A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 10, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to EU Method C.7, with GLP.

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: the concentrations of the 3 main components of the test substance were determined at the earliest possible time, i.e. 0.75 h after the start of the dissolution. Later sampling times were not required as the concentrations were already below the limit of quantification at 0.75 h.

Buffers:

Buffer pH 4:
- pH (actual pH preliminary test): 4.0
- Composition of buffer: 250 mL 0.1 mol/L potassium dihydrogencitrate (Fluka; Lot. No. 364546/1) and 45 mL 0.1 mol/L sodium hydroxide (Titrisol; Merck, Lot. No. OC489094) filled up to 500 mL with water.

Buffer pH 7:
- pH (actual pH preliminary test): 7.0
- Composition of buffer: 250 mL 0.1 mol/L potassium dihydrogenphosphate (Merck, Lot. No. A531473427) and 148.2 mL 0.1 mol/L sodium hydroxide filled up to 500 mL with water.

Buffer pH 9:
- pH (actual pH preliminary test): 9.0
- Composition of buffer: 250 mL 0.1 mol/l boric acid (Merck, Lot. No. K20380665) in 0.1 mol/L potassium chloride (Merck, Lot. No. K31517236313) and 106.5 mL 0.1 mol/L sodium hydroxide filled up to 500 mL with water.

The water (for analysis) Merck Lot. No. OC409681 was autoclaved before use.

Duration:

0.75 h

pH:

4.02

Temp.:

25 °C

Initial conc. measured:

9.41 mg/L

Duration:

0.75 h

pH:

7.01

Temp.:

25 °C

Initial conc. measured:

10.34 mg/L

Duration:

0.75 h

pH:

8.98

Temp.:

25 °C

Initial conc. measured:

9.78 mg/L

Number of replicates:

There were no replicates

Positive controls:

no

Negative controls:

no

Preliminary study:

The preliminary test indicated that the half-lifes of the 3 main components of the test substance at 25 °C and at pH 4, pH 7 and pH 9 are shorter than 1 hour in each case. Therefore the test substance is considered to be easily hydrolysable and no main test was performed, according to the guideline.

Test performance:

The concentrations of the 3 main components of the reaction mass were determined at the earliest possible time, i.e. 0.75 h after the start of the dissolution. Later sampling times were not required as the concentrations were already below the limit of quantification at 0.75 h.

Transformation products:

no

Details on hydrolysis and appearance of transformation product(s):

The test substance is composed of several compounds, including the 3 main components acetone O,O'-[methoxy(vinyl)silanediyl]oxime; acetone O,O',O''-(vinylsilanetriyl)oxime and acetone O-[dimethoxy(vinyl)silyl]oxime . They polymerise, triggered by hydrolysis.

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetoneO,O',O''-(vinylsilanetriyl)oxime

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetoneO,O',O''-(vinylsilanetriyl)oxime

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetoneO,O',O''-(vinylsilanetriyl)oxime

Other kinetic parameters:

No kinetic of the hydrolysis could be determined because of the slow dissolution of the test substance and the fast hydrolysis.

Rate constants of hydrolysis and half life times

pH	temperature (°C)	rate constant (h^-1)	rate constant (s^-1)	half life (h)
4	25	>1	>0.0003	<1
7	25	>1	>0.0003	<1
9	25	>1	>0.0003	<1

Results of the hydrolysis at 25 °C, pH = 4 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	4.02	9.41*	/
0.75	4.02	< 3.78 **	>55

Results of the hydrolysis at 25 °C, pH = 7 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	7.01	10.34 *	/
0.75	7.01	< 3.78 **	>55

Results of the hydrolysis at 25 °C, pH = 9 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	8.98	9.78 *	/
0.75	8.98	< 3.78 **	>55

* Concentration calculated from the nominal initial concentration of the test substance and the content of the component.

