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Endpoint:
hydrolysis
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Please refer to the attached QM(P)RF documents
Principles of method if other than guideline:
The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

The model for hydrolysis at pH 7 has been developed for, and applies specifically to linear and cyclic siloxanes. It is a multiple linear regression based model with descriptors representing (i) ring strain, (ii) number of Si-O bond, and (iii) number of Si-H bond.

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and apply specifically to organosilicon compounds. They are linear regression based models where the descriptor is the half-life at pH 7.
pH:
4
DT50:
0.1 h
Remarks on result:
other: 20-25°C
Remarks:
(Hydrolysis of H2-L2 to form intermediate hydrolysis product, dimethylsilanol)
pH:
5
DT50:
0.2 h
Remarks on result:
other: 20-25°C
Remarks:
(Hydrolysis of H2-L2 to form intermediate hydrolysis product, dimethylsilanol)
pH:
7
DT50:
1 h
Remarks on result:
other: 20-25°C
Remarks:
(Hydrolysis of H2-L2 to form intermediate hydrolysis product, dimethylsilanol)
pH:
9
DT50:
0.02 h
Remarks on result:
other: 20-25°C
Remarks:
(Hydrolysis of H2-L2 to form intermediate hydrolysis product, dimethylsilanol)
Conclusions:
Hydrolysis half-life values at 20-25°C of 0.1 h at pH 4, 1 h at pH 7 and 0.02 h at pH 9 were obtained using an accepted calculation method. The result is considered to be reliable.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-04-26 to 2011-06-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted using a modified OECD 111 test guideline. The modification is the use of higher loading rate of the co-solvent.
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
Use of higher (10%) col-solvent, one test temperature and pH was used and changes in parent concentration was only monitored.
Principles of method if other than guideline:
The extent of hydrolysis was determined by measuring disappearance of each parent compound in solution as a function of time by a solvent extraction method, followed by analytical determination using gas chromatography with selected ion monitoring mass spectrometry detection (GC-SIM-MS).
GLP compliance:
yes
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
Duplicate or triplicate samplings were conducted at each hydrolysis aging point. Temperatures were recorded once per day of sampling.
Buffers:
- pH: 7
- Type and final molarity of buffer: 0.005 M
- Composition of buffer: Imidazole and dilute hydrochloric acid
Details on test conditions:
TEST SYSTEM

- Sterilisation method: Nalgene sterile filtration unit with a 0.2 µm cellulose nitrate (CN) membrane.

- Measures to exclude oxygen: the buffer solution was sparged with an inert gas for a minimum of 5 mins. to exclude oxygen and carbon dioxide

- If no traps were used, is the test system closed

- Is there any indication of the test material adsorbing to the walls of the test apparatus? no

TEST MEDIUM
- Kind and purity of water: deionised water
Number of replicates:
Test substance: duplicate samples
Reference substance (hexamethyldisiloxane): triplicate samples
Positive controls:
not specified
Negative controls:
not specified
Statistical methods:
Linear regression analysis, average, standard deviation and relative standard deviation were calculated using Microsoft Office Excel 2007 12.0.6565.5003 SP2 MSO (12.0.6562.5003). Regression analyses of the hydrolysis data was conducted by 1. linear regression of natural log transformed data 2. non-linear regression analysis of raw data using Berkeley Madonna version 8.3.18, 1996-2010.
Preliminary study:
Preliminary study was not conducted.
Transformation products:
yes
No.:
#1
No.:
#2
Details on hydrolysis and appearance of transformation product(s):
Proposed hydrolysis mechanism: The proposed mechanism of hydrolysis of the test substance is (water omitted);
H(Me)2SiOSi(Me)2H - 2H(Me)2SiOH - 2HO(Me)2SiOH + H2
% Recovery:
ca. 90
pH:
7
Temp.:
25 °C
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0.062 min-1
DT50:
11.3 min
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Hydrolysis of H2-L2 to form intermediate hydrolysis product, dimethylsilanol
pH:
7
Temp.:
25 °C
DT50:
2.5 d
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Half-life for the hydrolysis of intermediate to form dimethylsilanediol
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0.06 d-1
DT50:
11.5 d
Remarks on result:
other: Repeat reference substance (hexamethyldisiloxane; half-life under standard conditions 5 d)

General description of GC-MS data:

No hydrolysis products were observed in the chromatograms for either substance since the GC-MS was configured to monitor ions specific to parent from of the test and reference substance.

Regression analysis of hydrolysis kinetic data:

The peak areas of test or reference substances in samples from the hydrolysis experiments were determined from the GC-MS data of the pentane extracts. The percent of parent substance remaining was calculated by comparison to peak areas of test or reference substance from direct spike results (normalized to the internal standard peak areas). Table 1 contains values of the hydrolysis rate constants, K and half-lives as well as the data range and number of time points included in the regression of each experiment.

Table 1: Summary of kinetic results based on regression analysis

 

pH buffer

pH with 10% ACN

Kinetic range

No of points

Slope K1b

SE K1

r2

Half-lifec

Parameter, Kfand Kr

Test substance (4-29-11)

7.000

6.958

13 – 93%

14

0.06159 min-1

 

0.0013 min-1

0.996

11.3 min

 

Reference substance (original)

(5-2-11)

7.000

6.958

28 – 77%

7

0.094 days-1

 

0.012 day-1

0.779

7.4 days

Kf= 0.364 day-1

Kr= 0.0030 µM-1day-1

NA

NA

1.9 days

Reference substance (repeat)

(5-27-11)

6.995

6.955

25 – 80%

9

0.060 days-1

 

0.010 day-1

0.596

11.5 days

Kf= 0.237 day-1

Kr= 0.00150 µM-1day-1

NA

NA

2.9 days

a Represent average % remaining for triplicate samplings at each point

b Values in italics are shown for information only

NA = not available

c Calculation: ln(2)/kior kf

Test substance:

Examination of the test substance plot shows expected first-order behavious spanning 2.9 half-lives. The kinetic range for data points varied from 46 seconds to 33 minutes. The experimental half-life was 11.3 min at pH 7 and nominal 25°C.

Reference substance:

Examination of the reference substance plot does not show the expected irreversible first-order behaviour. The value of Kf for the two experiments correspond to hydrolysis half-lives of 1.9 and 2.9 days respectively with an average of 2.4 days.

Time zero recoveries:

Table 2 present the time zero receoveries for both modified time zero samples and those treated the same way as the samples after spiking. There was no significant benefit to modifying the procedure for the time zero samples for the test or reference substance since average recovery for non-modified time zero samples were within the acceptable range of 90 - 110.

Table 2: Summary of time zero recoveries

 

Test substance

Reference substance (original)

Reference substance (repeat)

Time zero

% parent remaining

93.4 (49 sec)

86.8 (46 sec)

 

101.0 (61 sec)

102.4 (61 sec)

100.0 (54 sec)

101.7 (46 sec)

107.0 (48 sec)

Modified time zero

% parent remaining

90.3

89.5

107.3

100.2

 

Headspace analysis:

Table 3 contains the measured hydrogen concentration from headspace analysis of buffer solution spiked with the test substance, the amount of hydrogen formed over time with respect to the theoretical yield and natural log of transformation of hydrogen formed from the proposed intermediate product dimethylsilanol. Headspace analysis for hydrogen was performed to find out if the stoichiometric equivalent of hydrogen gas was formed on the same time scale as disappearance of test substance. If this were the case, it would suggest provide evidence that the disappearance of the parent molecule, as observed by solvent extraction/GC-MS, was due, at least in part to hydrolysis of the Si-H group on the test substance. Alternatively, a slow rate of H2 formation would suggest the breaking of the siloxane bond was the prevalent process initially.

