Butan-2-one O,O',O'',O'''-silanetetrayltetraoxime

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'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime induces gene mutation in mammalian cells.

Link to relevant study records

Reference

Reference 1

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached 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'',O'''-silanetetrayltetraoxime 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.

Conclusions:

Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime 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 6.95 µg/plate under test conditions.

Reference 2

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached 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 534.52 μg/mL without S9 and 5345.21 μg/mL with S9)

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined not to induce sister chromatid exchanges up to an estimated concentration of 534.52 µg/mL with metabolic activation and 5345.21 µg/mL without metabolic activation, under test conditions.

Reference 3

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached 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 0.93 mg/mL)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(up to an estimated concentration of 0.93 mg/mL)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-clastogenic up to an estimated concentration of 0.93 mg/mL with or without metabolic activation and under test conditions.

Reference 4

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached 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 5345.21 µg/mL)

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-clastogenic up to and estimated concentration of 5345.21 µg/mL with and without metabolic activation and under test conditions.

Reference 5

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(up to an estimated concentration of 5345.21 µg/plate)

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the read-across approach from experimental data on butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic up to an estimated concentration of 5345.21 µg/plate with and with metabolic activation and under test conditions.

Reference 6

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 10690.43 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 10690.43 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 10690.43 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 10690.43 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 10690.43 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Conclusions:

Based on the read-across approach from analogue butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic up to an estimated concentration of 10690.43 µg/plate with and with metabolic activation and under test conditions.

Reference 7

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached 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 1.07 mL/chamber)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Based on published experimental data on the analogue substance butanone oxime which is considered to be non-mutagenic on S. typhimurium TA97, TA98, TA100 and TA1535, with and without metabolic activation, and applying the read-across approach, the substance butan-2-one O,O',O'',O'''-silanetetrayltetraoxime was also considered as non-mutagenic under test conditions.

Conclusions:

Based on the read-across approach from analogue butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic up to 1.07 mL/chamber under test conditions.

Reference 8

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached 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

Conclusions:

Based on the read-across approach from experimantal results on analogue butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic in strains TA97, TA98, or TA100 with and without S9 up to an estimate concentration of 10690.43 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'',O'''-silanetetrayltetraoxime was determined to be at most weakly genotoxic since it induced mutations under very specific conditions (strain 1535 with S9 syrian hamster liver).

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'',O'''-silanetetrayltetraoxime was determined to be negative for in vivo cytogenicity in mammalian cells.

Link to relevant study records

Reference

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
The target substance TOS is an oxime silane that undergoes rapid hydrolysis in aqueous to MEKO and the corresponding silanol. At the same time, silanols undergo continuous condensation reaction to produce higher molecular weight siloxanes which are in the molecular weight range large enough to be considered biologically unavailable. Therefore, the toxicity of TOS is due to the hydrolysis product MEKO and their values are comparable.
See attached reporting format.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Genotoxicity:

negative

Remarks:

(up to an estimated concentration of 10690.43 ppm)

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not examined

Conclusions:

Based on read-across approach from experimental data on the analogue butanone oxime, butan-2-one O,O',O'',O'''-silanetetrayltetraoxime was determined not to cause cytogenetic damage based on the in-vivo micronucleous test up to an estimated concentration of 10690.43 ppm (1421.83 mg/kg bw/day in males and 3388.87 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'',O'''-silanetetrayltetraoxime was determined not to cause cytogenetic damage based on the in-vivo micronucleous test up to an estimated concentration of 10690.43 ppm (1421.83 mg/kg bw/day in males and 3388.87 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic in strains TA97, TA98, or TA100 with and without S9 up to an estimate concentration of 10690.43 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic up to and estimated concentration of 1.07 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic up to an estimated concentration of 10690.43 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'',O'''-silanetetrayltetraoxime was determined to be non-mutagenic up to an estimated concentration of 5345.21 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'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined to be non-clastogenic up to and estimated concentration of 5345.21 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'',O'''-silanetetrayltetraoxime was determined to be non-clastogenic up to an estimated concentration of 0.93 mg/mL with or without metabolic activation and under test conditions.

 

The test item butan-2-one O,O',O'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime 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 6.95 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'',O'''-silanetetrayltetraoxime 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'',O'''-silanetetrayltetraoxime was determined not to cause cytogenetic damage based on the in-vivo micronucleous test up to an estimated concentration of 10690.43 ppm (1421.83 mg/kg bw/day in males and 3388.87 mg/kg bw/day in females) and under test conditions.

 

Butan-2-one O,O',O'',O'''-silanetetrayltetraoxime was determined to be negative for in vivo cytogenicity in mammalian cells.

 

Justification for selection of genetic toxicity endpoint

No study was selected, since the studies were negative in a weight of evidence approach.

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'',O'''-silanetetrayltetraoxime was considered to be negative for genetic toxicity, and therefore the substance is not classified according to CLP Regulation (EC) No 1272/2008.