** Below the limit of quantification.

Validity criteria fulfilled:

yes

Conclusions:

The analysed concentration of acetone O,O',O''-(vinylsilanetriyl)oxime was below the limit of quantification (0.94 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

Executive summary:

The hydrolysis as a function of pH study was carried out for the test substance.This test material is composed of several compounds, including the 3 main components acetoneO,O'-[methoxy(vinyl)silanediyl]oxime; acetoneO,O',O''-(vinylsilanetriyl)oxime and acetoneO-[dimethoxy(vinyl)silyl]oxime. They polymerise, triggered by hydrolysis. The rate constants of hydrolysis and half-life times of the 3 main components were determined at pH 4, pH 7 and pH 9. Due to the predicted instability of the test substance, the test was performed at 25 °C and not at 50 °C as described in the guideline for the "preliminary test".

For the acetoneO,O',O''-(vinylsilanetriyl)oxime a component of the test substance, no "main test" was performed as the half-life time was < 1 h. The analysed concentration by gas chromatography, was below the limit of quantification (0.94 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

acetoneO,O',O''-(vinylsilanetriyl)oxime, one of the main components of the test substanceis easily hydrolysable at each of the pH's tested.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 10, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to EU Method C.7, with GLP.

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: the concentrations of the 3 main components of the test substance were determined at the earliest possible time, i.e. 0.75 h after the start of the dissolution. Later sampling times were not required as the concentrations were already below the limit of quantification at 0.75 h.

Buffers:

Buffer pH 4:
- pH (actual pH preliminary test): 4.0
- Composition of buffer: 250 mL 0.1 mol/L potassium dihydrogencitrate (Fluka; Lot. No. 364546/1) and 45 mL 0.1 mol/L sodium hydroxide (Titrisol; Merck, Lot. No. OC489094) filled up to 500 mL with water.

Buffer pH 7:
- pH (actual pH preliminary test): 7.0
- Composition of buffer: 250 mL 0.1 mol/L potassium dihydrogenphosphate (Merck, Lot. No. A531473427) and 148.2 mL 0.1 mol/L sodium hydroxide filled up to 500 mL with water.

Buffer pH 9:
- pH (actual pH preliminary test): 9.0
- Composition of buffer: 250 mL 0.1 mol/l boric acid (Merck, Lot. No. K20380665) in 0.1 mol/L potassium chloride (Merck, Lot. No. K31517236313) and 106.5 mL 0.1 mol/L sodium hydroxide filled up to 500 mL with water.

The water (for analysis) Merck Lot. No. OC409681 was autoclaved before use.

Duration:

0.75 h

pH:

4.02

Temp.:

25 °C

Initial conc. measured:

8.05 mg/L

Duration:

0.75 h

pH:

7.01

Temp.:

25 °C

Initial conc. measured:

8.84 mg/L

Duration:

0.75 h

pH:

8.98

Temp.:

25 °C

Initial conc. measured:

8.36 mg/L

Number of replicates:

There were no replicates

Positive controls:

no

Negative controls:

no

Preliminary study:

The preliminary test indicated that the half-lifes of the 3 main components of the test substance at 25 °C and at pH 4, pH 7 and pH 9 are shorter than 1 hour in each case. Therefore the test substance is considered to be easily hydrolysable and no main test was performed, according to the guideline.

Test performance:

The concentrations of the 3 main components of "Wasox-VMAC2" were determined at the earliest possible time, i.e. 0.75 h after the start of the dissolution. Later sampling times were not required as the concentrations were already below the limit of quantification at 0.75 h.

Transformation products:

no

Details on hydrolysis and appearance of transformation product(s):

The test substance is composed of several compounds, including the 3 main components acetone O,O'-[methoxy(vinyl)silanediyl]oxime; acetone O,O',O''-(vinylsilanetriyl)oxime and acetone O-[dimethoxy(vinyl)silyl]oxime. They polymerise, triggered by hydrolysis.

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetone O-[dimethoxy(vinyl)silyl]oxime

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetone O-[dimethoxy(vinyl)silyl]oxime

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetone O-[dimethoxy(vinyl)silyl]oxime

Other kinetic parameters:

No kinetic of the hydrolysis could be determined because of the slow dissolution of the test substance and the fast hydrolysis.

