung (CHL/IU) cells up to the limit concentration of 10 mM (0.87 mg/ml), in the absence or presence of an exogenous metabolic activation system under test conditions.

Endpoint:
in vitro DNA damage and/or repair study
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
May 28, 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
A standard NTP (National Toxicology Program) protocol.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
GLP compliance:
not specified
Type of assay:
sister chromatid exchange assay in mammalian cells
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (Aroclor 1254-induced male Sprague-Dawley rat liver S9)
Test concentrations with justification for top dose:
Without metabolic activation: 16.7, 50, 166.7, 500 µg/mL
With metabolic activation: 500, 1666.7, 5000 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide
Negative solvent / vehicle controls:
yes
Remarks:
(Dimethyl Sulfoxide)
Positive controls:
yes
Positive control substance:
mitomycin C
Positive controls:
yes
Positive control substance:
cyclophosphamide
Details on test system and experimental conditions:
METHOD OF APPLICATION: In the SCE test without S9, CHO cells were incubated for 25.5 hours with methyl ethyl ketoxime in supplemented McCoy’s 5A medium. Bromodeoxyuridine (BrdU) was added 2 hours after culture initiation. After 25.5 hours, the medium containing methyl ethyl ketoxime was removed and replaced with fresh medium plus BrdU and Colcemid, and incubation was continued for 2 hours. Cells were then harvested by mitotic shake-off, fixed, and stained with Hoechst 33258 and Giemsa. In the SCE test with S9, cells were incubated with methyl ethyl ketoxime, serum-free medium, and S9 for 2 hours. The medium was then removed and replaced with medium containing serum and BrdU and no methyl ethyl ketoxime. Incubation proceeded for an additional 25.5 hours, with Colcemid present for the final 2 hours. Harvesting and staining were the same as for cells treated without S9. All slides were scored blind and those from a single test were read by the same person. Up to 50 second-division metaphase cells were scored for frequency of SCEs per cell from each dose level.
Evaluation criteria:
An SCE frequency 20% above the concurrent solvent control value was chosen as a statistically conservative positive response. The probability of this level of difference occurring by chance at one dose point is less than 0.01; the probability for such a chance occurrence at two dose points is less than 0.001. An increase of 20% or greater at any single dose was considered weak evidence of activity; increases at two or more doses indicated that the trial was positive. A statistically significant trend (P<0.005) in the absence of any responses reaching 20% above background led to a call of equivocal.
Statistics:
Significance of SCEs/chromosome tested by the linear regression trend test versus log of the dose.
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to 500 µg/mL without S9; up to 5000 µg/mL with S9)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Cytostatic at 500 µg/mL with this concentration

Results of Sister Chromatid Exchange test:

Trial #:1   Activation: No Activation   Date: 05/28/1986   Trial Call: Negative  

Dose

(µg/mL)

Number
Cells
Examined

Number Chromosomes Examined

Total Number SCEs

SCE / Chromosome

SCE / Cell

Hours in BRDU

% Increase Over Solvent Control

Vehicle Control

Dimethyl Sulfoxide

 

50

1029

386

0.375

7.72

25.5

0.000

Test Chemical

Methyl ethyl ketoxime

16.7       

50

1025

376

0.367

7.52

25.5

-2.211

50         

50

1045

423

0.405

8.46

25.5

7.908

166.7       

50

1020

438

0.429

8.76

25.5

14.473

500         

0

0

0

0.000

0.00

0.0

N/A

Positive Control

Mitomycin-C

 0.001     

50

1035

540

0.522

10.80

25.5

39.085

 0.01      

5

104

174

1.673

34.80

25.5

346.009

 

 

Trend

2.291

 

Probability

0.011

 

Trial #:1   Activation: Induced Rat Liver S9   Date: 05/28/1986   Trial Call: Negative  

Dose µg/mL

Number
Cells
Examined

Number Chromosomes Examined

Total Number SCEs

SCE / Chromosome

SCE / Cell

Hours in BRDU

% Increase Over Solvent Control

Vehicle Control

Dimethyl Sulfoxide

 

