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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted according to an appropriate OECD test guideline, but not in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
Due to rapid hydrolysis, rate constant for the reaction was not determined
GLP compliance:
no
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling method: ~9.4 ul was measured and transferred into each buffer solution using 25 µl Hamilton Gastight syringes which were dried with dry nitrogen gas prior to use


- Sample storage conditions before analysis: The test substances were transferred from the original bottle inside a nitrogen-purged glove bag and stored in 22-ml amber glass vials equipped with septum lined open-top caps that were sealed with Parafilm.

Buffers:
- pH: 4.06
- Type and final molarity of buffer: Formic Acid / Sodium Hydroxide, 0.20 M
- Composition of buffer: 2.30 acid; 1.4201 g base, 5.2161 g sodium chloride, total volume 250 ml

- pH: 7.14
- Type and final molarity of buffer: Monobasic sodium phosphate / dibasic sodium phosphate, 0.20 M
- Composition of buffer: 2.0386 g acid, 4.6502 g base, 0.5386 g sodium chloride, total volume 250 ml

- pH: 9.13
- Type and final molarity of buffer: Boric acid / sodium hydroxide, 0.30 M
- Composition of buffer: 4.6379 g acid, 1.376 g base, 5.2601 g sodium chloride, total volume 250 ml

Composition of buffer: sodium phosphate monobasic (99.0+%, Sigma, lot 98H0276), sodium phosphate dibasic (99.0+%, Sigma, lot 30K0228), boric acid (99.5+%, Aldrich, lot 08109B1), sodium hydroxide pellets (99.998%, Aldrich, lot 05224K1) and formic acid (96%, Aldrich, lot 02808B1)

Buffers were made on the same day on which they were used. Buffers were not sterilized or degassed. The pH of each buffer solution was measured immediately prior to the kinetic experiment for which it was used.
Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: (HDPE) bottles (60-ml Fisher Scientific) with screw caps

- Sterilisation method: none

- Measures taken to avoid photolytic effects:

- Measures to exclude oxygen: dry nitrogen gas was bubbled into the system

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

- Kind and purity of water: deuterated water (99.9% of D20, - 0.1 % of HOD residual, ISOTEC INC)

Kinetic experiments were conducted in duplicate for pH 4.06, 7.14 and 9.13.

All experiments were conducted at room temperature (approximately 25°C).

All reactions were conducted with an initial test substance concentration of 0.001 M.

The test substance was transferred from its original container inside a nitrogen-purged glove bag and stored in a 22-ml amber glass vial equipped
with septum lined open-top cap sealed with Parafilm. When not in use, the vial was stored in a screw-capped jar filled with Drierite 50 ml aliquots of buffer solution were measured and transferred to 60-ml HDPE bottles using a 10-ml electronic digital Rainin pipette. Each approximately 9.4 µl of MeSi(OAc), was measured and transferred into each buffer solution using 25-µl Hamilton Gastight syringes which were dried with dry nitrogen gas prior to use.

The test substance was injected into the buffer solution and the timer was started. Each test solution was mixed gently by hand for approximately 1-2 seconds immediately after the test substance was injected. Next, 800 µl of the kinetic solution was transferred immediately into a
5 mm NMR tube using a Pasteur glass pipette which was marked to indicate an 800 µl volume. The NMR sample tube was capped and placed in the instrument immediately. The initial spectrum was acquired and further spectra were subsequently acquired at intervals to monitor any change during the hydrolysis reaction.

