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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
(Q)SAR
Adequacy of study:
key 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:
See attached QMRFs/QPRFs
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 di- and tri-alkoxysilanes. It is a multiple linear regression based model with descriptors representing (i) steric effects of the alkoxy group, (ii) steric effects of the side-chain(s), and (iii) electronic effects of the side-chain(s).

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.
Transformation products:
yes
No.:
#1
No.:
#2
Key result
pH:
4
DT50:
0.4 h
Remarks on result:
other: 20-25°C
Key result
pH:
5
DT50:
0.5 h
Remarks on result:
other: 20-25°C
Key result
pH:
7
DT50:
11.7 h
Remarks on result:
other: 20-25°C
Key result
pH:
9
DT50:
0.2 h
Remarks on result:
other: 20-25°C
Conclusions:
Hydrolysis half-life values at 20-25°C of 11.7 h at pH 7, 0.4 h at pH 4, 0.5 h at pH 5 and 0.2 h at pH 9 were obtained using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis half-lives: 0.4 h at pH 4, 0.5 h at pH 5, 11.7 h at pH 7 and 0.2 h at pH 9 and 20-25°C (QSAR).

Key value for chemical safety assessment

Additional information

The registration substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane contains two types of hydrolysable groups: two ethoxy groups (which react to the corresponding silanols plus ethanol) and one epoxide ring (which has the potential to react to the corresponding diol). The chemical safety assessment of the substance assumes that these reaction processes will proceed independently based on their rates under the relevant conditions.

Hydrolysis of the ethoxysilane groups:

Hydrolysis half-life values of 0.4 h at pH 4, 0.5 h at pH 5, 11.7 h pH 7 and 0.2 h at pH 9 and 20-25°C were obtained for hydrolysis of the alkoxysilane (ethoxy) functional groups in the registration substance using an accepted validated QSAR method.

This is supported by an experimental result read-across from a structurally analogous substance. A hydrolysis half-life of 36 h at pH 7 and 25°C was determined in a reliable study with [3-(2,3-epoxypropoxy)propyl]triethoxysilane (CAS No: 2602-34-8), conducted in accordance with OECD 111 and in compliance with GLP. At pH 9.0, the half-life was found to be <2.4 h at 50 °C and estimated to be <1 day at 25 °C. At pH 4.0, the test substance was found to be insoluble. The hydrolysis study focuses on removal of parent. The products were not identified in the study and it is unclear which reaction(s) the stated half-lives relate to. The authors of this summary consider that this could reflect rapid hydrolysis followed by polymerisation of the hydrolysis product.

As the alkoxysilane group 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+] =10-4mol dm-3and at pH 2 [H3O+] =10-2mol dm-3; therefore, kobs at pH 2 should be approximately 100 times greater than kobsat 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 reaction of the ethoxy groups in [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane at pH 2 is therefore 0.004 hours (approximately 14 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 reaction of the ethoxy groups in [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 4.4 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is approximately 5 seconds.

The hydrolysis products in this case are (2,3-epoxypropoxy)propylmethylsilanediol and ethanol. The ultimate hydrolysis products will be 3-{3-[dihydroxy(methyl)silyl]propoxy}propane-1,2-diol and ethanol.

Hydrolysis of the epoxide ring:

Very limited evidence of the hydrolysis of the epoxide ring is available. The hydrolysis half-life of the epoxy group of glycidyl alcohol (a much more soluble substance) is reported to be 12 hours at 25°C and pH 7 (HSDB citing Mabey W, Mill T J Phys Chem Ref Data 7: 383-415 (1978). However, in the case of the registration substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane, the reaction may be slower and for the purposes of chemical safety assessment, in the absence of clear evidence it is considered that the epoxide ring-opening is not significant for the exposure assessment at any relevant pH. Therefore, where the chemical safety assessment considers hydrolysis products, these are identified as [3-(2,3-epoxypropoxy)propyl]methylsilanediol and ethanol. This is a conservative position in the absence of clear evidence, as the epoxide structural feature is likely to be more toxic than the corresponding diol.

(Reference:Mabey W. and Mill T. (1978). Critical review of hydrolysis of organic compounds in water under environmental conditions.J. Phys. Chem. Ref. Data,7, 383-415)

Hydrolysis of the read-across substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (CAS 2530-83-8)

Data for the substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (CAS 2530-83-8) are read across to the submission substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane for appropriate endpoints (see Section 1.5 of the CSR). The structural similarity, hydrolysis half-life and 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 [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, hydrolysis half-lives at 24.5°C of 0.15 h at pH 5, 6.5 h at pH 7 and 0.13 h at pH 9 were determined in accordance with OECD 111 (Dow Corning Corporation 2001). The hydrolysis half-life at pH 4 is expected to be faster than at pH 5. Therefore, at pH 4, a conservative half-life of <0.15 h is used.

The half-lives for reaction of the methoxy groups 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 <0.0015 h (<5.4 seconds) at pH 2 and 25°C and 2.4 h at pH 7 and 37.5°C. A half-life of 3.3 h at pH 7 and 37°C was measured in the key study (for the read-across substance) (Dow Corning Corporation 2001). 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 for the substance at pH 2 and 37.5°C is approximately 5 seconds.

The hydrolysis products are (2,3-epoxypropoxy)propylsilanetriol and methanol.

Hydrolysis of the read-across substance [3-(2,3-epoxypropoxy)propyl]triethoxysilane (CAS 2602-34-8)

Data for the substance [3-(2,3-epoxypropoxy)propyl]triethoxysilane (CAS 2602-34-8) are read across to the submission substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane for appropriate endpoints (see Section 1.5 of the CSR). The structural similarity, hydrolysis half-life and 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.

A hydrolysis half-life of 36 h at pH 7 and 25°C was determined in a reliable study conducted in accordance with OECD 111 and in compliance with GLP. At pH 9.0, the half-life was found to be <2.4 h at 50°C and estimated to be <1 day at 25°C. At pH 4.0, the test substance was found to be insoluble. The authors of this summary consider that this observation could be due to rapid hydrolysis followed by polymerisation of the hydrolysis product rather than insolubility of the parent substance. The hydrolysis study focuses on removal of parent. The products were not identified in the study and it is unclear which reaction(s) the stated half-lives relate to.

Hydrolysis half-life values of 0.6 h at pH 4, 0.6 h at pH 5, 25.1 h at pH 7 and 0.4 h at pH 9 and 20-25°C were obtained for the hydrolysis of the alkoxysilane (ethoxy) functional group using an accepted QSAR validation method.

The hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 4 – 13 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is approximately 5 seconds. The hydrolysis products will be (2,3-epoxypropoxy)propylsilanetriol and ethanol.