Rate constants of hydrolysis and half life times

pH	temperature (°C)	rate constant (h^-1)	rate constant (s^-1)	half life (h)
4	25	>1	>0.0003	<1
7	25	>1	>0.0003	<1
9	25	>1	>0.0003	<1

VM2AC: Results of the hydrolysis at 25 °C, pH = 4 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	4.02	8.05 *	/
0.75	4.02	< 0.64 **	>90

Results of the hydrolysis at 25 °C, pH = 7 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	7.01	8.84 *	/
0.75	7.01	< 0.64 **	>90

Results of the hydrolysis at 25 °C, pH = 9 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	8.98	8.36 *	/
0.75	8.98	< 0.64 **	>90

* Concentration calculated from the nominal initial concentration of the test substance and the content of the component.

** Below the limit of quantification.

Validity criteria fulfilled:

yes

Conclusions:

The analysed concentration of the acetone O-[dimethoxy(vinyl)silyl]oxime was below the limit of quantification (0.16 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

Executive summary:

The hydrolysis as a function of pH study was carried out for the test substance.This test material is composed of several compounds, including the 3 main components. They polymerise, triggered by hydrolysis. The rate constants of hydrolysis and half-life times of the 3 main components were determined at pH 4, pH 7 and pH 9. Due to the predicted instability of the test substance, the test was performed at 25 °C and not at 50 °C as described in the guideline for the "preliminary test".

For acetoneO-[dimethoxy(vinyl)silyl]oxime, component of the reaction mass, no "main test" was performed as the half-life time was < 1 h.The analyzed concentration by gas chromatography, was below the limit of quantification (0.16 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

AcetoneO-[dimethoxy(vinyl)silyl]oxime, one of the main component of the test materials easily hydrolysable at each of the pH's tested.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 10, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to EU Method C.7, with GLP

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: the concentrations of the 3 main components of the test substance were determined at the earliest possible time, i.e. 0.75 h after the start of the dissolution. Later sampling times were not required as the concentrations were already below the limit of quantification at 0.75 h.

Buffers:

Buffer pH 4:
- pH (actual pH preliminary test): 4.0
- Composition of buffer: 250 mL 0.1 mol/L potassium dihydrogencitrate (Fluka; Lot. No. 364546/1) and 45 mL 0.1 mol/L sodium hydroxide (Titrisol; Merck, Lot. No. OC489094) filled up to 500 mL with water.

Buffer pH 7:
- pH (actual pH preliminary test): 7.0
- Composition of buffer: 250 mL 0.1 mol/L potassium dihydrogenphosphate (Merck, Lot. No. A531473427) and 148.2 mL 0.1 mol/L sodium hydroxide filled up to 500 mL with water.

Buffer pH 9:
- pH (actual pH preliminary test): 9.0
- Composition of buffer: 250 mL 0.1 mol/l boric acid (Merck, Lot. No. K20380665) in 0.1 mol/L potassium chloride (Merck, Lot. No. K31517236313) and 106.5 mL 0.1 mol/L sodium hydroxide filled up to 500 mL with water.

The water (for analysis) Merck Lot. No. OC409681 was autoclaved before use.

Duration:

0.75 h

pH:

4.02

Temp.:

25 °C

Initial conc. measured:

26.01 mg/L

Duration:

0.75 h

pH:

7.01

Temp.:

25 °C

Initial conc. measured:

28.58 mg/L

Duration:

0.75 h

pH:

8.98

Temp.:

25 °C

Initial conc. measured:

27.04 mg/L

Number of replicates:

There were no replicates.

Positive controls:

no

Negative controls:

no

Preliminary study:

The preliminary test indicated that the half-lifes of the 3 main components of the test substance at 25 °C and at pH 4, pH 7 and pH 9 are shorter than 1 hour in each case. Therefore the test substance is considered to be easily hydrolysable and no main test was performed, according to the guideline.

Test performance:

The concentrations of the 3 main components of the test substance were determined at the earliest possible time, i.e. 0.75 h after the start of the dissolution. Later sampling times were not required as the concentrations were already below the limit of quantification at 0.75 h.

Transformation products:

no

Details on hydrolysis and appearance of transformation product(s):

The test substance is composed of several compounds, including the 3 main components. They polymerise, triggered by hydrolysis.