For given solution conditions, the hydrolysis of test substance was followed to completion as indicated by disappearance of -CH3 peak from -Si(OAc)3 of test substance or appearance of -CH3 peak from HOAc as a hydrolysis co-product. The elapsed time between the addition of the test
substance to the aqueous buffer solution and the first acquired spectrum was used to estimate an upper limit on half-life, t1/2 (seconds), assuming that at least 7 half-lives represents exhaustive hydrolysis.
Temp.:
25
Initial conc. measured:
ca. 9.4 other: µ/L
Number of replicates:
Duplicates
Positive controls:
no
Negative controls:
no
Statistical methods:
The hydrolysis was very rapid and, therefore, there were not enough data to determine half-lives and rate constants using regression modelling. It was also not possible to confirm pseudo first-order behaviour.
Preliminary study:
The preliminary study was not conducted as the substance was known to be hydrolytically unstable.
Transformation products:
yes
No.:
#1
No.:
#2
Details on hydrolysis and appearance of transformation product(s):
The increase in acetic acid concentration was followed using 1H-NMR.
The hydrolysis reaction is as follows:
MeSi(OAc)3 -> MeSi(OH)3 + 3HOAc
Key result
pH:
4.06
Temp.:
25 °C
DT50:
< 0.2 min
Remarks on result:
other: Estimated based on complete hydrolysis by the time the first 1H-NMR spectrum was acquired.
Key result
pH:
7.14
Temp.:
25 °C
DT50:
< 0.2 min
Remarks on result:
other: Estimated based on complete hydrolysis by the time the first 1H-NMR spectrum was acquired.
Key result
pH:
9.13
Temp.:
25 °C
DT50:
< 0.2 min
Remarks on result:
other: Estimated based on complete hydrolysis by the time the first 1H-NMR spectrum was acquired.
Other kinetic parameters:
Due to the very rapid hydrolysis of the test substance, rate constant was not determined

The substance was completely hydrolysed by the time the first 1H-NMR spectrum was acquired in all tests. The upper limit half-life estimates were <13 seconds at pH 4.06, 7.14 and 9.13 and 25°C. Initial spectra were acquired after 77 -100 seconds and 7 -8 spectra were then acquired at 15 second intervals. No change was observed in subsequent spectra.

Table 1: Results of kinetic experiments

Buffer solution pH before hydrolysis study

Buffer solution pH after hydrolysis study

Temperature from pH Meter (°C)

Kinetic Solution ID

Elapsed Time (seconds)

Estimated half-life (seconds)

Average estimated half-life (seconds)

4.06

4.06

23.2

1

80

11.4

11.9

4.06

4.07

23.2

2

86

12.3

11.9

7.14

7.12

23.0

1

77

11.0

12.0

7.14

7.11

22.9

2

90

12.9

12.0

9.13

9.11

23.6

1

84

12.0

12.1

9.13

9.10

23.4

2

85

12.1

12.1

Conclusions:
A hydrolysis half-life of <12 seconds at pH 4, 7, 9 and 25°C was determined for the substance using an appropriate test method, the result is considered reliable.

Description of key information

Hydrolysis half-life: <12 seconds at pH 4, pH 7 and pH 9 and 25°C (OECD 111)

Key value for chemical safety assessment

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

Additional information

Hydrolysis half-lives of <12 seconds (<0.2 minutes) at pH 4, pH 7 and pH 9 and 25°C were determined for the substance in a study conducted according to OECD 111, but not in compliance with GLP (Dow Corning Corporation 2001a). In all the experiments, the test substance was observed to be completely hydrolysed by the first time the 1H-NMR spectrum was acquired and remained unchanged thereafter. The initial spectrum was acquired after 77-100 seconds and 7-8 spectra were acquired subsequently after an interval of 15 seconds. Due to very rapid hydrolysis, rate constants and half-lives could not be quantitatively determined, although the result is considered adequate to estimate the upper limit of hydrolysis half-life. The result is considered to be reliable and is selected as key study.

In another reliable supporting study conducted according to generally accepted scientific principles, the test substance was found to be hydrolytically unstable under conditions designed to simulate the human stomach (at pH 1.29 and 37°C) (Dow Corning Corporation 2002a). The study was conducted in 0.1 N HCl aqueous solutions using Gel Permeation Chromatography (GPC) to determine the relative molecular weight of the hydrolysis products after 1 and 4 hours reaction time. At the 1 hour reaction time, number-average and weight-average molecular weight of 1247 and 6208 g/mol respectively were found and 69% of the molecular weight were higher than 1000. After 4 hours reaction time, the number-average and weight-average molecular weight increased to 1629 and 152600 g/mol respectively, with 77% of the molecular weights higher than 1000.