The headspace analysis of hydrolysis samples demonstrated that very little hydrogen gas was formed on the timescale of disappearance of the test substance by the solvent extraction/GC-MS method.

 Table 3: Summary of headspace analysis of hydrogen from test substance

Sample reference

Age of sample, days

H2concentration from calibration curve, moles/L

% H2formeda

Natural log intermediate hydrolysis product remainingb

1

0.042

2.0E-05

1.03%

1.1E-02

2

0.786

3.2E-04

17.79%

2.0E-01

3

1.004

3.7E-04

20.50%

2.3E-01

4

1.983

7.4E-04

41.41%

5.3E-01

5

3.078

1.2E-03

66.10%

1.1E+00

6

4.788

1.3E-03

70.45%

1.2E+00

a Based on 100% quantitative conversion of test substance to hydrogen gas or 1.8x10-3moles/H2

b Based on kinetic equation -1x ln (1 – [H2]/[(Me)2HSiOH]o

The apparent half-life of the intermediate hydrolysis product was 2.5 days. Therefore, the result support that the mechanism of degradation of the test substance in water began with the hydrolysis of the siloxane bond. The rapidly formed intermediately was subsequently degraded by slower hydrolysis of the SiH group to yield hydrogen gas and DMSD, although the later was not observed directly. The relative rates of these reactions could vary with pH and temperature.

Total silicon by ICP analysis:

Table 4 shows the concentration of substance in each sample, expected Si concentration, measured Si concentration and the percent of expected Si (receoveries). The ICP recoveries of total Si for test substance were 100% and 104% for the duplicate aged samples (aged 18 days), which were in good agreement with recoveries of the neat DMSD QC samples.

Table 4: Total silicon by ICP

 

Age of sample (day)

Substance conc µg/g

Expected Si µg/g

Measured Si µg/g

% of expected Si

Calibration curve

Blank 1

18

0

0

<DL

 

Slope = 22511

Y int. = -5053.6

R2= 0.9999

Blank 2

18

0

0

<DL

 

Acidified Blank 1

4b

0

0

<DL

 

Acidified Blank 2

4b

0

0

<DL

 

Test-subst 1

18

12.69

5.307

100a

 

Test-subst 2

18

12.76

5.337

104a

 

Ref subst 1

15

12.20

4.220

10.66

253

Ref subst 2

15

12.15

4.201

10.43

248

Acidified ref subst 1

15b

12.27

4.245

48.80

443

Acidified ref subst 2

15b

12.19

4.218

19.16

454

ClSi(Me)2H-1

4

12.77

3.790

9.76

258a

ClSi(Me)2H-2

4

12.78

3.793

9.25

244a

HOSi(Me)3-1

1

11.78

3.669

16.20

442

HOSi(Me)3-2

1

11.76

3.662

17.20

465

(HO)2Si(Me)2-1

1

11.62

3.542

3.86

109

(HO)2Si(Me)2-2

1

11.52

3.511

3.28

93

a Triplicate measurements during method development gave essentially the same results with an average % of expected Si of 139% and 141% for aged test substance and aged chlorodimethylsilane (both aged 7 days) respectively

b Acidified 5-13-11 and analysed by ICP 5-17-11

DL = Detection

Validity criteria fulfilled:
yes
Conclusions:
A hydrolysis half-life of 11.3 minutes at pH 7 and 25°C was determined for the formation of intermediate hydrolysis product, dimethylsilanol using a modified OECD 111 test method. The result is considered reliable.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Not a Guideline hydrolysis study, not under GLP. Study conducted according to generally acepted scientific criteria to establish comparative hydrolysis rates at pH7.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Objective: to measure the hydrolysis rates of tetramethylcyclotetrasiloxane (1H-D4) relative to octamethylcyclotetrasiloxane (D4) in pH 7 imidazole buffer containing 20% acetonitrile co-solvent at nominal 25 °C. The extent of hydrolysis was determined by measuring disappearance of each parent compound in solution as a function of time by a solvent extraction method, followed by analytical determination using gas chromatography with flame ionization detection (GC-FID). IPC analysis of the hydrolysis samples was used to determineconservation of silicon, as evidence that the disappearance of the parent compound was due to hydrolysis over other potential loss mechanisms, e.g. volatisation. Headspace analysis for hydrogen gas was used obtain information on the mechanism of hydrolysis.
GLP compliance:
no
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products: 7 times / 10 minutes
- Sampling methods for the volatile compounds, if any: aging tubes were fillled to the top to minimize headspace. at the appropriate timepoint, around 4 ml was extracted to create space for the extraction fluid (hexane). After injection of 1 ml of hexane, tube Mininert valvase were replaced by a solidcap with teflon liner, the sample was vortexed for 2 minutes and , centrifuged
- Sampling intervals/times for pH measurements: not given.
- Sampling intervals/times for sterility check: n.a
- Sample storage conditions before analysis: n.a.
- Other observation, if any (e.g.: precipitation, color change etc.): n.a.
Buffers:
- pH: 7.0
- Composition of buffer: Starting from Millipore Millli-Q Integral 5deionized water, 0.005 M aqueous buffer made by titration of imidazole with dilute hydrochloric acid solution to pH 7.2. After addition of the co-solvent ACN, the pH was 7.0
- The buffer solution was sparged with an inert gas for a minimum of 5 min to exclude oxygen and carbon dioxide, and was sterilized using a Nalgene sterile filtration unit with a 0.20 micrometre cellulose nitrate (CN) membrane.
Details on test conditions:
Remarks Field for Test Conditions
1 Duration (days): ~0.1 (test substance) to 49 (positive control)
2 Positive controls: Octamethylcyclotetrasiloxane (CAS No. 556-67-2)
3 Negative controls: None.
4 Analytical procedures:
4.1 Dissipation of test substance – Decreases in concentration of the test substance or positive control substance from the aqueous-organic buffer solution over time were determined using a solvent extraction method, followed by gas chromatography with flame ionization detection (GC-FID) for measurement of analyte in the extract. The method was calibrated with solvent standards of the test substance or positive control containing an internal standard, n-nonane. Analysis of fortified extraction solvent was used to verify performance of the GC-FID method.
4.2 Formation of hydrogen gas – The formation of hydrogen gas formed by hydrolysis of SiH moieties associated with the test substance was determined by a headspace gas chromatography method with thermal conductivity detection. The method was calibrated with standards prepared by addition of known volumes of pure H2 gas to sealed headspace vials.
4.3 Mass balance determination – Inductively coupled plasma emission spectroscopy (ICP) was used to directly analyze some reaction solutions for total silicon content after the parent test substance could no longer be detected. This permitted demonstration of mass balance, despite the lack of specific data on the hydrolysis products. The ICP method was calibrated using matrix-matched standards prepared from dimethylsilanediol in the same aqueous-organic buffer used for the hydrolysis reactions. Independent check standards were used to verify performance of the method.
5 Study Design:
5.1 Reactions were carried out in aqueous-organic imidazole-HCl buffer containing 20% v/v acetonitrile to enhance solubility and minimize potential for loss of test substance by volatilization or sorption.
5.2 A positive control, octamethylcyclotetrasiloxane, having well-established hydrolysis half-lives in 100% aqueous buffers (Durham and Kozerski, 2005) was used to evaluate effect of organic solvent on hydrolysis kinetics.
5.3 Only pH 7 was studied, as this condition gave the longest half-life, 3-4 days, for hydrolysis of the positive control in 100% aqueous buffer.
Duration:
68 h
pH:
7
Temp.:
25
Number of replicates:
all samples in duplicate
Positive controls:
yes
Remarks:
Octamethylcyclotetrasiloxane (D4)
Negative controls:
no
Preliminary study:
not performed
Test performance:
all tests done in duplicate
Transformation products:
not measured
% Recovery:
ca. 74.9
pH:
7
Temp.:
22.5 °C
Duration:
ca. 0.78 min
% Recovery:
ca. 77.1
pH:
7
Temp.:
22.5 °C
Duration:
ca. 0.75 min
% Recovery:
ca. 45.6
pH:
7
Temp.:
22.5 °C
Duration:
ca. 2.25 min
% Recovery:
ca. 50
pH:
7
Temp.:
22.5 °C
Duration:
ca. 2.07 min
% Recovery:
ca. 24.7
pH:
7
Temp.:
22.5 °C
Duration:
ca. 4.08 min
% Recovery:
ca. 11.5
pH:
7
Temp.:
22.5 °C
Duration:
ca. 6.37 min
% Recovery:
ca. 7.2
pH:
7
Temp.:
22.5 °C
Duration:
ca. 7.78 min
% Recovery:
ca. 1.9
pH:
7
Temp.:
22.5 °C
Duration:
ca. 12.25 min
% Recovery:
ca. 2
pH:
7
Temp.:
22.5 °C
Duration:
ca. 12.05 min
% Recovery:
ca. 0
pH:
7
Temp.:
22.5 °C
Duration:
ca. 103.75 min
pH:
7
Temp.:
22.5 °C
DT50:
2.2 min
Type:
not specified