50

1039

428

0.412

8.56

25.5

0.000

Test Chemical

Methyl ethyl ketoxime

500         

50

1018

357

0.351

7.14

25.5

-14.868

1666.7       

50

1016

395

0.389

7.90

25.5

-5.621

5000         

50

1026

415

0.404

8.30

25.5

-1.809

Positive Control

Cyclophosphamide

 0.4       

50

1025

602

0.587

12.04

25.5

42.575

2         

5

103

154

1.495

30.80

25.5

262.957

 

Trend

 

0.166

 

Probability

 

0.434

 

Conclusions:
No induction of sister chromatid exchanges was observed at concentrations up to toxicity (500 μg/mL) in the absence of S9 or up to the assay limit (5000 μg/mL) in the presence of S9.
Executive summary:

A Sister Chromatid Exchange tests with cultured Chinese hamster ovary cells was performed on methyl ethyl ketoxime according to NTP's standard protocol (test method similar to OECD Guideline 479). Chinese hamster ovary cells were exposed to 500, 1666.7, 5000 µg/mL test item with metabolic activation (Aroclor 1254-induced male Sprague-Dawley rat liver S9) and to 16.7, 50, 166.7, 500 µg/mL without metabolic activation for a harvest time of 25.5 hours both. Negative and positive controls were performed satisfactorily. p to 50 second-division metaphase cells were scored for frequency of SCEs per cell from each dose level. No induction of sister chromatid exchanges was observed at concentrations up to toxicity (500 μg/mL) in the absence of S9 or up to the assay limit (5000 μg/mL) in the presence of S9.

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:
comparable to guideline study with acceptable restrictions
Remarks:
Test method similar to OECD Guideline 476. No data on GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
not specified
Type of assay:
other: mammalian cell gene mutation assay
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (prepared from Aroclor 1254-induced male Fisher 344 rats)
Test concentrations with justification for top dose:
Without metabolic activation: 0 (control), 2.8, 3.6, 4.6, 5.5 and 6.5 µl/mL
With metabolic activation: 0 (control), 1.7, 2.8, 3.6, 4.6, 5.5 and 6.5 µl/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl sulfoxide
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Positive controls:
yes
Positive control substance:
other: 3-methylcholanthrene
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
(only with cytotoxicity in the absence of S9)
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
2-butanone oxime showed evidence of mutagenic activity in the absence of S9 activation, but in the presence of cytotoxicity (it was noted that there was a dose response for both mutant frequency and relative total colony growth). No evidence of mutagenic activity was observed in the presence of S9 activation.

Results obtainend without metabolic activation:

Dose (µg/mL)

Relative total growth

(% of control)

Mutant frequency

(100,000 survivors)

0

100

0.50

2.8

50.0

0.75

3.6

35.5

0.95

4.6

28.5

1.3

5.5

12.5

2.0

6.5

7.5

2.65

There was a dose response for both mutant frequency and relative total colony growth.

Conclusions:
2-butanone oxime was negative for mutagenic activity in mouse lymphoma L5178Y cells in the presence of S9 metabolic activation, but was positive in the absence of S9 metabolic activation and in the presence of cytotoxicity.
Executive summary:

A mammalian cell mutagenicity test was performed on 2 -butanone oxime in accordance with a test method similar to OECD Guideline 476. Mouse lymphoma L5178Y cells were exposed to concentrations up to 6.5 µg/plate with and without metabolic activation S9 mix prepared from Aroclor 1254-induced male Fisher 344 rats. Negative and positive controls were performed satisfactorily. 2-butanone oxime was negative for mutagenic activity in mouse lymphoma L5178Y cells in the presence of S9 metabolic activation, but was positive in the absence of S9 metabolic activation and in the presence of cytotoxicity.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
other: TA97, TA98, TA100, TA1535
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
(at strain 1535 with induced male Syrian hamster liver S9)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Read-across from an analogue substance
Conclusions:
Based on the read-across approach from experimantal results on analogue butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic in strains TA97, TA98, or TA100 with and without S9 and mutagenic in strain TA1535, with S9 syrian hamster liver metabolic activation but non-mutagenic with S9 rat liver metabolic activation nor without metabolic activation.
Executive summary:

A Salmonella typhimurium mutagenicity test was performed on analogue substance butanone oxime up to 10000 µg/plane according to NTP's preincubation protocol (test method similar to OECD Guideline 471). Based on the results on butanone oxime, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic in strains TA97, TA98, or TA100 with and without S9 up to an estimate concentration of 11994.18 µg/plate. The analogue butanone oxime was observed to be mutagenic over a concentration range of 100 to 10000 μg/plate, only in Salmonella typhimurium strain TA1535 and in the presence of induced hamster liver S9 but not in the presence of induced rat liver S9 nor without exogenous metabolic activation. Based on the read-across approach from these results, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be at most weakly genotoxic since it induced mutations under very specific conditions (strain 1535 with S9 syrian hamster liver).

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
other: TA98, TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 1.20 mL/chamber)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on the read-across approach from analogue butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic with or without metabolic activation under test condition.
Executive summary:

A Salmonella typhimurium mutagenicity test was performed on butanone oxime up to 1 mL/chamber according to NTP's dessicator procedure (test method similar to OECD Guideline 471). No mutagenic activity was observed in Salmonella typhimurium strainsTA98 or TA100 treated within the closed environment of a desiccator, with or without metabolic activation. Based on these result, the read-across was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic up to 1.20 mL/chamber under test conditions.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
other: TA98, TA100, TA1535, TA1537 and TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 11994.18 µg/plate)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on the read-across approach from analogue butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic with or without metabolic activation under test condition.
Executive summary:

A Salmonella typhimurium mutagenicity test was performed on analogue substance butanone oxime up to 10000 µg/plate in accordance with a test method similar to OECD Guideline 471. Butanone oxime did not induce a mutagenic response in Salmonella typhimurium tested strains TA98, TA100, TA1535, TA1537 and TA1538 with and without S9 rat or hamster liver enzyme activation. Based on the read-across approach from these experimental results, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic up to an estimated concentration of 11994.18 µg/plate with and with metabolic activation and under test conditions.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 5997.09 µg/plate)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
(up to an estimated concentration of 5997.09 µg/plate)
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Read across form an analogue substance
Conclusions:
Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic with or without metabolic activation under test conditions.
Executive summary:

A bacterial reverse mutation assay was performed on the analogue substance butanone oxime up to 5000 µg/plate in accordance with OECD Guideline 471. Butanone oxime was not mutagenic to any of the strains (Salmonella typhimurium TA100, TA1535, TA98, TA1537 andEscherichia coli WP2 uvrA) with or without metabolic activation. Based on these results, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic up to an estimated concentration of 5997.09 µg/plate with and with metabolic activation and under test conditions.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 5997.09 µg/mL)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-clastogenic with or without metabolic activation under test conditions.
Executive summary:

A cytogenetic Chromosome aberration tests with cultured Chinese hamster ovary cells was performed on analogue substance butanone oxime up to 5000 µg/ml according to NTP's standard protocol (test method similar to OECD Guideline 473).No increase in chromosomal aberrations was observed on the analogue substance with or without metabolic activation for a harvest time of 20 and 12 hours respectively. Based on the read-across approach, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-clastogenic up to and estimated concentration of 5997.09 µg/mL with and without metabolic activation and under test conditions.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
other: Chinese hamster lung (CHL/IU) cells
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 1.04 mg/mL)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
(up to an estimated concentration of 1.04 mg/mL)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-clastogenic with or without metabolic activation under test conditions.
Executive summary:

An in vitro mammalian cell chromosome aberration assay was performed on the analogue substance butanone oxime up to 0.87 mg/mL in accordance with Guidelines for Screening Mutagenicity Testing of Chemicals (Japan). The analogue butanone oxime induced neither structural chromosomal aberrations nor polyploidy in Chinese hamster lung (CHL/IU) cells up to the limit concentration of 10 mM (0.87 mg/ml), in the absence or presence of an exogenous metabolic activation system under test conditions. Base on the read-across approach from these results, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-clastogenic up to an estimated concentration of 1.04 mg/mL with or without metabolic activation and under test conditions.