The supporting result confirms that hydrolysis is rapid and that under these conditions, there is potential for the formation of polymers.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered. For an acid-base catalysed reaction in buffered solution, the measured rate constant is a linear combination of terms describing contributions from the uncatalyzed reaction as well as catalysis by hydronium, hydroxide, and general acids or bases.

kobs= k0+ kH3O+[H3O+] + kOH-[OH-] + ka[acid] + kb[base]

 

At extremes of pH and under standard hydrolysis test conditions, it is reasonable to suggest that the rate of hydrolysis is dominated by either the hydronium or hydroxide catalysed mechanism.

 

Therefore, at low pH:

kobs˜kH3O+[H3O+]

 

At pH 4 [H3O+] = 10-4 mol dm-3 and at pH 2 [H3O+] = 10-2 mol dm-3; therefore, kobs at pH 2 should be approximately 100 times greater than kobs at pH 4.

 

The half-life of a substance at pH 2 is calculated based on:

t1/2(pH 2) = t1/2(pH 4) / 100

The calculated half-life of methylsilanetriyl triacetate at pH 2 is therefore <0.002 minutes (<0.12 seconds). However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 7 and 25°C is approximately 5 seconds.

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT50(XºC) = DT50(T) * e(0.08.(T-X))

Where T = temperature for which data are available and X = target temperature.

Thus, for methylsilanetriyl triacetate, the calculated hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is <4.4 seconds. Thus, as discussed above, the half-life is considered to be approximately 5 seconds. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half -life is therefore approximately 5 seconds.

The hydrolysis products are methylsilanetriol and acetic acid.

The hydrolysis half-lives of other substances used for read-across in other areas are discussed below:

Hydrolysis of the read-across substance trimethoxy(methyl)silane (CAS 1185-55-3)

Data for the substance, trimethoxy(methyl)silane (CAS 1185-55-3) are read-across to the submission substance methylsilanetriyl triacetate for short-term toxicity to fish, short-term toxicity to aquatic invertebrates, toxicity to aquatic algae and toxicity to microorganisms endpoints. Both substances form the same silanol hydrolysis product which is relevant to this read-across as discussed in appropriate sections for each endpoint.

For trimethoxy(methyl)silane, hydrolysis half-lives at 25°C of <0.033 h at pH 4, 2.2 h at pH 7 and 0.11 h at pH 9 were determined for the substance in accordance with OECD 111 and in compliance with GLP. In a supporting reliable study, the stability of the substance in aqueous media under physiological conditions was investigated. The rates of hydrolysis of 1000 ppm trimethoxy(methyl)silane were determined in water at pH 5.7, 0.15 molar (M) sodium-phosphate buffer (PBS), and 10% rat  serum in  0.15M PBS at pH 7.4 and 37.4°C in soft glass reactors. In this study, the substance was hydrolysed in water, PBS, and PBS plus 10% rat serum at pH 7.4 and 37°C with half-lives of 24, 6.7 and 8.6 minutes respectively. This is also supported by a result in secondary literature of non assignable reliability, which reports a half-life of 23 minutes at pH 5.7 and 37.4°C.

In another supporting study (CRL 2017), the hydrolysis of trimethoxy(methyl)silane was investigated under conditions designed to mimic the rat stomach after dosing the substance in corn oil. The half-life for disappearance of trimethoxy(methyl)silane applied in corn oil to gastric simulation buffer was 33 mins at pH 3 and 37°C and appears to be determined by phase transfer. The data suggest that, in the investigated system, hydrolysis occurs rapidly once trimethoxy(methyl)silane comes into contact with the aqueous layer and the rate determining step is the transfer of the trimethoxy(methyl)silane from the corn oil to the water. Combined recoveries of trimethoxy(methyl)silane and methanol (in mole equivalents of trimethoxy(methyl)silane; 3 moles methanol to 1 mole trimethoxy(methyl)silane assumed) were 87.5 to 104% and methanol content increased proportionally to the decrease in trimethoxy(methyl)silane. The study was conducted according to an appropriate test protocol and is considered reliable.

The 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 registration substance above. This gives a half-life of 0.00033 h (approximately 1 second) at pH 2 and 25°C; however, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and 37.5°C is approximately 5 seconds.

 

At pH 7 and 37.5°C, the half-life is 0.8 h. At pH 2 and 37.5°C, the half-life is approximately 5 seconds as a worst-case.

