Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro bacteria reverse mutation and in vitro mammalian chromosome aberration: Weight of evidence: Experimental results from studies performed with the supporting substances acetic acid and sodium acetate. All study results were negative. Based on these results, the read-across approaches were applied and triacetoxyvinylsilane is considered negative under test conditions.

In vitro gene mutation in mammalian cells: Key study: Based on experimental results with analogue substance propyltriacetoxysilane, the read-across approach was applied and triacetoxyvinylsilane is considered to be non-mutagenic under test conditions.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Test within the National Toxicology Program’s mutagenicity testing program and according to GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(Only 4 strains were tested)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1535 and TA 97
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix (fractions of Aroclor 1254-induced, male Sprague-Dawley rat and male Syrian hamster livers)
Test concentrations with justification for top dose:
100, 333, 1000, 3333, 6666, and 10000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Distilled water
Negative solvent / vehicle controls:
yes
Remarks:
(Distilled water)
Positive controls:
yes
Remarks:
(Without metabolic activation)
Positive control substance:
sodium azide
Remarks:
(For strains TA 1535 and TA 100)
Positive controls:
yes
Remarks:
(Without metabolic activation)
Positive control substance:
9-aminoacridine
Remarks:
(For strain TA 97)
Positive controls:
yes
Remarks:
(Without metabolic activation)
Positive control substance:
other: 4-nitro-o-phenylenediamine
Remarks:
(For strain TA 98)
Positive controls:
yes
Remarks:
(With metabolic activation)
Positive control substance:
other: 2-aminoanthracene
Remarks:
(For all strains)
Details on test system and experimental conditions:
The test chemical (0.05 mL), overnight culture of Salmonella (0.05 mL), and S-9 mix or buffer (0.5 mL), were incubated at 37 ºC, without shaking, for 20 min.
The top agar was added and the contents of the tubes were mixed and poured onto the surface of petri dishes containing Vogel-Bonner medium.

Histidine-independent colonies arising on these plates were counted following two days incubation at 37 ºC.

Number of replications: 3 plates/dose
Evaluation criteria:
Test substance was judged mutagenic or weakly mutagenic if it produced a reproducible, dose-related response over the solvent control, under a single metabolic activation condition, in replicate trials.
Test substance was judged questionable if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a weakly mutagenic response, or if only single doses produced increases in his+ revertants in repeat trials.
Test substance was judge nonmutagenic if it did not meet the criteria for a mutagenic or questionable response.
Key result
Species / strain:
S. typhimurium, other: TA 98, TA 100, TA 1535, and TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(at 10000 µg/plate)
Vehicle controls validity:
valid
Positive controls validity:
valid

Acetic acid did not show any mutagenic effect under test conditions, with and without metabolic activation.

Conclusions:
Acetic acid did not show any mutagenic effect under test conditions, with and without metabolic activation.
Executive summary:

A standard Ames test was carried out with Acetic acid using Salmonella typhimurium strains TA 98, TA 100, TA 1535, and TA 97. The test was performed with and without metabolic activation. The concentrations of Acetic acid were 100, 333, 1000, 3333, 6666, and 10000 µg/plate.

Acetic acid did not show any mutagenic effect under test conditions.

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 was similar to OECD 471. No GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
9000 x g supernatant of liver from rats predosed with Aroclor 1254.
Test concentrations with justification for top dose:
No data
Vehicle / solvent:
No data
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
(Without metabolic activation)
Positive control substance:
other: streptozotocin
Positive controls:
yes
Remarks:
(With metabolic activation)
Positive control substance:
2-acetylaminofluorene
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid

Acetic acid did not show any mutagenic effect under test conditions, with and without metabolic activation.

Conclusions:
Acetic acid did not show any mutagenic effect under test conditions, with and without metabolic activation.
Executive summary:

A bacterial mutagen screening technique was carried out with Acetic acid using Salmonella typhimurium strains S. typhimurium TA 1535, TA 1537, TA 98 and TA 100. The test was performed with and without metabolic activation.

Acetic acid did not show any mutagenic effect under test conditions.

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:
No data on GLP and method (Ames et al. 1975) similar to OECD guideline 471.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(The test was performed only with metabolic activation. No data on positive controls)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
other: Salmonella typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98
Metabolic activation:
with
Metabolic activation system:
S-9 mix
Test concentrations with justification for top dose:
Six concentrations. Maximum dose tested: 40 mg/plate (highest non-cytotoxic dose used in the experiment)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: phosphate buffer
Negative solvent / vehicle controls:
yes
Positive controls:
not specified
Details on test system and experimental conditions:
METHOD OF APPLICATION: Cells cultured overnight were pre-incubated with both the test sample and the S9 mix for 20 minutes at 37 ºC before plating.