Table 1. summary of kinetic results based on linear regression analysis



Date

Initiated

pH

Kinetic Range

Number of Points

Slope,

k1

SE,

k1

r2

t1/2

1H-D4

4-30-10

7.003

2-77%

14

0.3156 min-1

0.0045 min-1

0.9976

2.2 min

D4

4-13-10

6.933

40-89%

16

0.01558 days-1

0.0014 days-1

0.8941

44 days



Table 2: recovery of Tetramethylcyclotetrasiloxane (30 April 2010)


Sample

Reference

Age

min

%

Remaining

ln

0A

0.78

74.9

1.7187

0B

0.75

77.1

1.7689

2A

2.25

45.6

1.0471

2B

2.07

50.0

1.1473

4A

4.08

24.7

0.5666

4B

4.02

22.5

0.5159

6A

6.08

12.8

0.2940

6B

6.37

11.5

0.2646

8A

8.05

7.2

0.1656

8B

7.87

7.2

0.1659

10A

10.12

3.9

0.0896

10B

10.12

4.2

0.0962

12A

12.25

1.9

0.0445

12B

12.05

2.0

0.0465

60A

103.75

Not detected


60B

60.05

Not detected



Table 3: summary of headspace analysis for hydrogen from 1H-d4

Sample Reference

Age of Sample, hrs

H2Concentration from Calibration Curve, moles/L

% H2Formeda

A

0.20

2.35×10-6

0.52

B

0.33

4.44×10-6

0.99

C

0.67

1.42×10-5

3.17

D

1.85

5.27×10-5

11.73

E

20.50

3.52×10-4

78.40

F

27.13

4.17×10-4

92.89

G

43.47

3.49×10-4

77.79

H

67.95

2.80×10-4

62.34


aBased on 100% quantitative conversion of 1H-D4 to Hydrogen gas or 4.56×10-4moles/L H2


Table 4: total silicon by icp



Test Substance Concentration

µg/g

Expected Si

µg/g

Measure Si

µg/g

% of Expected Si

(% Recovery)

Calibration Curve

1H-D4 1

2.81

1.31

1.97

150

Slope = 12835

1H-D4 2

2.80

1.30

1.78

137

Y intercept = +213.02

D4 1

2.76

1.04

2.55

245


D4 2

2.76

1.04

2.52

242


Methyltrimethoxysilane 1

2.98

0.61

1.10

180

Slope = 4707

Methyltrimethoxysilane 2

2.98

0.61

1.23

201

Y intercept =

Dimethylsilanediol 1

2.79

0.85

1.25

147

-544.71

Dimethylsilanediol 2

2.90

0.88

1.34

152

R2= 0.9998

Methyldimethoxysilane 1

2.88

0.76

1.57

207


Methyldimethoxysilane 2

2.86

0.75

1.60

212


Silicate standard 1

1.21

1.21

1.34

111


Silicate standard 2

1.98

1.98

2.67

135



Conclusions:
The submitted substance rapidly disappears from a buffered aqueous solution at pH7, with a half-life of 2.2. minutes.
ICP analysis to determine conservation of Si demonstrates that disappearance of test substance was degradation, not volatilization.
Hydrolytic degradation of the test substance is rapid even under pH 7 conditions, associated with the greatest stability of the positive control in an OECD 111 guideline study.
Under modified test conditions (i.e. aqueous-organic buffer containing 20% acetonitrile), the hydrolysis half-life of the positive control substance was substantially longer than under the reference condition (i.e., 100% aqueous), suggesting that the experimental results for the test substance are conservative.
Quantitative evolution of hydrogen gas from hydrolysis of the Si-H bonds of the test substance further supports that mass balance was conserved under the test conditions, but was relatively slow compared to disappearance of the parent compound; this indicated that ring-opening hydrolysis of the cyclic siloxane was the initial mechanism of degradation.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Please refer to the attached QM(P)RF documents
Principles of method if other than guideline:
The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details). The model for hydrolysis at pH 7 has been developed for, and applies specifically to, siloxanes. It is a multiple linear regression based model with descriptors representing (i) ring strain, (ii) number of Si-O bonds, and (iii) number of Si-H bonds.