The hydrolysis products are methylsilanetriol and methanol.

Hydrolysis of the read-across substance triacetoxyethylsilane (CAS 17689-77-9)

Data for the substance triacetoxyethylsilane (CAS 17689-77-9) are read-across to the submission substance methylsilanetriyl triacetate for biodegradation in water and repeated dose toxicity - oral endpoints. The hydrolysis half-life and the silanol hydrolysis products of the two substances is relevant to this read-across as discussed in appropriate section for each endpoint.

For triacetoxyethylsilane, hydrolysis half-lives at 25°C of <0.2 minutes at pH 4, pH 7 and pH 9 were determined in accordance with OECD 111 (Dow Corning Corporation 2001b).  

The 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 registration substance above. This gives a half-life of 0.002 minutes (<0.12 seconds) at pH 2 and 25°C, however, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and 25°C is approximately 5 seconds. At pH 2 and 37.5°C and pH 7 and 37.5°C, it is not appropriate to apply any further correction, the half-life is therefore approximately 5 seconds.

The hydrolysis products are ethylsilanetriol and acetic acid.

Hydrolysis of the read-across substance triethoxy(methyl)silane (CAS 2031-67-6)

Data for the substance triethoxy(methyl)silane (CAS 2031-67-6) are read-across to the submission substance methylsilanetriyl triacetate for short-term toxicity to fish, short-term toxicity to aquatic invertebrates, toxicity to aquatic algae and genetic toxicity in vitro endpoints.The hydrolysis half-life and the silanol hydrolysis product of the two substances is relevant to this read-across as discussed in the appropriate sections for each endpoint.

For triethoxy(methyl)silane, hydrolysis half-lives of 0.3 h at pH 4, 5.5 h at pH 7 and 0.1 h at pH 9 and 20 -25°C were determined in using a validated QSAR estimation method.

The hydrolysis products are methylsilanetriol and ethanol.

Hydrolysis of the read-across substance trichloromethylsilane (CAS 75-79-6)

Data for the substance trichloromethylsilane (CAS 75-79-6) are read-across to the submission substance methylsilanetriyl triacetate for mammalian mutagenicity endpoint. The hydrolysis half-lfe and the silanol hydrolysis product of the two substances is relevant to this read-across as discussed in the appropriate sections for each endpoint.

For trichloro(methyl)silane, hydrolysis half-lives at 1.5°C of <1 minute at pH 4, pH 7 and pH 9 were determined in accordance with OECD 111. (Dow Corning Corporation 2001c).

 

The 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 based on the predicted half-lives in the same way as for the registration substance above.The calculated half-life of trichloro(methyl)silane at pH 2 is therefore =0.1 second at 1.5°C. However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and 1.5°C is approximately 5 seconds.

 

Thus, for trichloro(methyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is =1 second, so a worst-case half-life of approximately 5 seconds is used.

 

The half-lives at pH 2 and 37.5°C (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half-life is therefore approximately 5 seconds.

 

The half-lives at pH 4 and 37.5°C, the calculated half-life is =0.5 second, so worst case half-life of approximately 5 seconds is used. At pH 5.5 and 37.5°C (relevant for dermal exposure), the hydrolysis half-life will be between the half-lives at pH 4 and pH 7 and 37.5°C, and thus half-life of approximately 5 seconds is used as a worst case.

 

The hydrolysis products are methylsilanetriol and hydrochloric acid.

Hydrolysis of the read-across substance trichloro(ethyl)silane (CAS 115-21-9)

Data for the substance trichloro(ethyl)silane (CAS 115-21-9) are read-across to the submission substance methylsilanetriyl triacetate for long-term toxicity to aquatic invertebrates endpoint. The silanol hydrolysis product of the two substances are relevant to this read-across as discussed in the appropriate section for the endpoint.

For trichloro(ethyl)silane, hydrolysis half-lives at 1.5°C of <1 minute at pH 4, pH 7 and pH 9 were read-across from the study on the analogue substance, trichloro(methyl)silane (Dow Corning Corporation 2001).

The hydrolysis products are ethylsilanetriol and hydrochloric acid.