Endpoint:
in vitro DNA damage and/or repair study
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 599.71 μg/mL without S9 and 5997.09 μg/mL with S9)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined not to induce sister chromatid exchanges with or without metabolic activation under test conditions.
Executive summary:

A Sister Chromatid Exchange tests with cultured Chinese hamster ovary cells was performed on the analogue substance butanone oxime up to 500 µg/mL with metabolic activation and up to 5000 µg/mL without metabolic activation according to NTP's standard protocol (test method similar to OECD Guideline 479). No induction of sister chromatid exchanges was observed at concentrations up to toxicity (500 μg/mL) in the absence of S9 or up to the assay limit (5000 μg/mL) in the presence of S9. Based on these results, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined not to induce sister chromatid exchanges up to an estimated concentration of 599.71 µg/mL with metabolic activation and 5997.09 µg/mL without metabolic activation, under test conditions.

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:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
(only with cytotoxicity in the absence of S9)
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
Based on experimental data on analogue butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be mutagenic in the absence of S9 activation, but only in the presence of cytotoxicity. Test item is determined to be non-mutagenic in the presence of S9 activation.
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be negative for mutagenic activity in mouse lymphoma L5178Y cells in the presence of S9 metabolic activation, but positive in the absence of S9 metabolic activation and in the presence of cytotoxicity.
Executive summary:

A Mouse Lymphoma L5178Y mammalian cell mutagenicity test was performed on the analogue test substance butanone oxime up to 6.5 µg/plate in accordance with a test method similar to OECD Guideline 476. The analogue butanone oxime was negative for mutagenic activity in the presence of S9 metabolic activation, but positive in the absence of S9 metabolic activation and in the presence of cytotoxicity. Based on the read-across approach from these results, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic with metabolic activation and mutagenic without metabolic activation but in presence of cytotoxicity up to an estimated concentration of 7.80 µg/plate under test conditions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Key study: Based on read-across approach from experimental data on analogue butanone oxime (test method similar to OECD 474), butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be negative for in vivo cytogenicity in mammalian cells.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 19, 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
A standard NTP (National Toxicology Program) protocol.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
(no positive control was performed)
GLP compliance:
not specified
Type of assay:
other: micronucleus assay
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
- Vehicle(s)/solvent(s) used: water
Duration of treatment / exposure:
13 weeks.
Frequency of treatment:
Daily.
Dose / conc.:
0 ppm
Remarks:
nominal
Dose / conc.:
625 ppm
Remarks:
nominal
Dose / conc.:
1 250 ppm
Remarks:
nominal
Dose / conc.:
2 500 ppm
Remarks:
nominal
Dose / conc.:
5 000 ppm
Remarks:
nominal
Dose / conc.:
10 000 ppm
Remarks:
nominal
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Remarks:
males and females
Dose / conc.:
110 mg/kg bw/day (actual dose received)
Remarks:
males
Dose / conc.:
200 mg/kg bw/day (actual dose received)
Remarks:
males
Dose / conc.:
515 mg/kg bw/day (actual dose received)
Remarks:
males
Dose / conc.:
755 mg/kg bw/day (actual dose received)
Remarks:
males
Dose / conc.:
1 330 mg/kg bw/day (actual dose received)
Remarks:
males
Dose / conc.:
145 mg/kg bw/day (actual dose received)
Remarks:
females
Dose / conc.:
340 mg/kg bw/day (actual dose received)
Remarks:
females
Dose / conc.:
630 mg/kg bw/day (actual dose received)
Remarks:
females
Dose / conc.:
1 010 mg/kg bw/day (actual dose received)
Remarks:
females
Dose / conc.:
3 170 mg/kg bw/day (actual dose received)
Remarks:
females
No. of animals per sex per dose:
5 animals per sex per dose.
Control animals:
yes, concurrent vehicle
Positive control(s):
none;
Tissues and cell types examined:
Mouse peripheral blood erythrocytes
Details of tissue and slide preparation:
At the end of the 13-week drinking water study, blood samples were obtained from male and female mice. Smears were immediately prepared and fixed in absolute methanol. The methanol-fixed slides were stained with a chromatin-specific fluorescent dye (acridine orange) and coded. Slides were scanned to determine the frequency of micronuclei in 2,000 normochromatic eythrocytes (NCEs) in each of 5 animals per exposure group
Evaluation criteria:
An individual trial is considered positive if the trend test P value is less than or equal to 0.025 or if the P value for any single exposure group is less than or equal to 0.025 divided by the number of exposure groups. A final call of positive for micronucleus induction is preferably based on reproducibly positive trials. Results of the 13-week studies were accepted without repeat tests, because additional test data could not be obtained. Ultimately, the final call is determined by the scientific staff after considering the results of statistical analyses, the reproducibility of any effects observed, and the magnitudes of those effects.
Statistics:
The frequency of micronucleated cells among NCEs was analyzed by a statistical software package that tested for increasing trend over exposure groups with a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each exposure group and the control group In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation
Key result
Sex:
male/female
Genotoxicity:
negative
Remarks:
(up to 10000 ppm)
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined

Frequency of Micronuclei in Peripheral Blood Erythrocytes of Mice Following Treatment with Methyl Ethyl Ketoxime in Drinking Water for 13 Weeks:

A79779 -1

Start Date

Sample Collection Time

Sex

Cell

Methodology Used

Dosing Regimen

Route

Trend Test P-Value

02/19/1991

0 Hours

Female

NCE

Slide Scoring

WATER x 93, 93 Days

Dosed-Water

0.998

Dose (ppm)

Number of Animals Scored

Mean MN-NCE/1000 NCE ± SEM

Pairwise P

Vehicle Control

Water

 0         

5

2.00 ± 0.35

 

Test Chemical

Methyl ethyl ketoxime

625         

5

2.10 ± 0.58

0.4379

1250         

5

3.00 ± 0.42

0.0784

2500         

5

2.90 ± 0.89

0.0990

5000         

5

1.90 ± 0.37

0.5637

10000         

5

0.80 ± 0.34

0.9884

A79779 -2

Start Date

Sample Collection Time

Sex

Cell

Methodology Used

Dosing Regimen

Route

Trend Test P-Value

02/19/1991

0 Hours

Male

NCE

Slide Scoring

WATER x 92, 92 Days

Dosed-Water

1.000

Dose (ppm)

Number of Animals Scored

Mean MN-NCE/1000 NCE ± SEM

Pairwise P

Vehicle Control

Water

0

5

4.80 ± 0.68

Test Chemical

Methyl ethyl ketoxime

625

5

4.50 ± 0.76

0.6224

1250

5

4.00 ± 0.16

0.8036

2500

5

3.70 ± 0.34

0.8841

5000

5

1.40 ± 0.37

10.000

10000

5

1.60 ± 0.19

10.000

NCE=normochromatic erythrocyte

Conclusions:
No increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of male or female mice administered methyl ethyl ketoxime via drinking water at concentrations from 625 to 10000 ppm for 13 weeks.
Executive summary:

A Mammalian Erythrocyte Micronucleus Test was performed on methyl ethyl ketoxima according to NTP's standard protocol (test method similar to OECD Guideline 474). 5 mice per sex and per dose were exposed to test item at 0 (control, water), 625, 1250, 2500, 5000 and 10000 ppm (0, 110, 200, 515, 755, 1330 mg/kg bw/day males and 0, 145, 340, 630, 1010, 3170 mg/kg bw/day females) for 13 weeks by drinking water. At the end of the exposure, blood samples were obtained from male and female mice, smears were prepared, fixed in absolute methanol and stained with a chromatin-specific fluorescent dye (acridine orange). Slides were scanned to determine the frequency of micronuclei in 2000 normochromatic eythrocytes (NCEs) in each of 5 animals per exposure group. No increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of male or female mice administered methyl ethyl ketoxime via drinking water at concentrations from 625 to 10000 ppm (1130 mg/kg bw/day males and 3170 mg/kg bw/day females) for 13 weeks. The percentage of normochromatic erythrocytes among the population of circulating erythrocytes was markedly decreased at the highest dose tested in male and female mice.

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Butan-2-one O,O',O''-(vinylsilanetriyl)oxime undergoes rapid hydrolysis in aqueous to butanone oxime and the corresponding silanol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to butanone oxime and their values are comparable.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Sex:
male/female
Genotoxicity:
negative
Remarks:
(up to an estimated concentration of 1199.18 ppm)
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined
Remarks on result:
other: Read across from an analogue substance
Conclusions:
Based on read-across approach from experimental data on the analogue butanone oxime, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined not to cause cytogenetic damage based on the in-vivo micronucleous test up to an estimated concentration of 11994.18 ppm (1595.23 mg/kg bw/day in males and 3802.16 mg/kg bw/day in females) and under test conditions.
Executive summary:

A Mammalian Erythrocyte Micronucleus Test was performed on the analogue substance butanone oxime up to 10000 ppm (1330 mg/kg bw/day in males and 3170 mg/kg bw in females) according to NTP's standard protocol (test method similar to OECD Guideline 474). No increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of male or female mice administered butanone oxime via drinking water for 13 weeks under test conditions. The percentage of normochromatic erythrocytes among the population of circulating erythrocytes was markedly decreased at the highest dose tested in male and female mice. Based on these results, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined not to cause cytogenetic damage based on the in-vivo micronucleous test up to an estimated concentration of 11994.18 ppm (1595.23 mg/kg bw/day in males and 3802.16 mg/kg bw/day in females) and under test conditions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

In vitro gene mutation in bacteria: Read-across from experimental data on the analogue substance butanone oxime: Weight of evidence:

A Salmonella typhimurium mutagenicity test was performed on analogue substance butanone oxime up to 10000 µg/plane according to NTP's preincubation protocol (test method similar to OECD Guideline 471). Based on the obteined experimental results, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic in strains TA97, TA98, or TA100 with and without S9 up to an estimate concentration of 1199.18 µg/plate and mutagenic only in the strain TA1535 and in the presence of induced hamster liver S9 but not in the presence of induced rat liver S9 nor without exogenous metabolic activation.

Moreover, as part of study this study, a NTP's dessicator procedure was performed on the analgoue butanone oxime up to 1 mL/chamber on Salmonella typhimurim strains TA98 and TA100. Based on the read-across approach, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic up to and estimated concentration of 1.20 mL/chamber under test conditions.

Based on the read-across approach from the experimental results obtained in the study conducted by Rogers-Back et al. on the analogue butanone oxime, where the analogue butanone oxime did not induce a mutagenic response in Salmonella typhimurium tested strains TA98, TA100, TA1535, TA1537 and TA1538 with and without S9 rat or hamster liver enzyme activation, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic up to an estimated concentration of 1199.18 µg/plate with and with metabolic activation and under test conditions.

In the study performed by the Ministry of Health, Labour and Welfare of Japan, a bacterial reverse mutation assay was performed on the analogue substance butanone oxime in accordance with OECD Guideline 471. The analogue butanone oxime was not mutagenic to any of the strains (Salmonella typhimurium TA100, TA1535, TA98, TA1537 andEscherichia coli WP2 uvrA) with or without metabolic activation. Based on these resulta, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic up to an estimated concentration of 5997.09 µg/plate with and with metabolic activation and under test conditions.