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and apply specifically to, organosilicon compounds. They are linear regression based model where the descriptor is the half-life at pH 7.
pH:
4
DT50:
0.01 h
Remarks on result:
other: 20-25°C
pH:
5
DT50:
0.03 h
Remarks on result:
other: 20-25°C
pH:
7
DT50:
0.02 h
Remarks on result:
other: 20-25°C
pH:
9
DT50:
<= 0.08 min
Remarks on result:
other: 20-25°C
Conclusions:
Hydrolysis half-life values at 25°C of 0.01 h at pH 4, 0.03 h at pH 5, 0.02 h at pH 7 and ≤5 seconds at pH 9 were obtained using a validated QSAR method. The result is considered to be reliable.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
GLP compliance:
yes
Specific details on test material used for the study:
Not applicable
Radiolabelling:
yes
Analytical monitoring:
yes
Details on sampling:
Sample tubes were removed from storage at the predetermined time and opened. The entire volume (ca. 2.2 mL) was transferred to a 2.5 mL gastight syringe. From the syringe, ca. 1 g was weighed into a vial containing scintillation cocktail and analysed by LSC to evaluate 14-C solution recovery. The remaining solution was used to overfill the 1 mL sample loop on the manual injection valve on the radio-HPLC system, followed by injection. The emptied tube was rinsed twice with THF and the rinses combined in a separate cocktail-filled scintillation vial for LSC analysis.
Sampling intervals were determined according to the expected half-life in each experiment; 12 samples were used per experiment.
Buffers:
  To minimize the potential for buffer catalysis, the test system consisted of 0.005 M aqueous buffers made by titration of acetic acid and boric acid with lithium hydroxide for pH 5 and 9, respectively, and imidazole with hydrochloric acid for pH 7.
Details on test conditions:
Reactions were conducted in flame sealed borosilicate glass tubes to reduce volatilization and surface sorption.
Hydrolysis experiments were carried out at 10, 25 and 35°C and pH 5, 7 and 9.
Preparation of the test substance solution: A primary stock solution was prepared by diluting the 14C-HMDS test substance in THF. A portion of this solution was diluted in THF to create a final test substance solution for spiking into the test system. The concentration of the final solution was chosen to target and initial test substance concentration upon spiking of 0.2 ppm (which is ca. 25% of the aqueous solubility of HMDS). The spiking solution was prepared so that the amount of THF solvent in the test system was <1%. The solution was stored in a freezer when not in use to minimise evaporation.
Conduct of the hydrolysis experiments: Kinetic experiments were initiated by weighing 50 g of aqueous buffer into the open barrel of a 100 mL glass gastight syringe and spiking volumetrically using a gastight syringe with 500 µL of the 14C-HMDS test substance solution. After the plunger was replaced, the headspace was purged from the syringe and the solution was transferred to a series of numbered glass reaction tubes. Tubes were filled in order but selected randomly for analysis. The samples were incubated at the appropriate temperature. At a predetermined time, the sample tube was removed from storage.
During the tube filling process ca. 1g aliquotes of the solution in a large volume syringe were weighed directly into a series of 3 scintillation vials (before filling the first tube, after filling approximately half the tubes and after filling the last tube). These were analysed by LSC to determine the spiked initial concentration against which recovery was assessed.
Sample age was determined as the difference between spike time and injection on the HPLC system.
At pH 5, 35°C, the rapid rate of hydrolysis meant the sampling interval was less than the HPLC cycle time. Therefore, sample tubes were removed from the incubator and placed in ice. The time of this transfer was used to determine the sample age. Samples were withdrawn sequentially for analysis within 5 hours.
Duration:
1 250 h
pH:
7
Temp.:
10 °C
Duration:
700 h
pH:
7
Temp.:
25 °C
Duration:
156
pH:
7
Temp.:
35 °C
Duration:
35 h
pH:
5
Temp.:
10 °C
Duration:
5.5 h
pH:
5
Temp.:
25 °C
Duration:
4 h
pH:
5
Temp.:
35 °C
Duration:
192 h
pH:
9
Temp.:
10 °C
Duration:
32 h
pH:
9
Temp.:
25 °C
Duration:
11 h
pH:
9
Temp.:
35 °C
Number of replicates:
One at each pH and temperature, except for pH 5, 25°C where two replicates were used.
Statistical methods:
The hydrolysis of HMDS in dilute aqueous solution was observed to follow pseudo first-order kinetics. The natural logarithm of the concentration was plotted as a function of time. The observed rate constant, k, for the hydrolysis reaction is equal to the slope of a first-order regression line fitted to the data. The half-life of the hydrolysis reaction was calculated from the estimated rate constant according to the following equation: t1/2 = ln 2/k, where k is the reaction rate constant and t1/2 is teh half-life of the test substance.

The observed rate constants as a function of temperature at the two extremes of pH were used to construct an Arrhenius diagram for each catalytic condition by plotting ln k against 1/T for constant pH (5 or 9), where T is the temperature in K. According to the logarithmic form of the Arrhenius equation, ln k = -(Ea/RT) + ln A, the activation energy, Ea, is readily obtained from the slope of the aforementioned plot. Using the values of the Arrhenius parameters, the rate constant can be calculated at any temperature. Descriptive statistics such as average, standard deviation, relative standard deviation (RSD) and linear regression analysis were also performed.
Preliminary study:
The preliminary study at 50°C was not conducted as HMDS was expected to have a hydrolysis half life of less than 1 year.
Test performance:
The challenges of designing an experiment to study the hydrolysis kinetics of HMDS include its low water solubility (0.9 ppm), high vapour pressure (52 mm Hg at 30°C) and Henry's law constant ranging from 1.3 to 2.4. To eliminate auxiliary losses of HMDS from the system and to unequivocally demonstrate hydrolytic degradation, the present methodology is based on use of one-piece, hermetically sealled glass reaction vessels. Equally important is the use of 14-C labelled HMDS to facilitate tracking of recoveries and speciation of parent test substance and final product using established radiochemical analytical techniques.
Average recoveries ranged from 75 to 04% with an average of 87% for all experiments. 10% better recoveries were observed for pH 5 and 9 relative to neutral pH. Only minor variation in recovery across temperature was observed.
Of greater importance is consideration of how recovery profiles varied through the series of samples within a given experiment. In most cases the difference between minimum and maximum recovery was <15%. The authors of the study conclude that most losses occurred during sampling and this was dealt with by normalising each sample to the total 14-C activity in the respective radiochromatogram.
Transformation products:
yes
No.:
#1
Details on hydrolysis and appearance of transformation product(s):
- Formation and decline of each transformation product during test: The formation of the transformation product trimethylsilanol was followed udring the test.
% Recovery:
75 - 94
pH:
5
Temp.:
9.8 °C
Hydrolysis rate constant:
0.156 h-1
DT50:
4.45 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 24-82%; Number of points: 8; SE rate constant: 0.00180 r2 0.9992
pH:
4.99
Temp.:
24.8 °C
Hydrolysis rate constant:
0.471 h-1
DT50:
1.47 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 13-86%; Number of points: 10; SE rate constant: 0.00436 r2 0.9993
pH:
5
Temp.:
24.8 °C
Hydrolysis rate constant:
0.492 h-1
DT50:
1.41 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 11-93%; Number of points: 9; SE rate constant: 0.00519 r2 0.9992
pH:
5.02
Temp.:
33.7 °C
Hydrolysis rate constant:
0.84 h-1
DT50:
0.83 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 11-88%; Number of points: 9; SE rate constant: 0.0113 r2 0.9987
pH:
7.01
Temp.:
9.8 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
418 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 13-93%; Number of points: 10; SE rate constant: 0.0000146 r2 0.9994
pH:
7.01
Temp.:
24.7 °C
Hydrolysis rate constant:
0.006 h-1
DT50:
116 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 12-85%; Number of points: 8; SE rate constant: 0.000143 r2 0.9966
pH:
7.01
Temp.:
33.8 °C
Hydrolysis rate constant:
0.013 h-1
DT50:
53.4 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 13-93%; Number of points: 9; SE rate constant: 0.000293 r2 0.9964
pH:
9.02
Temp.:
9.8 °C
Hydrolysis rate constant:
0.008 h-1
DT50:
86 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 22-99%; Number of points: 10; SE rate constant: 0.000125 r2 0.9981
pH:
9.01
Temp.:
24.8 °C
Hydrolysis rate constant:
0.056 h-1
DT50:
12.4 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 16-99%; Number of points: 11; SE rate constant: 0.000514 r2 0.9992
pH:
8.99
Temp.:
33.9 °C
Hydrolysis rate constant:
0.171 h-1
DT50:
4.07 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: Kinetic range: 27-99%; Number of points: 8; SE rate constant: 0.00672 r2 0.9908
Other kinetic parameters:
Estimated catalytic constants for the hydrolysis of HMDS:
k(H3O+ / M-1 h-1): 15600 at 10°C, 47600 at 25°C, 84000 at 35°C
k(OH- / M-1 h-1): 766 at 10°C, 5480 at 25°C and 17400 at 35°C
Details on results:
Total recovery derived from following degradation at pH 7 and 12 °C: Degradation (in %): 50 after 15 day(s)

