Butan-2-one O,O',O''-(vinylsilylidyne)trioxime

Endpoint summary

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: Weight of evidence: 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

Reference

Reference 1

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

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:

S. typhimurium, 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:

S. typhimurium, 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.

Reference 2

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 for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

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:

S. typhimurium, 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:

S. typhimurium, 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.

Reference 3

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

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:

S. typhimurium, 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:

S. typhimurium, 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.

Reference 4

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

Guideline:

other: Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

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.

Reference 5

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

weight of evidence

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

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.

Reference 6

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

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 an accepted guideline. GLP study.

Qualifier:

according to guideline

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.

Reference 7

Endpoint:

in vitro DNA damage and/or repair study

Type of information:

experimental study

Adequacy of study:

weight of evidence

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

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.

Reference 8

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

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.

Reference 9

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 for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium, 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).

Reference 10

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 for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium, 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.

Reference 11

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 for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium, 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.

Reference 12

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 for cross-reference:

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.

Reference 13

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 for cross-reference:

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.

Reference 14

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 for cross-reference:

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.

Reference 15

Endpoint:

in vitro DNA damage and/or repair study

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 for cross-reference:

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.

Reference 16

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 for cross-reference:

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

Reference

Reference 1

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

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.

Reference 2

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 for cross-reference:

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: Weight of evidence:

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.

 

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.