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetone O,O'-[methoxy(vinyl)silanediyl]oxime

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetone O,O'-[methoxy(vinyl)silanediyl]oxime

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

> 1 h-1

DT50:

< 1 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: acetone O,O'-[methoxy(vinyl)silanediyl]oxime

Other kinetic parameters:

No kinetic of the hydrolysis could be determined because of the slow dissolution of the test substance and the fast hydrolysis.

Rate constants of hydrolysis and half life times

pH	temperature (°C)	rate constant (h^-1)	rate constant (s^-1)	half life (h)
4	25	>1	>0.0003	<1
7	25	>1	>0.0003	<1
9	25	>1	>0.0003	<1

Results of the hydrolysis at 25 °C, pH = 4 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	4.02	26.01 *	/
0.75	4.02	< 4.18 **	>80

Results of the hydrolysis at 25 °C, pH = 7 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	7.01	28.58 *	/
0.75	7.01	< 4.18 **	>80

Results of the hydrolysis at 25 °C, pH = 9 (preliminary test)

time of exposure [h]	pH	concentration [mg/L]	decrease of the initial concentr. [%]
0	8.98	27.04 *	/
0.75	8.98	< 4.18 **	>80

* Concentration calculated from the nominal initial concentration of the test substance and the content of the component.

** Below the limit of quantification.

Validity criteria fulfilled:

yes

Conclusions:

The acetone O,O'-[methoxy(vinyl)silanediyl]oxime concentration was below the limit of quantification (1.04 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this componenet at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

Executive summary:

The hydrolysis as a function of pH study was carried out for the test substance. This test material is composed of several compounds, including the 3 main components acetone O,O'-[methoxy(vinyl)silanediyl]oxime; acetone O,O',O''-(vinylsilanetriyl)oxime and acetone O-[dimethoxy(vinyl)silyl]oxime. They polymerise, triggered by hydrolysis. The rate constants of hydrolysis and half-life times of the 3 main components were determined at pH 4, pH 7 and pH 9. Due to the predicted instability of the test substance, the test was performed at 25 °C and not at 50 °C as described in the guideline for the "preliminary test".

For the main component of the reaction mass, no "main test" was performed as the half-life time was < 1 h. The analysed concentration of acetoneO,O'-[methoxy(vinyl)silanediyl]oxime by gas chromatography, was below the limit of quantification (1.04 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

AcetoneO,O'-[methoxy(vinyl)silanediyl]oxime, the main component of the test substance(range: 45-70% w/w) is easily hydrolysable at each of the pH's tested.

Reference 4

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Principles of method if other than guideline:

- Principle of test: The purpose of the study was to develop an appropriate analytical method for the quantitative determination of the test item in samples originated from hydrolysis studies.
- Short description of test conditions: The hydrolysis assessment was performed at pH 1.2, 4, 7 and 9.

GLP compliance:

not specified

Remarks:

No information provided

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Buffer pH 1.2:
- Composition of buffer: 26.4 g KH2PO4 was dissolved in 2 L HPLC water and the pH was set to 1.2 with cc. phosphoric acid.

Buffer pH 4:
- Composition of buffer: 13.6 g KH2PO4 was dissolved in 1 L HPLC water and the pH was set to 4 with cc. phosphoric acid.

Buffer pH 7:
- Composition of buffer: 13.6 g KH2PO4 was dissolved in 1 L HPLC water and the pH was set to 7 with 1 M KOH solution.

Buffer pH 9:
- Composition of buffer: 13.0 g KH2PO4 was dissolved in 1 L HPLC water and the pH was set to 9 with 1 M KOH solution.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used:
Stock Solution in Tetrahydrofuran: Approx. 30 mg test item was measured into 5 mL volumetric flask and filled up with tetrahydrofuran (ca. 6 mg/mL concentration).
Test Solution: 50 μL aliquots of Stock Solution in Tetrahydrofuran were added to 100 mL buffer solutions. The spiked solutions were mixed at 20 and 37°C and extracted after 1 and 2 hours.