Degradation products (CAS No./EC No./EINECS Name): 1066-40-6   213-914-1 hydroxytrimethylsilane

t1/2 pH5:  = 4.5 hours at 9.8 oC = 1.4 hours at 24.8°C  = 0.8 hours at 33.7°C

t1/2 pH7: = 418 hours at 9.8 oC = 116 hours at 24.7°C  = 53 hours at 33.8°C

t1/2 pH9: = 86 hours at 9.8 oC = 12 hours at 24.8°C = 4.1 hours at 33.9°C

Degradation pH 8.0 at 9°C (a condition that is relevant for marine water)  = 50% after 34 days Degradation product: Trimethylsilanol (CAS No. 1066-40-6) The hydrolysis of hexamethyldisiloxane was observed to follow first-order kinetics, was pH dependent in the range 5 to 9, and showed strong temperature dependence for pH >= 7.  The catalytic constants for the hydronium and hydroxide ion catalyzed hydrolysis reactions were estimated from the observed rate constants in the 10-35  C range at pH 5 and 9.  The ranges of values for the catalytic constants, kH3O+ = 1.56×104-8.40×104  M 1 h-1 and kOH  = 766-1.74×104 M 1 h-1, demonstrated that acid catalysis was more efficient than base catalysis over the entire temperature range.  Predicted rates of hydrolysis for pH 7 based on these catalytic constants agreed with measured values to within 15% for 10 and 25 oC; within 23% for 35 oC.  Average solution recovery of 14C activity was above 90% for reactions conducted at pH 5, and above 80% for reactions conducted at pH 9.  For pH 7 the average recovery was slightly above 80% for 10 and 25 oC and 75% for 35 oC.  The recoveries showed no significant dependence on temperature, nor did the recoveries typically vary in a significant and systematic manner within a single experiment.

Solvent rinses contributed minimally to the total recovery, suggesting little or no physcial adsorption of the test substance or hydrolysis products.

Average 14C Recoveries within each experiment

pH

Temp / °C

Fitted Data Points - Average Solution Recovery

Fitted Data Points - High Recovery

Fitted Data Points - Low Recovery

All Data Points - Average Solution Recovery

All Data Points - High Recovery

All Data Points - Low Recovery

5.00

9.8

91.7

97.1

85.1

91.7

97.1

85.1

4.99

24.8

93.5

98.2

87.7

93.9

98.2

87.7

5.00

24.8

91.2

94.2

87.1

91.2

94.2

87.1

5.02

33.7

93.4

97.7

89.2

94.4

99.7

89.2

7.01

9.8

79.9

83.0

77.6

80.6

88.0

77.6

7.01

24.7

82.1

85.4

79.2

81.3

86.4

71.1

7.01

33.8

73.9

81.4

64.1

75.3

88.2

64.1

9.02

9.8

84.5

88.2

81.1

84.5

88.2

81.1

9.01

24.7

89.4

93.7

82.5

89.4

93.7

82.5

8.99

33.9

84.6

88.0

80.0

85.3

90.3

80.0

Validity criteria fulfilled:
yes
Conclusions:
Hydrolysis half lives of 1.5, 116 and 12 h at pH 5, 7 and 9, respectively, were determined at 25°C in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Principles of method if other than guideline:
The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

The model for hydrolysis at pH 7 has been developed for, and applies specifically to linear and cyclic siloxanes. It is a multiple linear regression based model with descriptors representing (i) ring strain, (ii) number of Si-O bond, and (iii) number of Si-H bond.

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and apply specifically to organosilicon compounds. They are linear regression based models where the descriptor is the half-life at pH 7.
pH:
4
DT50:
1.5 h
Remarks on result:
other: 20-25°C
Conclusions:
Hydrolysis half-life values at 20-25°C of 1.5 h at pH 4 was obtained using an accepted calculation method. The result is considered to be reliable.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Principles of method if other than guideline:
Studies were conducted at 1.5±0.5 °C to slow the hydrolysis reaction rate.
GLP compliance:
no
Analytical monitoring:
no
Details on sampling:
Not applicable
Buffers:
Buffers were selected because they had a very low or non-detectable chloride ion concentration. Buffers were prepared by titration of acetic acid, sodium phosphate monobasic or boric acid with sodium hydroxide. Constant ionic strength of 0.50 M was maintained by addition of appropriate volumes of 5 M sodium nitrate solution. Buffer solutions were made to known final volumes in polypropylene volumetric flasks with deionized water. Final pH adjustments were made by dropwise addition of a 2M sodium hydroxide solution using a calibrate pH meter. Prior to use, all buffer solutions were sparged with argon for at least 15 minutes to exclude oxygen and carbon dioxide. The buffers were not sterilized. The pH of each buffer solution was measured just prior to the kinetic experiment for which it was used.

- pH: Target: 4.0; Measured: 4.00
- Type and final molarity of buffer: Acetic Acid/Sodium Hydroxide, 0.20M
- Composition of buffer: 100mL 1.00 M Acetic Acid solution, 20 mL 1M Sodium Hydroxide solution, 46 mL 5M Sodium Nitrate solution. Total volume 500 mL.

- pH: Target: 7.0; Measured: 7.01
- Type and final molarity of buffer: Sodium Phosphate, monobasic/Soidum Hydroxide, 0.20M
- Composition of buffer: 100mL 1.00 M Sodium Phosphate, monobasic solution, 61.5 mL 1M Sodium Hydroxide solution, 5.4 mL 5M Sodium Nitrate solution. Total volume 500 mL.