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 2 days

NUMBER OF REPLICATIONS: Duplicate plates were used for each of six different concentrations of the sample.


Evaluation criteria:
The result was considered positive if the number of colonies found was twice the number in the control (exposed to the appropriate solvent or untreated).
Key result
Species / strain:
S. typhimurium, other: TA92, TA1535, TA100, TA1537, TA94 and TA98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: Maximum dose tested: 40 mg/plate (highest non-cytotoxic dose used in the experiment)
Vehicle controls validity:
valid
Positive controls validity:
not specified

No significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum dose tested with metabolic activation.

Conclusions:
No significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum dose tested with metabolic activation.
Executive summary:

Reverse mutation assay using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 was carried out with Sodium Acetate according to the method of Ames et al. (1975), but only with metabolic activation.

No significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum dose tested.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
A cytogenetic assay was carried out with Acetic acid using Chinese hamster ovary K1 cells, with and without metabolic activation. In the absence of S9 mix, cells were exposed for 24 h to test substance at doses of 8, 10, 12, 14, and 16 mM. In the presence of S9 mix, cells were exposed for 6 h to test substance at doses of 4, 8, 10, and 12 mM, and recultured in fresh medium for 18 h. The medium used was Ham’s F12 supplemented with 17mM NaHCO3 and 10% fetal calf serum. Cytotoxicity was evaluated by counting surviving cells.
The relationship between the pH of the medium and the clastogenic activity was examined. In order to study the effects of neutralization of the treatment medium, two kinds of treatment media were examined. One was adjusted to pH 5.8 or pH 6.0 and the other was so adjusted and then immediately neutralized to pH 6.4 and pH 7.2 with 1 M NaOH.
GLP compliance:
not specified
Type of assay:
other: in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
K1 cell line
The cells were maintained with Ham's F12 medium (Flow) supplemented with 10 % fetal calf serum, kanamycin (60 µg/mL) and 17 mM sodium bicarbonate. The cells were grown as monolayers at 37 ºC in a 5 % CO2/ 95 % air atmosphere.
The cultures were regularly screened for mycoplasma contamination.
Metabolic activation:
with and without
Metabolic activation system:
S9 (derived from the livers of rats pretreated with phenobarbital and 5,6-benzoflavone)
Test concentrations with justification for top dose:
Without metabolic activation: 8, 10, 12, 14, and 16 mM.
With metabolic activation: 4, 8, 10, and 12 mM.
Vehicle / solvent:
The stock solution of the test compound was prepared in distilled water at 2 M and diluted appropriately with distilled water on the day of use.
Negative solvent / vehicle controls:
yes
Remarks:
(F12 medium)
Positive controls:
no
Details on test system and experimental conditions:
The medium used was Ham’s F12 supplemented with 17mM NaHCO3 and 10% fetal calf serum.

DURATION
- Preincubation period: Cells were cultured for 48 h before the test compound was added. An aliquot of 50-75 µL of diluted acid was added to the culture medium (5 mL).
- In the absence of S9 mix, cells were exposed for 24 h to F12 medium at various pH values.
- In the presence of S9 mx, cells were exposed for 6 h to F12 medium at various pH values and recultured in fresh medium for 18 h.

NUMBER OF REPLICATIONS: At least, two replications.

NUMBER OF CELLS EVALUATED: 100 metaphases/dose/replication.

DETERMINATION OF CYTOTOXICITY
Cytotoxicity was evaluated by counting surviving cells.

In order to study the effects of neutralization of the treatment medium, two kinds of treatment media were examined. One was adjusted to pH 5.8 or pH 6.0 and the other was so adjusted and then immediately neutralized to pH 6.4 and pH 7.2 with 1 M NaOH.

The relationship between the pH of the medium and the clastogenic activity was examined.
The pH of the medium was measured initially and at 6 and 24 h after the treatment.
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(at 16 mM)
Vehicle controls validity:
valid
Positive controls validity:
not examined
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(at 12 mM)
Vehicle controls validity:
valid
Positive controls validity:
not examined
Additional information on results:
Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity.

Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium.

Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity, with and without metabolic activation.

Conclusions:
Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity, with and without metabolic activation.
Executive summary:

A cytogenetic assay was carried out with Acetic acid using Chinese hamster ovary K1 cells, with and without metabolic activation. In the absence of S9 mix, cells were exposed for 24 h to test substance at doses of 8, 10, 12, 14, and 16 mM. In the presence of S9 mix, cells were exposed for 6 h to test substance at doses of 4, 8, 10, and 12 mM, and recultured in fresh medium for 18 h. The medium used was Ham’s F12 supplemented with 17mM NaHCO3 and 10% fetal calf serum. Cytotoxicity was evaluated by counting surviving cells.