Duration:

1 h

pH:

1.2

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

1 h

pH:

1.2

Temp.:

37 °C

Initial conc. measured:

3 mg/L

Duration:

2 h

pH:

1.2

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

2 h

pH:

1.2

Temp.:

37 °C

Initial conc. measured:

3 mg/L

Duration:

1 h

pH:

4

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

2 h

pH:

4

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

1 h

pH:

7

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

2 h

pH:

7

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

1 h

pH:

9

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Duration:

2 h

pH:

9

Temp.:

20 °C

Initial conc. measured:

3 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

yes

Test performance:

The different pH buffer solutions (1.2, 4, 7 and 9) were spiked with the stock solution of the test item and kept at 20 and 37°C. After the applied liquid – liquid extraction method (100x enrichment) no test item components were found in the heptanic phases.

Transformation products:

not measured

Key result

pH:

1.2

Temp.:

20 °C

DT50:

< 1 h

Remarks on result:

other: According to the measured results the test item totally hydrolysed after 1 hour

Key result

pH:

1.2

Temp.:

37 °C

DT50:

< 1 h

Remarks on result:

other: According to the measured results the test item totally hydrolysed after 1 hour

Key result

pH:

4

Temp.:

20 °C

DT50:

< 1 h

Remarks on result:

other: According to the measured results the test item totally hydrolysed after 1 hour

Key result

pH:

7

Temp.:

20 °C

DT50:

< 1 h

Remarks on result:

other: According to the measured results the test item totally hydrolysed after 1 hour

Key result

pH:

9

Temp.:

20 °C

DT50:

< 1 h

Remarks on result:

other: According to the measured results the test item totally hydrolysed after 1 hour

Validity criteria fulfilled:

yes

Conclusions:

According to the measured results the test item totally hydrolysed after 1 hour under all the examined conditions.

Executive summary:

An hydrolysis assessment was performed for test substance Wasox-VMAC2 with a developed analytical method based on GC-FID at pH 1.2, 4, 7 and 9. The applied analytical method was linear in the 0.03 – 0.4 mg/mL concentration range. The different pH buffer solutions (1.2, 4, 7 and 9) were spiked with the stock solution of the test item and kept at 20 and 37°C. After the applied liquid – liquid extraction method

(100x enrichment) no test item components were found in the heptanic phases. According to the measured results the test item totally hydrolysed after 1 hour under all the examined conditions. Due to the fast hydrolysis even at 20°C the Tier 1 and Tier 2 of the OECD 111 guide is not applicable for the test item.

Reference 5

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

Tier 3

GLP compliance:

not specified

Remarks:

No information provided

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Buffer pH 1.2:
- Composition of buffer: 44.6 mg KCl (Merck, A6670333 524) was dissolved in 4.00 ml D2O, and the pD value was set by small volume of 1:1 DCl solution (Sigma-Aldrich, LOT#: EB0578V). The final pD value was read to 0.78 so the pH was 1.20.

Buffer pH 4:
- Composition of buffer: 122.9 mg potassium hydrogen phthalate (Reanal, LOT#:826685) was dissolved in 4.00 ml D2O and the pD was set by adding a small amount of DCl solution. The final pD value was read to 3.64 so the pH was 4.08.

Buffer pH 7:
- Composition of buffer: 37.4 mg KH2PO4 (Reanal, LOT#: 82051593) was dissolved in 4.00 ml D2O, and the pD value was set by addition of 1:1 dilution of concentrated NaOD solution (Alfa-Aesar LOT#:Q64D040). The final pD value was read to 6.64, so the pH was 7.06.

Buffer pH 9:
- Composition of buffer: 37.4 mg boric acid (Acidum) was dissolved in 4.00 ml D2O and the pD value was set by addition of 1:1 dilution of concentrated NaOD solution. The final pD value was read to 8.51, so the pH was 8.93.