- pH: Target: 9.0; Measured: 8.99
- Type and final molarity of buffer: Boric acid/Sodium hydroxide, 0.30M
- Composition of buffer: 9.27 g boric acid (neat reagent), 53 mL 1M Sodium Hydroxide solution, 39.5 mL 5M Sodium Nitrate solution. Total volume 500 mL.
Estimation method (if used):
Not applicable.
Details on test conditions:


TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: The vessels used for the individual hydrolysis experiments were wide mouth low-density polyethylene bottles (Cole-Parmer/Bel-Art, 90 mL, 52 x 69 mm) with screw caps. Plastic, instead of glass containers were used since it is
known that the SiOH layer on glass will react with SiCl compounds (Smith, A.L., The Analytical Chemistry of Silicones (1991) 112, 29.). One screw cap was fitted with a rubber grommet to hold the chloride electrode securely in place and a rubber septa (Aldrich, Suba-Seal, i.d. 9.5 mm) to allow injection of the chlorosilane solution using a microliter syringe. The modified screw cap w as used with a new vessel for each pH and chlorosilane hydrolysis experiment after replacing the rubber septa and cleaning the chloride electrode with deionized water.
- Sterilisation method: The vessels were not sterilized.
- Lighting: No details given.
- Measures taken to avoid photolytic effects: No photolytic effects expected.
- Measures to exclude oxygen: Stock solutions of the test substance were prepared in a nitrogen-purged glove bag. Buffer solutions were purged with argon for 15 minutes before use.
- Details on test procedure for unstable compounds: The test substance is very unstable in contact with moisture. Acetonitrile was used to make up the stock solutions; it is considered a suitable solvent for chlorosilanes. Solutions of the test substance were prepared inside a nitrogen-purged glove bag and stored in 22-mL plastic vials having septum lined open-top caps (oven dried to remove trace moisture). When not in use, the kinetic solutions were stored in a secondary airtight container filled with Drierite.
- Details of traps for volatile, if any: None.
- If no traps were used, is the test system closed/open: Closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus?: No (see comments above on selection of test vessels)

TEST MEDIUM
- Volume used: 450 µL of the test substance in acetonitrile was injected into 50 mL of the buffer solution.
- Preparation of test medium: A 0.1M stock solution of the test substance in acetonitrile was prepared. This was injected directly into the buffer solution at the start of the hydrolysis experiment.
- Renewal of test solution: Not applicable.
- Identity and concentration of co-solvent: Acetonitrile (99.93% purity), 0.9% in final test solution.

OTHER TEST CONDITIONS
- Adjustment of pH: No pH adjustment was carried out during the test.
- Dissolved oxygen: No details given.
Duration:
2.3 min
pH:
4
Initial conc. measured:
0.001 mol/L
Duration:
4 min
pH:
7
Initial conc. measured:
0.001 mol/L
Duration:
2.7 min
pH:
9
Initial conc. measured:
0.001 mol/L
Number of replicates:
Replicates:  One at pH 4, 7, and 9
Positive controls:
not specified
Negative controls:
not specified
Statistical methods:
Since the hydrolysis was so rapid, there was insufficient data to use statistical methods to interpret the results.
Preliminary study:
The substance is known to be unstable at environmentally relevant temperatures, therefore, no preliminary study was required.
Test performance:
There were a few instances where higher than expected [Cl-] readings (called spikes hereafter) were observed. The definitive reason for the spikes is unknown, however, possible causes were: (a) hydrolysis product precipitate physcially striking the sensing membrane, or (b) the chlorosilane solution was injected into the buffer too fast causing a distrubance to the sensing membrane, or (c) the chloride ion concentration was temporarily concentrated near the sensing membrane prior to achieving a homogeneous solution. The spikes had no effect on the hydrolysis results.
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: Increase in chloride ion concentration was measured during the test.  For given solution conditions,the degradation product hydrogen chloride was observed to be stable during data collection.  Consequently, HCl was considered stable. The total concentrations of chloride ion as a percentage of the theoretical concentration at the end of the tests were 99%, 105% and 95% at pH 4, 7 and 9, respectively.
The stability of silanol was not measured, however silanols will undergo condensation reactions to form siloxanes (Smith, A. L., The Analytical Chemistry of Silicones 1991, 112, 12).
- Pathways for transformation: Due to the limitation imposed by the response time of the ion selective electrode, only the total hydrolysis could be studies potentiomaterically. It was not possible to differentiate between first, second and third chloride ion replacement by a hydroxyl group from the aqueous buffer, producing a silanol.
pH:
4
Temp.:
1.5 °C
DT50:
ca. 0.2 min
Type:
not specified
Remarks on result:
other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material (based on chloride ion concentration) assuming the first hydrolysis step is rate limiting.
pH:
7
Temp.:
1.5 °C
DT50:
ca. 0.3 min
Type:
not specified
Remarks on result:
other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material (based on chloride ion concentration) assuming the first hydrolysis step is rate limiting.
pH:
9
Temp.:
1.5 °C
DT50:
ca. 0.1 min
Type:
not specified
Remarks on result:
other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material (based on chloride ion concentration) assuming the first hydrolysis step is rate limiting.
Other kinetic parameters:
None determined.
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

MAJOR TRANSFORMATION PRODUCTS
The chloride ion concentration was measured over the course of the hydrolysis. Measured concentrations are given in Tables 1-3.

INDICATION OF UNSTABLE TRANSFORMATION PRODUCTS:
- The silanol hydrolysis product is known to undergo condensation to siloxanes, however, the test report does not indicate that this was observed during the hydrolysis test.

PATHWAYS OF HYDROLYSIS
- Description of pathways: Hydrolysis is thought to proceed via consecutive replacement of Si-Cl with Si-OH. Due to the rapidity of the hydrolysis
further study of reaction pathways was not possible.
- Figures of chemical structures attached: No

Since the hydrolysis was so rapid, there was insufficient data to determine rate constants for the hydrolysis reactions by regression modelling. First order or psuedo-first order behaviour could not be confirmed because: (a) sparse nature of the data during the critical portion of the process (20 -70%) hydrolyzed), b) the inherent limitation associated with measuring co-product concentration for consecutive reactions, and (c) the relationship between k1, k2 and k3 is not known. Although rate constants and half-lives could not be determined quantitatively, the data was adequate for estimating the upper limit of t1/2.

Tables 1 - 3 show the results of the chloride ion measurements during the hydrolysis experiments. Table 4 illustrates the calculation of the hydrolysis half-lifes at each pH.

Table 1. Results at pH 4

Time (sec)

[Cl-] (mM)   Blank Corrected [Cl-] (mM)*  % of Theoretical [Cl-]

10

0.699 0.667  33 

20

0.748  0.716 35

30

1.08  1.05 52

40

1.22  1.19 59

50

1.43  1.40 69

60

1.59  1.56 77

70

1.78  1.75 87
80 1.95  1.92 95
90 2.02  1.99 99
100 2.03  2.00 99
110 2.03  2.00  99
120 2.03 2.00  99
130 2.03  2.00  99 
140  2.03   2.00 99 

* Subtracted chloride ion concentration measured in buffer blank = 0.0325 mM.

Table 2. Results at pH 7

Time (sec)

[Cl-] (mM)   Blank Corrected [Cl-] (mM)*  % of Theoretical [Cl-]

10

0.134 0.107 5

20

0.665 0.638 32

30

0.844 0.817 41

40

1.04 1.01 50

50

1.21  1.18 59

60

1.34  1.31 65

70

1.44 1.41 70
80 1.54  1.51 75
90 1.63  1.60 79
100 1.73 1.70 84
110 1.82 1.79 89
120 1.87 1.84 91
130 1.92 1.89 94
140  1.97  1.94 96
 150  2.02  1.99  99
 160  2.07  2.04  101
 170  2.10  2.07  103
 180  2.12  2.09  104
 190  2.14  2.11  105
 200  2.14  2.11  105
 210  2.14  2.11  105
 220  2.14  2.11  105
 230  2.15  2.12  105
 240  2.15  2.12  105

* Subtracted chloride ion concentration measured in buffer blank = 0.0275 mM.