The relationship between the pH of the medium and the clastogenic activity was examined. In order to study the effects of neutralization of the treatment medium, two kinds of treatment media were examined. One was adjusted to pH 5.8 or pH 6.0 and the other was so adjusted and then immediately neutralized to pH 6.4 and pH 7.2 with 1 M NaOH.

Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity.

Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
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:
No data on GLP. Method similar to OECD guideline. However, only tests without metabolic activation were carried out and only 100 metaphases were observed.
Principles of method if other than guideline:
Chromosomal aberrations tests were carried out using a Chinese hamster fibroblast cell line, CHL. The cells were exposed to each sample at three different doses for 24 and 48 hours. In the present studies, no metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer.
GLP compliance:
not specified
Type of assay:
other: in vitro mammalian chromosome aberration test
Species / strain / cell type:
other: Chinese hamster fibroblast cell line, CHL
Metabolic activation:
without
Test concentrations with justification for top dose:
Three doses. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. Maximum dose: 1 mg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: physiological saline
Negative solvent / vehicle controls:
yes
Details on test system and experimental conditions:
METHOD OF APPLICATION: Colcemid was added to the culture 2 h before cell harvesting. The cells were then trypsinized and suspended in a hypotonic KCl solution for 13 min at room temperature. After centrifugation the cells were fixed with acetic acid-methanol and spread on clean glass slides.

DURATION
- Exposure duration: 48 h

SPINDLE INHIBITOR (cytogenetic assays): colcemid
STAIN (for cytogenetic assays): Giemsa solution
NUMBER OF CELLS EVALUATED: a hundred well-spread metaphases were observed.


DETERMINATION OF CYTOTOXICITY
- Method: The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer.

OTHER EXAMINATIONS:
- Determination of polyploidy: the incidence of polyploid cells was recorded.
Evaluation criteria:
The results were considered to be negative if the incidence was less than 4.9%, equivocal if it was between 5.0 and 9.9% and positive if it was more than 10%.
Key result
Species / strain:
other: Chinese hamster fibroblast cell line, CHL
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer.
Vehicle controls validity:
valid
Positive controls validity:
not specified

The incidence of cells with aberrations (including gaps) was 0%.

Conclusions:
The incidence of cells with aberrations (including gaps) was 0%.
Executive summary:

Chromosomal aberrations tests were carried out using a Chinese hamster fibroblast cell line, CHL. The cells were exposed to each sample at three different doses for 24 and 48 hours. In the present studies, no metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. The incidence of cells with aberrations (including gaps) was 0%.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 5 to February 27, 2012.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Test method according to OECD Guideline 476. GLP study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
other: mammalian cell gene mutation assay
Target gene:
Thyamidine kinase locus
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
Liver microsome preparations (S9 mix)
Test concentrations with justification for top dose:
Experiment I:
With metabolic activation: 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 9.0 and 10.0 mM
without metabolic activation: 0.1, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0 and 5.5 mM.
Experiment II:
With metabolic activation: 0.1, 0.3, 0.6, 1.2, 2.5, 5.0, 7.5 and 8.5 mM
without metabolic activation: 0.5, 1.0, 2.0, 3.0, 3.5, 4.0, 4.5 and 5.0 mM.

Vehicle / solvent:
- Vehicle(s)/solvent(s) used: RPMI cell culture was used as solvent (RPMI + 5% HS). The pH of cell culture medium as adjusted to physiological range with NaOH. The solvent was compatible with the survival of the cells and the activity of the S9 mix.
Untreated negative controls:
yes
Remarks:
(treatment medium)
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
without metabolic activation
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION:
Short-term exposure (4h): 1x10E+07 cells were suspended in 11 mL RPMI medium with 5% horse serum (25 cm2 flasks) and exposed to designated concentrations of the test item either in the presence of absence of metabolic activation. After exposure, test item was removed by centrifugation (200 x g, 10 min) and the cells were washed twice with PBS. Subsequently the cells were suspended in 30 mL complete culture medium and incubated for an expression and growth period. The cell density was determined each day and adjusted to 3x10E+05 cells/mL in a total culture volume of 20 mL, if necessary.
Long-term exposure (24h): 5x10E+06 cells were suspended in 25 mL RPMI medium with 7.5% horse serum (75 cm2 flasks) and exposed to designated concentrations of the test item in the absence of metabolic activation. After exposure, test item was removed by centrifugation (200 x g, 10 min) and the cells were washed twice with PBS. Subsequently 3x10E+05 cells were suspended in 14 mL complete culture medium and incubated for an expression and growth period. The cell density was determined each day and adjusted to 3x10E+05 cells/mL in a total culture volume of 20 mL, if necessary.
After the expression period cloning efficiency and mutant frequency were analysed (see below).

