[3-(2,3-epoxypropoxy)propyl]dimethoxymethylsilane

Hydrolysis

Link to relevant study record(s)

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:

0.1 h

Remarks on result:

other: 20-25°C

Key result

pH:

5

DT50:

0.2 h

Remarks on result:

other: 20-25°C

Key result

pH:

7

DT50:

1.6 h

Remarks on result:

other: 20-25°C

Key result

pH:

9

DT50:

0.03 h

Remarks on result:

other: 20-25°C

Conclusions:

Hydrolysis half-life values at 20-25°C of 0.1 h at pH 4, 0.2 h at pH 5, 1.6 h at pH 7 and 0.03 h at pH 9 were obtained using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis half-life: 0.1 h at pH 4, 1.6 h at pH 7 and 0.03 h at pH 9 and 20-25°C (QSAR).

Additional information

The registration substance [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane contains two types of hydrolysable groups: two methoxy groups (which react to the corresponding silanols plus methanol) 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 methoxysilane groups:

Hydrolysis half-life values of 0.1 h at pH 4, 1.6 h pH 7 and 0.03 h at pH 9 and 20-25°C were obtained for hydrolysis of the alkoxysilane (methoxy) functional groups in the registration substance using an accepted validated QSAR method.

Hydrolysis of the epoxide ring:

No data are available for the rate of hydrolysis of the epoxide ring in [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane. Mabey and Mill 1978 report hydrolysis data for 14 epoxides. The half-lives at pH 7 and 25°C for most of the substances are similar at 14.6 ±4.6 days. Only conjugated epoxides and aromatic epoxides react quickly, with half-lives of a few minutes.

For the purposes of the chemical safety assessment, in the absence of clear evidence it is considered that the epoxide ring-opening is not significant for the registration substance at any relevant pH. Therefore, where the chemical safety assessment considers the hydrolysis products, these are identified as [3-(2,3-epoxypropoxy)propyl]methylsilanediol and methanol. 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. The same assumption is made for the epoxy groups of the read-across substances.

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.

 

k_obs= k₀+ k_H3O+[H₃O⁺] + k_OH-[OH^-] + k_a[acid] + k_b[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:

k_obs≈k_H3O+[H₃O⁺]

 

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

 

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

t_1/2(pH 2) = t_1/2(pH 4) / 100

The calculated half-life for reaction of the methoxy groups in [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane at pH 2 is therefore 0.001 hours (approximately 3.6 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 2 and 20-25°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 reaction of the methoxy groups in [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 0.6 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 for the purposes of CSA will be (2,3-epoxypropoxy)propylmethylsilanediol (1 mole) and methanol (2 moles). The ultimate hydrolysis products will be 3-{3-[dihydroxy(methyl)silyl]propoxy}propane-1,2-diol (1 mole) and methanol (2 moles).

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

Hydrolysis of the read-across substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (CAS No. 2530-83-8)

Data for the substance [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (CAS No. 2530-83-8) are read across to the submission substance [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane for appropriate endpoints. 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 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 the 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 estimated 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 2530 -83 -8) (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 of the substance at pH 2 and 37.5°C is approximately 5 seconds.

The hydrolysis products for the purposes of the CSA will be (2,3-epoxypropoxy)propylsilanetriol (1 mole) and methanol (3 moles). the ultimate hydrolysis products will be 3 -[3-(trihydroxysilyl)propoxy]propane-1,2-diol (1 mole) and methanol (3 moles).

Hydrolysis of the read-across substance [3-(2,3-epoxypropoxy)propyl]triethoxysilane (CAS No. 2897-60-1)

Data for the substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane (CAS No. 2897-60-1) are read-across to the submission substance [3-(2,3-epoxypropoxy)propyl]dimethoxy(methyl)silane for appropriate endpoints. 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.

Hydrolysis half-lives of 0.4 hours at pH 4, 11.7 hours at pH 7 and 0.2 hours at pH 9 and 20-25°C were obtained for the hydrolysis of the alkoxysilane (triethoxy) functional groups using a validated QSAR estimation method.

The half-lives for the reaction of the ethoxy 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 approximately 14 seconds at pH 2 and 20-25°C and 4.4 h at pH 7 and 37.5°C. At pH 2 and 37.5°C, the half-life is approximately 5 seconds.

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

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