Note: As the solutions were made with D2O the instrument reads the pD value of the samples, therefore the readouts were converted to pH according to the following known equation: pH = pD + 0.415

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used:
Approximately 0.01 M solution of the test item was prepared in buffers deoxygenated (by bubbling nitrogen through the buffers) as recommended in the OECD 111 guide.
The buffer solutions were prepared using D2O (Eurisotop. LOT# M3301), with 0.005M TSP standard (sodium salt of 3-(Trimethylsilyl)propionic-2,2,3,3-d4 acid, Cambridge Isotope Laboratories, LOT#: I1-7117; 86.1mg TSP was diluted to 100.00ml with D2O).
The pH was measured with a Metrohm 736GP Titrino system equipped with Metrohm 6.01234.100 combined glass electrode. The electrode was calibrated at 25.0±0.1oC with a 0.05M potassium hydrogen phthalate solution (pH=4.005) and the slope was set to 1.000.

Number of replicates:

1

Positive controls:

no

Negative controls:

no

Statistical methods:

TopSpin 2.1 software package was used for the acquisition, while the evaluation of the recorded spectra was carried out with MestreNova 8.

Preliminary study:

Results of the preliminary tests clearly indicated very fast hydrolysis, fast liberation of the acetone oxime and methanol as well as immediate condensation to form highly cross-linked high molecular weight polymers.

Test performance:

The formation of hydrolysis products methanol and acetone oxime was demonstrated. Also a gel phase was formed at each pH value. After 1H-NMR anlysis It was confirmed that this precipitate contains vinyl moieties in various chemical environment.

Transformation products:

yes

No.:

#1

No.:

#2

Details on hydrolysis and appearance of transformation product(s):

- Formation and decline of each transformation product during test:
At first stage, three different samples composed of Wasox VMAC2 (W1A*) + acetoxime, Wasox VMAC2 (W1AM**) + acetoxime + methanol and Wasox VMAC2 + 2 acetoxime (W1AA***), were tested at pH= 1.2 to demostrate the formation of methanol and acetone oxime. It was clearly seen, that upon addition of methanol the peak at 3.36 ppm (previously confirmed to correspond to methanol) increases compared to the original sample, while the additional acetoxime solution increases the peak at 1.90 ppm (previously confirmed to correspond to acetoxime). See table 1.

In the main study, comparison of the NMR spectra of the Wasox VMAC2 samples hydrolyzed at different pH values with the previously obtained NMR spectra of methanol and acetoxime in D2O , shows that it is visible that at all pH values acetoxime and methanol are the only soluble hydrolysis products. It was observed that a gel is also formed at each pH values. See figure below and tables 2 and 3.

Key result

Remarks on result:

other: Due to the fast kinetics of the hydrolysis of the test item a detailed determination of the hydrolysis rate is not possible with common analytical methods.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Different tested pH has no effect on the chemical shifts of the methyl group of methanol. The methyl peaks are visible the same position regardless of the media pH values. In the acetoxime proton NMR spectra was found that at pH:1.2 the chemical shift of the methyl groups of acetoxime appears at higher position (2.1 ppm) than in the other spectra. The chemical shift is changing at lower pH, but it can be seen that the other spectra are the same.
- Anomalies or problems encountered (if yes): a gel phase was formed at each pH value. Further analysis of this gel was conducted as explained below.

MAJOR TRANSFORMATION PRODUCTS
The preliminary studies on the test item showed, that the average value of acetoxime group is 2 in the molecule, while integrals showed 1 methoxy function average per molecule. Taking the initial 0.01M concentration of the test item into account, and assuming that structure of main component acetone O,O'-[methoxy(vinyl)silanediyl]oxime (VMAC2) is the best average representation of the three different forms the completely hydrolyzed sample should theoretically contain 10 mM methanol and 20 mM acetone oxime.


SUPPLEMENTARY EXPERIMENT (if any): RESULTS:
The gel formed a thin layer on the inside wall of the glass vials at each pH. As this gel acts like a solid material in NMR point of view (fast relaxation), it was necessary to dissolve it to get useful NMR signals.
In the preliminary experiments it was found that it can be dissolved in strongly alkaline media (2M NaOH). To collect enough gel for the study 100.00 ml solution at 0.01M concentration level was prepared at each pH, and hydrolysed with ditilled water according to the protocol used for the D2O samples. At the end of the procedure the solution was filtered with a 0.20 μm membrane filter, and after it was washed with 10 ml 2M NaOH solution. The alkaline solution passing through the membrane was collected. The basic solution was introduced to the reaction vessel again and kept in the flask for 48 h at 25ºC with continuous shaking, to remove as much gel precipitate from the wall as it was possible. After 48 h the water from solution was evaporated at 80ºC. The remaining solid residue was dissolved in 2.00 ml D2O (containing TSP). 600 μl sample was transferred into an NMR tube, and 1H NMR spectrum was recorded.