Table 3. Results at pH 9

Time (sec)

[Cl-] (mM)   Blank Corrected [Cl-] (mM)*  % of Theoretical [Cl-]

10

1.68 1.64 81

20

1.21 1.17 58

30

1.45 1.41 70

40

1.64 1.60 79

50

1.81 1.77 88

60

1.87  1.83 91

70

1.89  1.85 92
80 1.91  1.87 93
90 1.92  1.88 94
100 1.93 1.89 94
110 1.93 1.89 94
120 1.93 1.89 94
130 1.95 1.91 95
140  1.94  1.91 94
 150  1.95  1.91  95
 160  1.95  1.91  95

* Subtracted chloride ion concentration measured in buffer blank = 0.0405 mM.


Table 4. Overall results

pH

Time to total hydrolysis  % Theoretical [Cl-] at this temperature t1/2 / s*

4

100 99 10

7

170 102 17

9

70 92 7


* Time to total hydrolysis / 10


Validity criteria fulfilled:
yes
Conclusions:
A hydrolysis half-life of ca. 0.3 minutes at pH 7 for dimethyldichlorosilane was determined in a reliable study conducted according to an appropriate test protocol. It was not conducted according to GLP.
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
GLP compliance:
yes
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products: Immediately after addition of the test substance to the buffer and then at 1 minute intervals.
- Sampling method: Approximately 800µL of test solution was quickly transferred to an NMR tube using a clean dried 1000µL syringe.
Buffers:
- pH: Target: 4.0; Measured: 4.02
- Type and final molarity of buffer: Formic Acid/Sodium Hydroxide, 0.05M
- Composition of buffer: 0.237 g Acetic Acid, 1.24 mL 2M Sodium Hydroxide solution, 1.323 g NaCl. Total volume 100 mL.

- pH: Target: 7.0; Measured: 7.00
- Type and final molarity of buffer: Sodium Phosphate, monobasic/Soidum Hydroxide, 0.05M
- Composition of buffer: 0.600 g Sodium Phosphate, monobasic, 0.92 mL 2M Sodium Hydroxide solution, 0.953 g NaCl. Total volume 100 mL.

- pH: Target: 9.0; Measured: 9.00
- Type and final molarity of buffer: Boric acid/Sodium hydroxide, 0.30M
- Composition of buffer: 0.312 g boric acid, 0.440 mL 2M Sodium Hydroxide solution, 1.413 g NaCl. Total volume 100 mL.

- Buffer solutions were sparged with argon gas for a minimum of 5 min to exclude oxygen prior to conducting the test.
- The temperature of each buffer was 2.0±0.1°C
- The pH meter was calibrated for use with D2O.
Estimation method (if used):
Not applicable.
Details on test conditions:
oTemperature:  2.0   0.1 oC.  The rationale for performing the hydrolysis at one temperature was to provide the best opportunity to 
slow down the hydrolysis rate and obtain kinetic information.
oThe hydrolysis reactions employed an initial test substance concentration of 1.0   10-3 M. oDue to the hydrolytically unstable nature 
of trimethoxysilane (Kallos et al., 1991), a stock solution in acetonitrile-d3/acetonitrile was used.  oConstant ionic strength of 0.25 M 
was maintained for buffers by the addition of sodium chloride.
o0.05 M buffer solutions were prepared using deuterated water (99.9 atom % D).  Deuterated water (D2O) rather than H2O was used to 
provide a reference frequency lock for the NMR spectrometer and minimize the dynamic range problem introduced by a large solvent peak.
oThe relationship between the pH and pD scales has been established (Glasoe and Long, 1960).  For solutions of comparable acidity or 
basicity, the pH meter reading in D2O solutions is 0.40 pH units lower than in H2O solutions when calibrated against aqueous buffer 
standards.  Therefore, pD = pH meter reading + 0.40 pH units.  The relationship is independent of whether the internal solution of the
electrode contains H2O or D2O.
oBuffer solutions were sterilized by filtering through 0.20 um cellulose nitrate membrane. oThe pH of each buffer solution was measured 
with a calibrated pH meter (using aqueous pH buffers) at 2.0   0.1 oC and then converted to pD values.  This provided a D+ concentration 
equivalent to the H+ concentration at pH 4, 7, and 9. oVessels:  50-mL sterile polypropylene centrifuge tubes. oCo-solvent:  
<1% acetonitrile (~50:50 mixture of deuterated and non-deuterated acetonitrile).

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: 50 mL sterile polypropylene centrifuge tubes with caps.
- Sterilisation method: Nalgene sterile filtration units with 0.2µm cellulose nitrate membrane were used to sterilize the buffers.
- Measures to exclude oxygen: Prior to use, all buffer solutions were sparged with argon gas for a minimum of 5 min to exclude oxygen and carbon dioxide.
- Details on test procedure for unstable compounds: The test substance is unstable with respect to moisture. Items used to prepare the test substance stock solution were oven dried to remove trace moisture. Syringes were dried in a Hamilton syringe heater with aspirator. The acetonitrile used to make up the test substance solution was distilled over P2O5 and stored over molecular sieves to remove trace moisture. The stock solution was prepared inside a nitrogen gas purged glove bag and stored in 22-mL plastic vials with septum lined open-top caps. When not in use, the stock solution was stored in a secondary air tight container with Drierite. The test substance solution in acetonitrile was added directly to the buffer solution at the start of the hydrolysis experiment.
- Details of traps for volatile, if any: None
- If no traps were used, is the test system closed/open: Closed, although caps were removed for sampling.
- Is there any indication of the test material adsorbing to the walls of the test apparatus?: No

TEST MEDIUM
- Volume used/treatment: 800µL of the 0.1035 M solution of the test substance in acetonitrile-d3/acetonitrile was added to 25 mL of each buffer.
- Kind and purity of water: Deuterated water, D2O.
- Preparation of test medium: A 0.1M stock solution of the test substance in acetonitrile was prepared. This was injected directly into the buffer solution at the start of the hydrolysis experiment because the test substance is highly unstable in water.
- Renewal of test solution: Not applicable.
- Identity and concentration of co-solvent: Acetonitrile (0.98%)
Number of replicates:
Replicates:  Two at pD 4.02, 7.00, and 9.00.
Positive controls:
no
Negative controls:
yes
Remarks:
The stock solution of the test substance in acetonitrile was analyzed by 1H-NMR before and after the hydrolysis kinetic experiments to ensure the purity and integrity of trimethoxysilane in the solvent. Stock solution integrity was maintained throughout t
Statistical methods:
Descriptive statistics were performed.
Preliminary study:
The substance is known to be unstable at environmentally relevant temperatures, therefore, no preliminary study was required.
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: Decrease in the 1H-NMR peak for MeO-Si (in the test substance) and increase in the peak due to methanol (transformation product) were measured during the test. Complete disappearance of the test substance was observed.
- Pathways for transformation: Due to the limitation imposed by the rapid hydrolysis, only the total hydrolysis could be studied.
% Recovery:
0
pH:
4
Temp.:
2 °C
Duration:
1.5 min
% Recovery:
0
pH:
7
Temp.:
2 °C
Duration:
2 min
% Recovery:
0
pH:
9
Temp.:
2 °C
Duration:
1.5 min
pH:
4
Temp.:
2 °C
DT50:
<= 0.2 min
Remarks on result:
other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material.
pH:
7
Temp.:
2 °C
DT50:
<= 0.3 min
Remarks on result:
other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material.
pH:
9
Temp.:
2 °C
DT50:
<= 0.2 min
Remarks on result:
other: This value represents an estimated upper limit of the hydrolysis half-life. It refers to disappearance of the test material.
Other kinetic parameters:
None determined.
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

MAJOR TRANSFORMATION PRODUCTS
The increase in methanol during the hydrolysis experiment was observed but not quantified.