DURATION
- Exposure duration:
Experiment 1: 4 hours (with and without metabolic activation)
Experiment II: 4 hours (with metabolic acitvation) and 24 hours (without metabolic activation)
- Expression time (cells in growth medium): 2 days, at 37 ºC in 5% Co2/95% humidified air.
- Selection time (if incubation with a selection agent): ~ 14 days at 37 ºC in 5% CO2/95% humidified air

SELECTION AGENT (mutation assays): TFT.

NUMBER OF REPLICATIONS: 1 replicate per dose (negative control, 2 replicates).

NUMBER OF CELLS EVALUATED: 2000 cells/well

DETERMINATION OF CYTOTOXICITY:
Method: Retalive total growth and relative cloning efficiency:
- Relative total growth (RTG): The RTG is the product of the relative suspension growth and the relative cloning efficiency for each culture.
- Suspention growht (SG): The SG reflects the number of times the cell number increases from the starting cell density.
- Cloning efficiency (CE): After the expression period the CE of the cells was determined by seeding a statistical number of 1.6 cells/well in two 96-well plated. The cells were incubated for at least 6 days at 37 ºC in a humidified atmosphere with 5% CO2. Analysis of the results was based on the number of cultures with cell growth (positive wells) and those without cell growth (negative wells) compared to the total number of cultures seeded.
- Mutant frequency: Cultures were seed in selective medium. Cells from each experimental grow were seeded in four 96-well plates and were scored after incubation period. The mutant frequency was calculated dividing the number of TFT resistant colonies by the number of cells plated for selection, corrected for the plating efficiency of cells from the same culture grown in the absence of TFT. The mutant frequencies were compared with the Global Evaluation Factor (GEF= 126).

OTHER EXAMINATIONS:
Clastogenicity: Colony sizing was performed for the highest concentrations of the test item and for the negative and positive controls. Small colonies were defined by slow growth and/or morphological alteration of the cell close.
Evaluation criteria:
The test item is considered mutagenic if following criteria are met: the inducing mutant frequency meets or exceeds the Global Evaluation factor (GEF) of 126 per 10E+06 cells, and a dose-dependent increase in mutant frequency is detected.
Combined with a positive effect in the mutant frequency, an increased occurrence of small colonies (>=40% of total colonies) is an indicative for potential clastogenic effects and/or chromosomal aberrations.
Statistics:
The non-parametric Mann-Whitney test is applied to the mutation data to prove the dose groups for any significant difference in mutant frequency compared to the negative controls.
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: The pH detected with the test item was within the physiological range.
- Water solubility: a solubility test was performed with different solvents and vehicles up to the maximum recommended concentration of 10 mM. Based on the results of the solubility test RPMI cell culture was used as solvent (RPMI + 5% HS). The solvent was compatible with the survival of the cells and the activity of the S9 mix.
- Precipitation: No precipitation of the test item was noted in pre-experiment I and II and experiment I and II with and without metabolic activation.

RANGE-FINDING/SCREENING STUDIES:
Pre-experiment for toxicity: The toxicity of the test item was determined in pre-experiments up to a maximum concentration of 10.0 mM. In pre-experiment I six concentrations [0.1, 0.5, 2.5, 5.0, 7.5 and 10.0 mM] were tested with and without metabolic activation for 4h exposure. In the pre-experiment II (24h long-term exposure without metabolic activation) six concentrations [0.1, 0.5, 1.0, 2.0, 3.0 and 5.0 mM] were tested. The experimental conditions were the same as described below in the experimental performance. In experiment I 10.0 mM (with metabolic activation) and 5.5 mM (without metabolic activation) were selected as the highest concentrations. In experiment II 8.5 mM (with metabolic activation) and 5.0 mM (without metabolic activation were selected as the highest concentrations.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
No toxicity was observed in the pre-experiment I. However, this was not reproducible in the main experiments. In experiment I and II with and without metabolic activation growht inhibition was observed. In experiment I with metabolic activation to relative total growth (RTG) as 23.1% for the highest concentration (10.0 mM) evaluated. The highest concentration evaluated without metabolic activation was 5.5 mM with RTG of 10.1%. In experiment II with metabolic activation the relative total growth (RTG) was 10.5% for the highest concentration (8.5 mM) evaluated. The highest concentration evaluated without metabolic activation was 5.0 with a RTG of 10.3%.