The spectra show high similarity. It was found that the solution contains vinyl moieties in various chemical environment. Any other oligomers aggregates were observed at any pH tested.

Table 1: Integral values of the given groups at pH 1.2

Sample code	Integral of acetoxime	Integral of methanol
W1A*	2.39	0.59
W1AM**	2.32	1.23
W1AA***	4.98	0.59

*Wasox VMAC2 + acetoxime **Wasox VMAC2 + acetoxime + methanol ***Wasox VMAC2 + 2 acetoxime

Table 2: Integral values and concentrations (mM) of hydrolysates at different pH

pH	methanol		acetoxime		vinyl group
	intensity	concentration (mM)	intensity	concentration (mM)	intensity	concentration (mM)
1.2	0.60	9.3	2.39	18.0	0.57	8.8
4.0	0.50	7.7	2.66	20.0	0.39	6.0
7.0	0.50	7.7	2.63	19.8	0.38	5.9
9.0	0.46	7.1	2.56	19.2	0.33	5.1

Table 3: Integral values and concentrations (mg/ml) of hydrolysates at different pH

pH	methanol		acetoxime		vinyl group
	intensity	concentration (mg/ml)	intensity	concentration (mg/ml)	intensity	concentration (mg/ml)
1.2	0.60	0.3	2.39	1.3	0.57	0.2
4.0	0.50	0.2	2.66	1.5	0.39	0.2
7.0	0.50	0.2	2.63	1.4	0.38	0.2
9.0	0.46	0.2	2.56	1.4	0.33	0.1

* the concentration of the vinyl group was calculated from the methanol calibration, as the vinyl and methyl groups contain the same amount of protons

Validity criteria fulfilled:

yes

Conclusions:

In a tier 3 hydrolysis study of Wasox-VMAC2 the formation of hydrolysis products methanol and acetone oxime was demonstrated. Also a gel phase was formed at each pH value. After 1H-NMR analysis, it was confirmed that this precipitate contains vinyl moieties in various chemical environment.

Executive summary:

An hydrolysis assessment of Wasox VMAC2 was performed according to Tier 3 of the OECD 111 guideline. The hydrolysis behaviour of the test item was examined at pH values normally found in the environment (pH 4 to 9) and under more acidic conditions (pH 1) for physiological purposes. Results of the preliminary tests clearly indicated very fast hydrolysis, fast liberation of the acetone oxime and methanol as well as immediate condensation to form highly cross-linked high molecular weight polymers. The identification of the test item as well as of the proposed main degradation products acetoxime and methanol was accomplished by means of 1H NMR spectroscopy. During the main assay it was confirmed that at all pH values acetoxime and methanol are the only soluble hydrolysis products. Also, it was observed that a gel was formed at each pH values. The hydrolysis to acetoxime is almost 100% percent regardless of the pH. Its concentration can be considered the same at slightly acidic, neutral or basic media (pH 4-9), however at more acidic conditions the hydrolysis to acetoxime is a little bit suppressed. The formation of methanol is more pronounced under acidic conditions. When increasing the pH, the signal intensity of the soluble molecules containing vinyl group decreases. If all of the vinyl moieties remained in the solution, 10 mM concentration would be expected, but not at all pH values which means that during gel formation vinyl containing sylanol macro molecules are produced. The gel was not visible directly by NMR, but by basic digestion the polymer chains could be broken and taken to solution where the signals of the gel became visible. All the proton peaks detected from the digested gel samples fall into the chemical shift region where the vinyl-group signals are expected. The signal showed complicated pattern. The most plausible reason for this is the different length of the siloxane oligomer chains that form during dissolution of the gel.