According to the available data, the weight of evidence approach was applied and the test item butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be negative for in vitro gene mutation in bacteria.

In vitro cytogenicity in mammalian cells (chromosome aberration): Read-across from experimental data on analogue butanone oxime:

Key study: A cytogenetic Chromosome aberration tests with cultured Chinese hamster ovary cells was performed on analogue substance butanone oxime up to 5000 µg/ml according to NTP's standard protocol (test method similar to OECD Guideline 473). No increase in chromosomal aberrations was observed on the analogue substance with or without metabolic activation for a harvest time of 20 and 12 hours respectively. Based on the read-across approach, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-clastogenic up to and estimated concentration of 5997.09 µg/mL with and without metabolic activation and under test conditions.

Key study: In a study performed by the Ministry of Health, Labour and Welfare from Japan, an in vitro mammalian cell chromosome aberration assay was performed on the analogue substance butanone oxime up to 0.87 mg/mL in accordance with Guidelines for Screening Mutagenicity Testing of Chemicals (Japan). The analogue butanone oxime induced neither structural chromosomal aberrations nor polyploidy in Chinese hamster lung (CHL/IU) cells up to the limit concentration of 10 mM (0.87 mg/ml), in the absence or presence of an exogenous metabolic activation system under test conditions. Base on the read-across approach from these results, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-clastogenic up to an estimated concentration of 1.04 mg/mL with or without metabolic activation and under test conditions.

The test item butan-2 -one O,O',O''-(vinylsilanetriyl)oxime was determined to be negative for in vitro cytogenicity in mammalian cells.

In vitro gene mutation in mammalian cells: Read-across from experimental data on analogue butanone oxime:

Key study: In the study by Rogers-Back et al., a Mouse Lymphoma L5178Y mammalian cell mutagenicity test was performed on the analogue test substance butanone oxime up to 6.5 µg/plate in accordance with a test method similar to OECD Guideline 476. The analogue butanone oxime was negative for mutagenic activity in the presence of S9 metabolic activation, but positive in the absence of S9 metabolic activation and in the presence of cytotoxicity. Based on the read-across approach from these results, butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be non-mutagenic with metabolic activation and mutagenic without metabolic activation but in presence of cytotoxicity up to an estimated concentration of 7.80 µg/plate under test conditions.

Since mutagenicity was observed only in presence of cytotoxicity and in absence of metabolic activation, it cannot be concluded that butan-2 -one O,O',O''-(vinylsilanetriyl)oxime induced gene mutation in mammalian cells.

In vivo cytogenicity in mammalian cells: Read-across approach from experimental results on the analogue substance butanone oxime:

Key study: A Mammalian Erythrocyte Micronucleus Test was performed on the analogue substance butanone oxime up to 10000 ppm (1330 mg/kg bw/day in males and 3170 mg/kg bw in females) according to NTP's standard protocol (test method similar to OECD Guideline 474). No increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of male or female mice administered butanone oxime via drinking water for 13 weeks under test conditions. The percentage of normochromatic erythrocytes among the population of circulating erythrocytes was markedly decreased at the highest dose tested in male and female mice. Based on these results, the read-across approach was applied and butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined not to cause cytogenetic damage based on the in-vivo micronucleous test up to an estimated concentration of 11994.18 ppm (1595.23 mg/kg bw/day in males and 3802.16 mg/kg bw/day in females) and under test conditions.

Butan-2 -one O,O',O''-(methylsilanetriyl)oxime was determined to be negative for in vivo cytogenicity in mammalian cells.

Justification for classification or non-classification

Based on the available information on genetic toxicity in vitro and in vivo, butan-2 -one O,O',O''-(vinylsilanetriyl)oxime was considered to be negative for genetic toxicity, and therefore the substance is not classified according to CLP Regulation (EC) 1272/2008.