MUTAGENICITY: All dose groups with and without metabolic activation were considered non-mutagenic under test conditions.

Experiment I and II with metabolic activation:

Test Group

Conc. [mM]

RCE [%]

RTG [%]

MF [mutants /106cells]

IMF [mutants /106cells]

GEF exceeded

Statistical significance

Precipitate

C1

0

100.0

100.0

82.0

/

/

/

-

C2

/

/

/

-

2

0.5

95.0

91.4

87.9

5.9

-

-

-

3

1.0

102.1

100.5

91.7

9.7

-

-

-

4

2.0

113.2

114.9

91.0

9.1

-

-

-

5

4.0

91.0

80.4

96.7

14.7

-

-

-

6

6.0

96.4

94.6

104.9

23.0

-

-

-

8

8.0

116.7

77.9

83.7

1.7

-

-

-

9

9.0

106.7

36.6

99.0

17.0

-

-

-

10

10.0

103.6

23.1

153.8

71.8

-

+

-

B[a]P

2.5

77.9

42.1

949.9

867.9

+

+

-

 

Test Group

Conc. [mM]

RCE [%]

RTG [%]

MF [mutants /106cells]

IMF [mutants /106cells]

GEF exceeded

Statistical significance

Precipitate

C1

0

100.0

100.0

82.0

/

/

/

-

C2

/

/

/

-

1

0.1

101.5

89.9

77.1

-4.4

-

-

-

2

0.3

114.5

106.7

79.5

-1.9

-

-

-

3

0.6

97.1

77.7

73.4

-8.1

-

-

-

4

1.2

122.0

107.4

69.0

-12.5

-

-

-

5

2.5

94.3

83.6

73.7

-7.7

-

-

-

6

5.0

106.1

96.0

112.7

31.2

-

-

-

7

7.5

87.8

23.5

90.0

8.5

-

-

-

8

8.5

91.6

10.5

91.7

10.3

-

-

-

B[a]P

3.5

77.2

46.8

601.3

519.9

+

+

-

 

Experiment I and II without metabolic activation:

Test Group

Conc. [mM]

RCE [%]

RTG [%]

MF [mutants /106cells]

IMF [mutants /106cells]

GEF exceeded

Statistical significance

Precipitate

C1

0

100.0

100.0

82.0

/

/

/

-

C2

/

/

/

-

1

0.1

93.4

95.4

97.4

13.2

-

-

-

2

0.5

102.1

108.3

105.5

21.3

-

-

-

3

1.0

93.4

97.7

105.2

21.0

-

-

-

4

2.0

96.2

90.6

115.6

31.4

-

+

-

5

3.0

88.2

60.2

134.9

50.7

-

+

-

6

4.0

92.1

35.1

187.0

102.8

-

+

-

7

5.0

93.4

16.2

177.5

93.3

-

+

-

8

5.5

90.8

10.1

167.1

82.9

-

+

-

EMS

300

70.2

48.8

664.8

580.7

+

+

-

MMS

10

64.5

43.6

531.3

447.2

+

+

-

 

Test Group

Conc. [mM]

RCE [%]

RTG [%]

MF [mutants /106cells]

IMF [mutants /106cells]

GEF exceeded

Statistical significance

Precipitate

C1

0

100.0

100.0

82.0

/

/

/

-

C2

/

/

/

-

5

0.5

109.6

143.6

85.7

11.7

-

-

-

6

1.0

114.6

145.7

98.6

24.6

-

-

-

7

2.0

116.3

148.5

81.3

7.3

-

-

-

8

3.0

109.6

109.6

65.6

-8.3

-

+

-

9

3.5

111.2

85.7

119.9

46.0

-

-

-

10

4.0

112.9

57.0

79.8

5.9

-

-

-

11

4.5

118.1

27.8

66.0

-8.0

-

-

-

12

5.0

97.6

10.3

71.8

-2.1

-

-

-

EMS

200

52.3

33.6

2628.9

2554.9

+

+

-

MMS

10

49.1

35.4

1088.4

1014.5

+

+

-

 

C: Negative controls

RCE: Relative cloning efficiency = [(mean value positive cultures/mean value positive cultures of corresponding controls)*100]

RTG: Relative total growth = (RSG*RCE/100)

MF: Mutant frequency = {-ln [negative cultures/total wells (selected medium)] / -ln [negative cultures/total wells (non selective medium)]}*800

IMF: Induced mutatn frequency = mutant frequency sample – mean value mutant frequency corresponding controls

GEF: Global evaluation factor (126); +: GEF exceeded, -: GEF not exceeded

Statistical significance difference in mutant frequency compared to negative controls (Mann Whitney test, p<0.05). +: signficant; -: not significant.