In all kinetic experiments, trimethoxysilane was completely hydrolyzed by the time the first 1H NMR spectrum was acquired.  Initial spectra were acquired after 90-144 seconds.

Rate constants and half-lives could not be determined quantitatively, although the data is certainly adequate for
estimating the upper limit of t1/2. The half-life was estimated based on the elapsed time to the initial spectrum.

Table 1 shows the results for each experiment.

Table 1. Results

pH

Replicate Elapsed time Estimated half-life* Average half-life  

4

A 98 14.0 14.1

4

B 99 14.1 14.1

7

A 144 20.6 17.0
 7  B 94 13.4 17.0
 9  A 103 14.7 13.8
 9  B  90 12.9 13.8

* [elapsed time / s] / 7


Since the hydrolysis was so rapid, there was insufficient data to determine rate constants (k1, k2, and k3) for the
sequential hydrolysis reactions of each methoxy group by regression modeling.

First order or pseudo-first order behavior could not be confirmed because:  a) the analytical method was unable to
follow the decrease of the parent peak intensity from the test substance or the increase of peak intensity from the
hydrolysis co-product (methanol) due to a rapid hydrolysis reaction, b) no data points were obtained during the
critical portion of the hydrolysis process (20   70% hydrolyzed), and c) the relationship between k1, k2, and k3
is not known.


Validity criteria fulfilled:
yes
Conclusions:
A hydrolysis half-life of ≤17 s at pH 4, 7 and 9 and 2°C was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Description of key information

Hydrolysis half-life: 11.3 min at pH 7 and 25°C (modified OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:
11.3 min
at the temperature of:
25 °C

Additional information

A hydrolysis half-life of 11.3 min at pH 7 and 25°C was obtained for the submission substance in a modified study conducted according to OECD 111; extra co-solvent was added because the substance has low solubility in water (13 mg/l at 25°C). The half-life refers to disappearance of parent substance. The study also measured the half-life of a reference substance, hexamethyldisiloxane (HMDS, CAS No: 107-46-0), for which a standard OECD 111 study is available. The half-lives for this substance at pH 7 and 25°C under standard and non-standard (10% acetonitrile co-solvent) conditions were 5 days and 11.5 days respectively. This suggests that the half-life for the submission substance, 1,1,3,3-tetramethyldisiloxane (H2-L2), under standard conditions could be less than that measured in the non-standard study. Therefore, a half-life of ≤11.3 minutes at pH 7 and 25°C under the standard conditions of the OECD 111 study is estimated. The chemical safety assessment is not sensitive to variations in the hydrolysis half-life within this range and the measured half-life of 11 minutes is used as the key value.

H2-L2 may theoretically undergo two consecutive reactions in water: hydrolysis of the siloxane (Si-O-Si) group and hydrolysis of the Si-H bond. The latter reaction would produced hydrogen gas as a co-product of hydrolysis. The formation of gas was monitored by head-space analysis. Very little hydrogen was evolved on the time-scale of the degradation of the parent substance. A half-life of 2.5 days was obtained for the degradation of the intermediate hydrolysis product.

Therefore, it is postulated that:

- Initial removal of parent substance is associated with breaking of the siloxane bond to give dimethylsilanol: H(CH3)2SiOSi(CH3)2H → 2 H(CH3)2SiOH. This reaction has a half-life at pH 7 and 25°C of 11.3 minutes.

- The Si-H bond then hydrolyses more slowly (half-life 2.5 days) to give dimethylsilanediol and hydrogen: H(CH3)2SiOH + H2O → (CH3)2Si(OH)2 + H2

In the absence of more specific information, the well-defined half-life for removal of parent compound is applied for general use in the chemical safety assessment, along with the apparent half-life for the second step of reaction where needed.

In addition to the measured result, the hydrolysis half-lives of H2 -L2 at various pHs have been estimated using a validated QSAR estimation method. Half-life values of 0.1 h at pH 4, 0.2 h at pH 5, 1 h at pH 7 and 0.02 h at pH 9 and 20 - 25°C were obtained for H2-L2.

Hydrolysis of the read-across substance hexamethyldisiloxane (HMDS, CAS No. 107-46-0)

Data for the substance hexamethyldisiloxane, HMDS (CAS No. 107-46-0) are read-across to the submission substance H2-L2 for appropriate endpoints (see Section 1.4 of the CSR).The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For HMDS, hydrolysis half-lives at 25°C of 1.4 h at pH 5, 120 h at pH 7 and 12.4 h at pH 9 were determined in accordance with OECD 111 and in compliance with GLP (Dow Corning Corporatin 2006). At pH 4, hydrolysis half-life of 1.5 h at 20 -25°C was obtained for HMDS using a validated QSAR estimation method.

The ultimate hydrolysis product is trimethylsilanol.  

Hydrolysis of the read-across substance 2,4,6,8-tetramethylcyclotetrasiloxane (CAS No. 2370-88-9)

Data for the substance 2,4,6,8-tetramethylcyclotetrasiloxane (CAS No. 2370-88-9) are read-across to the submission substance H2-L2 for appropriate endpoints (see Section 1.4 of the CSR).The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For 2,4,6,8-tetramethylcyclotetrasiloxane, hydrolysis half-life at 22.5°C of approximately 2.2 minutes at pH 7 was obtained using a relevant test method (Dow Corning Corporation 2010). This is supported by predicted half-lives of 0.01 h at pH 4; 0.03 h at pH 5, 0.02 h at pH 7 and 0.08 h at pH 9 and 20-25°C obtained using validated QSAR estimation methods.

The ultimate hydrolysis products are methylsilanetriol and hydrogen.   

Hydrolysis of the read-across substance dichloro(methyl)silane (CAS No. 75-54-7)

Data for the substance dichloro(methyl)silane (CAS No. 75-54-7) are read-across to the submission substance H2-L2 for appropriate endpoints (see Section 1.4 of the CSR). The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate Sections of the CSR for each endpoint.

For dichloro(methyl)silane, hydrolysis half-lives are read-across from dichloro(dimethyl)silane (CAS 75-78-5). Half-lives of approximately 0.2 minutes at pH 4, approximately 0.3 minutes at pH 7 and approximately 0.1 minutes at pH 9 and 1.5°C were obtained in accordance with a relevant test method (Miller 2001). These half-lives relate to degradation of the parent substance to give methylsilanediol and hydrochloric acid. The Si-H bond of methylsilanediol is expected to react in water, forming methylsilanetriol. The rate of this reaction is uncertain.

Since rate of hydrolysis is faster at increased temperatures, at ambient conditions (20 - 25°C), relevant to the environment, the hydrolysis half-lives are expected to be faster. Therefore, half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C may be calculated in the same way as for the submission substance above. As a worst case they are considered to be approximately 5 seconds.

 

The ultimate hydrolysis products are methylsilanetriol and hydrochloric acid.

At concentrations above about 1000-2000 mg/l, condensation products of methylsilanediol and methylsilanetriol can also form.