Description of key information

Key study: preliminary test with Wasox-VMAC2: According to the measured results the test item totally hydrolysed after 1 hour under all the examined conditions.

Key study: Tier 3 study with Wasox-VMAC2: The formation of hydrolysis products methanol and acetone oxime was demonstrated. Also a gel phase was formed at each pH value. After 1H-NMR analysis, it was confirmed that this precipitate contains vinyl moieties in various chemical environment.

Key study: Hydrolysis of main components of Wasox-VMAC2: The hydrolysis as a function of pH study was carried out for the 3 main components acetone O,O'-[methoxy(vinyl)silanediyl]oxime; acetone O,O',O''-(vinylsilanetriyl)oxime and acetone O-[dimethoxy(vinyl)silyl]oxime. They polymerise, triggered by hydrolysis.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 h

at the temperature of:

20 °C

Additional information

Key study: preliminary test with Wasox-VMAC2: An hydrolysis assessment was performed for test substance Wasox-VMAC2 with a developed analytical method based on GC-FID at pH 1.2, 4, 7 and 9. After the applied liquid – liquid extraction method (100x enrichment) no test item components were found in the heptanic phases. According to the measured results the test item totally hydrolysed after 1 hour under all the examined conditions. Due to the fast hydrolysis even at 20°C the Tier 1 and Tier 2 of the OECD 111 guide is not applicable for the test item.

Key study: Tier 3 study with Wasox-VMAC2: An hydrolysis assessment of Wasox VMAC2 was performed according to Tier 3 of the OECD 111 guideline. The hydrolysis behaviour of the test item was examined at pH values normally found in the environment (pH 4 to 9) and under more acidic conditions (pH 1) for physiological purposes. Results of the preliminary tests clearly indicated very fast hydrolysis, fast liberation of the acetone oxime and methanol as well as immediate condensation to form highly cross-linked high molecular weight polymers. The identification of the test item as well as of the proposed main degradation products acetoxime and methanol was accomplished by means of 1H NMR spectroscopy. During the main assay it was confirmed that at all pH values acetoxime and methanol are the only soluble hydrolysis products. Also, it was observed that a gel was formed at each pH values. After 1H-NMR analysis, it was confirmed that this precipitate contains vinyl moieties in various chemical environment.

Key study: Hydrolysis of main components of Wasox-VMAC2: The test material is composed of several compounds, including the 3 main components acetone O,O'-[methoxy(vinyl)silanediyl]oxime; acetone O,O',O''-(vinylsilanetriyl)oxime and acetone O-[dimethoxy(vinyl)silyl]oxime. They polymerise, triggered by hydrolysis. The rate constants of hydrolysis and half-life times of the 3 main components were determined at pH 4, pH 7 and pH 9. Due to the predicted instability of the test substance, the test was performed at 25 °C and not at 50 °C as described in the guideline for the "preliminary test".

For the main component of the reaction mass, no "main test" was performed as the half-life time was < 1 h. The analysed concentration of acetoneO,O'-[methoxy(vinyl)silanediyl]oxime by gas chromatography, was below the limit of quantification (1.04 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

AcetoneO,O'-[methoxy(vinyl)silanediyl]oxime, the main component of the test substance(range: 45-70% w/w) is easily hydrolysable at each of the pH's tested.

For acetoneO-[dimethoxy(vinyl)silyl]oxime, component of the reaction mass, no "main test" was performed as the half-life time was < 1 h.The analyzed concentration by gas chromatography, was below the limit of quantification (0.16 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.

AcetoneO-[dimethoxy(vinyl)silyl]oxime, one of the main component of the test materials easily hydrolysable at each of the pH's tested.

For the acetoneO,O',O''-(vinylsilanetriyl)oxime, a component of the test substance, no "main test" was performed as the half-life time was < 1 h. The analysed concentration by gas chromatography, was below the limit of quantification (0.94 mg/mL) at 0.75 h after starting the dissolution of the test substance. More than 50 % of this component at pH 4, pH 7 and pH 9 hydrolysed in less than 1 hour at 25 °C.