B[a]P: Benzo[a]pyrene (µg/mL)

EMS: Ethylmethanesulfonate (µg/mL)

MMS: Methylmethanesulfonate (µg/mL)

CLASTOGENICITY: All dose groups with and without metabolic activation were considered as not clastogenic under test conditions.

Main Experiment I and II – Colony sizing, with metabolic activation

 

Test Group

Conc. [mM]

Wells with at least 1 colony

Large colonies

Small colonies

% small colonies

C1

0

45

40

5

11.1

C2

0

45

43

2

4.4

8

8.0

53

48

5

9.8

9

9.0

57

44

13

22.8

10

10.0

83

67

16

19.3

B[a]P

2.5

259

149

110

42.5

 

Test Group

Conc. [mM]

Wells with at least 1 colony

Large colonies

Small colonies

% small colonies

C1

0

49

45

4

8.2

C2

0

46

37

9

19.6

6

5.0

68

59

9

13.2

7

7.5

46

39

7

15.2

8

8.5

49

37

12

24.5

B[a]P

3.5

204

106

98

48.0

 

 

Main Experiment I and II – Colony sizing, without metabolic activation

 

Test Group

Conc. [mM]

Wells with at least 1 colony

Large colonies

Small colonies

% small colonies

C1

0

51

42

9

17.6

C2

0

48

39

6

18.8

6

4.0

96

77

19

19.8

7

5.0

93

86

7

7.5

9

5.5

86

69

17

19.8

MMS

10

166

92

74

44.6

 

Test Group

Conc. [mM]

Wells with at least 1 colony

Large colonies

Small colonies

% small colonies

C1

0

38

30

8

21.1

C2

0

41

34

4

17.1

10

4.0

48

40

8

16.7

11

4.5

42

34

8

19.0

12

5.0

38

33

5

13.2

MMS

10

210

93

117

55.7

Conclusions:
Propyl Triacetoxy Silane (PTA) was considered to be non-mutagenic in the in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells under test conditions.
Executive summary:

The test item Propyl Triacetoxy Silane PTA was assessed for its potential to induce mutations at the mouse lymphoma thyamidine kinase locus using the cell line L5178Y according to OECD Guideline 476.

The selection of the concentrations used in the main experiments was based on data from the toxicity pre-test. The Experiment I was performed as a 4h short-term exposure assay up to 10.0 mM with metabolic activation and up to 5.5 mM without metabolic activation test substance concentration. The Experiment II was performed as a 4h short-term exposure with metabolic activation up to 8.5 mM and as a 24h long-term exposure without metabolic activation up to 5.0 mM test concentration. No precipitation of the test item was noted in pre-experiment I and II and experiment I and II with and without metabolic activation. No toxicity was observed in pre-experiment I. However, this was not confirmed in the main test. In experiment I and II with and without metabolic activation growth inhibition was noted at highest doses. In experiment I and II no biologically relevant increase of mutants was found after treatment with the test item with and without metabolic activation. The Global Evaluation Factor (GEF, defined as the mean of the negative/vehicle mutant frequency plus one standard deviation) was not exceeded by the induced mutant frequency at any concentration. In experiment I without metabolic activation a dose dependent effect was observed. Additionally, in experiment I and II colony sizing showed no clastogenic effects induced by the test item under the experimental conditions (with and without metabolic activation). EMS, MMS and B[a]P were used as positive controls and showed distinct and biologically relevant effects in mutation frequency. Additionally, MMS and B[a]P significantly increased the number of small colonies, thus provind the efficiency of the test system to indicate potential clastogenic effects.

In the described mutagenicity test under the experimental conditions reported, the test item Propyl Triacetoxy Silane PTA is considered to be non-mutagenic in the in vitro mammalian cell gene mutation assay (thymidine kinase locus) in mouse lymphoma L5178Y cells.

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
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid 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: TA 98, TA 100, TA 1535 and TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Based on published experimental data on the supporting substance acetic acid which is considered to be not mutagenic on S. typhimurium TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Conclusions:
Based on published experimental data on the supporting substance acetic acid which is considered to be not mutagenic on S. typhimurium TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Executive summary:

Based on published experimental data on the supporting substance acetic acid which is considered to be not mutagenic on S. typhimurium TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid 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 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Based on published experimental data on the supporting acetic acid which is considered to be not mutagenic on S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 1538, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Conclusions:
Based on published experimental data on the supporting acetic acid which is considered to be not mutagenic on S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 1538, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Executive summary:

Based on published experimental data on the supporting acetic acid which is considered to be not mutagenic on S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 1538, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Species / strain:
S. typhimurium, other: TA 92, TA 1535, TA 100, TA 1537, TA 94 and TA 98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
Based on published experimental data on the supporting substance sodium acetate which is considered to be not mutagenic on S. typhimurium TA 92, TA 1535, TA 100, TA 1537, TA 94, and TA 98, with metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Conclusions:
Based on published experimental data on the supporting substance sodium acetate which is considered to be not mutagenic on S. typhimurium TA 92, TA 1535, TA 100, TA 1537, TA 94, and TA 98, with metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Executive summary:

Based on published experimental data on the supporting substance sodium acetate which is considered to be not mutagenic on S. typhimurium TA 92, TA 1535, TA 100, TA 1537, TA 94, and TA 98, with metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid 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
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
not examined
Additional information on results:
Based on published experimental data on the supporting substance acetic acid which is considered to be not clastogenic on Chinese hamster Ovary (CHO) cells, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not clastogenic under test conditions.
Conclusions:
Based on published experimental data on the supporting substance acetic acid which is considered to be not clastogenic on Chinese hamster Ovary (CHO) cells, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not clastogenic under test conditions.
Executive summary:

Based on published experimental data on the supporting substance acetic acid which is considered to be not clastogenic on Chinese hamster Ovary (CHO) cells, with and without metabolic activation, and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not clastogenic under test conditions.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Species / strain:
other: Chinese hamster fibroblast cell line, CHL
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
Based on published experimental data on the supporting substance sodium acetate which is considered to be not mutagenic on Chinese hamster fibroblast cell line, without metabolic activation (the incidence of cells with aberrations, including gaps, was 0%), and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Conclusions:
Based on published experimental data on the supporting substance sodium acetate which is considered to be not mutagenic on Chinese hamster fibroblast cell line, without metabolic activation (the incidence of cells with aberrations, including gaps, was 0%), and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.
Executive summary:

Based on published experimental data on the supporting substance sodium acetate which is considered to be not mutagenic on Chinese hamster fibroblast cell line, without metabolic activation (the incidence of cells with aberrations, including gaps, was 0%), and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not mutagenic under test conditions.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue Propyltriacetoxysilane which shares the same functional group with Vinyltriacetoxysilane, also has comparable values for the relevant molecular properties for genetic toxicity.
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:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Based on experimental data on analogue substance propyltriacetoxysilane which was considered to be non-mutagenic on mouse lymphoma L5178Y cells with and without activation (no biologically relevant increase of mutants was found after treatment with the test item), and applying the read-across approach, the substance Vinylsilanetriyl triacetate is also considered non-mutagenic under test conditions.
Conclusions:
Based on experimental data on analogue substance propyltriacetoxysilane which was considered to be non-mutagenic on mouse lymphoma L5178Y cells with and without activation (no biologically relevant increase of mutants was found after treatment with the test item), and applying the read-across approach, the substance Vinylsilanetriyl triacetate is also considered non-mutagenic under test conditions.
Executive summary:

A mammalian cell gene mutation assay was performed with mouse lymphoma L5178Y cells on analogue Propyltriacetoxysilane according to OECD Guideline 476. No biologically relevant increase of mutants was found after treatment with test item in both experiments, I (up to 10.0 mM with metabolic activation for 4h exposure and up to 5.5 mM without metabolic activation for 4h exposure) and II (up to 8.5 mM with metabolic activation for 4h exposure and up to 5.0 mM without metabolic activation for 24h exposure). Based on these results, the read-across approach was applied and the substance Vinyltriacetoxysilane was considered to be non-mutagenic on mouse lymphoma L5178Y cells with and without metabolic activation under test conditions.

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

Genetic toxicity in vivo

Description of key information

Key study: Based on experimental results with supporting substance sodium acetate, read-across approach was applied and the in vivo genetic toxicity for triacetoxyvinylsilane is also considered negative (no inhibitory effects on DNA-replication detectable).

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
This is not a standard genotoxicity test system, but it provides evidence that acetic acid, sodium salt is not genotoxic in animals.
Principles of method if other than guideline:
This is not a routine genotoxicity test system. Method: 3H-thymidine incorporation measured.
GLP compliance:
no
Type of assay:
other: Testicular DNA-synthesis inhibition test (DSI test)
Species:
mouse
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 25-30 g
Route of administration:
oral: gavage
Duration of treatment / exposure:
A single administration.
Frequency of treatment:
A single administration.
Dose / conc.:
200 mg/kg bw (total dose)
Remarks:
Basis: nominal conc.
Dose / conc.:
500 mg/kg bw (total dose)
Remarks:
Basis: nominal conc.
Dose / conc.:
1 000 mg/kg bw (total dose)
Remarks:
Basis: nominal conc.
No. of animals per sex per dose:
No data on number of animals.
Control animals:
yes
Positive control(s):
No data.
Tissues and cell types examined:
3H-thymidine incorporation in testicular cells.
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
No inhibitory effect on DNA-replication was detectable.
Conclusions:
No inhibitory effect on DNA-replication was detectable in animals treated with Sodium Acetate.
Executive summary:

The Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice with Sodium Acetate. This is not a standard genotoxicity test system, but it provides evidence that acetic acid, sodium salt is not genotoxic in animals. The basis of the method is to measure 3H-thymidine incorporation. Animals receive a single oral dose by gavage at concentration of 200, 500 and 1000 mg/kg bw of test substance.

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
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
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
Based on experimental results with supporting substance sodium acetate, read-across approach was applied and no inhibitory effects on DNA-replication was detectable in animals treated with triacetoxyvinylsilane.
Conclusions:
Based on experimental results with supporting substance sodium acetate, read-across approach was applied and no inhibitory effects on DNA-replication was detectable in animals treated with triacetoxyvinylsilane.
Executive summary:

Based on experimental results with supporting substance sodium acetate, read-across approach was applied and the in vivo genetic toxicity for triacetoxyvinylsilane is also considered negative (no inhibitory effects on DNA-replication detectable).

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

Additional information

Read-across from experimental results with supporting substances acetic acid and sodium acetate:

In vitro gene mutation in bacteria: Weight of evidence:

  

In the study by Zeiger et. al., 1992 (reliability 1), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 and with GLP compliance was performed. A standard Ames test was carried out with acetic acid using Salmonella typhimurium strains TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and triacetoxyvinylsilane was also considered as no mutagenic under test conditions.

 

In the study by McMahon et. al., 1979 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. A bacterial mutagen screening technique was carried out with acetic acid using Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and triacetoxyvinylsilane was also considered as no mutagenic under test conditions.

 

In the study by Ishidate et. al., 1984 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. The study was carried out with sodium acetate and using Salmonella typhimurium strains TA92, TA1535, TA100, TA1537, TA94, only with metabolic activation. No significant increases in the numbers of revertant colonies were detected at the maximum dose tested. Based on these experimental results, read-across approach was applied and triacetoxyvinylsilane was also considered as no mutagenic under test conditions.

 

In vitro mammalian chromosome aberration. Weight of evidence:

 

In the study by Morita et. al., 1990 (reliability 2), a cytogenetic assay was carried out with acetic acid using Chinese hamster ovary K1 cells. Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity, both with and without metabolic activation. Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium. Based on these experimental results and applying the read-across approach, the substance triacetoxyvinylsilane is also considered as not clastogenic under test conditions.

 

In the study by Ishidate et. al., 1983 (reliability 2), a chromosomal aberrations tests were carried out with sodium acetate using a Chinese hamster fibroblast cell line. In the studies, no metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. The incidence of cells with aberrations (including gaps) was 0%. Based on these experimental results, the read-across approach was applied and triacetoxyvinylsilane was also considered as no mutagenic under test conditions.

Read-across from experimental results with analogue substance Propyltriacetoxysilane:

In vitro gene mutation in mammalian cells. Key study:

A mammalian cell gene mutation assay was performed with mouse lymphoma L5178Y cells on analogue Propyltriacetoxysilane according to OECD Guideline 476. No biologically relevant increase of mutants was found after treatment with test item in both experiments, I (up to 10.0 mM with metabolic activation for 4h exposure and up to 5.5 mM without metabolic activation for 4h exposure) and II (up to 8.5 mM with metabolic activation for 4h exposure and up to 5.0 mM without metabolic activation for 24h exposure). Based on these results, the read-across approach was applied and the substance Vinyltriacetoxysilane was considered to be non-mutagenic on mouse lymphoma L5178Y cells with and without metabolic activation under test conditions.

Read-across from experimental results with supporting substance sodium acetate:

In vivo genetic toxicity. Key study:

In the study by Seiler, 1981 (reliability 2), the Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice with sodium acetate (single oral dose by gavage). No inhibitory effect on DNA-replication was detectable in animals treated with sodium acetate. Based on these results, read-across approach was applied and triacetoxyvinylsilane is also considered no genotoxic in animals (based on no effects on DNA-replication).

Justification for classification or non-classification

Based on the available information on genetic toxicity in vitro (Bacterial Reverse Mutation Assay, Chromosome Aberration and Gene Mutation Tests) and in vivo (DNA damage genotoxicity test) the substance triacetoxyvinylsilane is considered to be negative, and therefore, the substance is not classified according to CLP Regulation.