2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane

Hydrolysis

Description of key information

Hydrolysis half-life: 4.1 h at pH 7, 0.2 h at pH 4, 0.3 h at pH 5 and 0.1 h at pH 9 and 20-25°C (QSAR).

Key value for chemical safety assessment

Half-life for hydrolysis:

4.1 h

at the temperature of:

25 °C

Additional information

The registration substance 2-(3,4-epoxycyclohexyl) ethyltrimethoxysilane contains two types of hydrolysable groups: three 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 0.2 h at pH 4, 0.3 h at pH 5, 4.1 h at pH 7 and 0.1 h at pH 9 at 20 -25⁰C were obtained for hydrolysis of the alkoxysilane (methoxy) functional group using an accepted validated QSAR method (Peter Fisk Associates 2014).

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 authors of this summary consider that this observation could reflect rapid hydrolysis followed by polymerisation of the hydrolysis product. 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 of the epoxide ring:

Very limited evidence of the hydrolysis of the epoxide ring is available. In the case of the registration substance 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, 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 2-(3,4-epoxycyclohexyl)ethylsilanetriol 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.

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 of reaction of the ethoxy groups in 2-(3,4-epoxycyclohexyl) ethyltrimethoxysilane at pH 2 is therefore 0.002 hours (approximately 7 seconds). However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5 -10 seconds. Therefore, half-life of approximately 5 seconds is used as a worst case.

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 2-(3,4-epoxycyclohexyl) ethyltrimethoxysilane

the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 1.5 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is less than 5 seconds.

The hydrolysis products will be 2-(3,4 -epoxycyclohexyl)ethylsilanetriol and methanol. The ultimate hydrolysis products will be [3-(2,3-hydroxy)-cyclohexyl)ethyl]silanetriol and methanol.

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 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane for appropriate endpoints (see Section 1.4 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 (Dow Corning Corporation, 2001). It is likely that factors such as diffusion become rate-determining 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 [3-(2,3-epoxypropoxy)propyl]silanetriol and methanol.

Hydrolysis of the read-across substance 2-(3,4-epoxycyclohexyl)ethyltriethoxy silane (CAS 10217-34-2)

Data for the substance 2-(3,4-epoxycyclohexyl)ethyltriethoxy silane (CAS 10217-34-2) are read-across to the submission substance 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane for appropriate endpoints (see Section 1.4 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 2-(3,4-epoxycyclohexyl)ethyltriethoxy silane, hydrolysis half-lives for reaction of the ethoxy groups at 25°C of 0.7 h at pH 4, approximately 31 h at pH 7 and 0.4 h at pH 9 were determined using a validated QSAR estimation method. The pH7 half-life is supported by a reliable OECD 111 study result of 28.6 h and 30.3 h at pH7 and 25°C for the two isomers present. It is not clear in the study which groups were hydrolysing but the half-life is consistent with expectation for the rate of reaction of the ethoxy groups.

The half-lives for 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 0.007 h (25 seconds) at pH 2 and 25°C, 0.0026 h (9 seconds) at pH 2 and 37.5°C and 11 h at pH 7 and 37.5°C.

The hydrolysis products are2-(3,4-epoxycyclohexyl)ethylsilanetrioland ethanol

 

Hydrolysis of the read-across substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane (CAS 2897-60-1)

 

Data for the substance [3-(2,3-epoxypropoxy)propyl]diethoxy(methyl)silane (CAS 2897-60-1) are read-across to the submission substance 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane for appropriate endpoints (see Section 1.4 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.

Hydrolysis of the ethoxysilane groups: Hydrolysis half-lives of 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 were obtained for hydrolysis of the alkoxysilane (ethoxy) functional group using a validated QSAR estimation method. At 37.5°C and pH 7 (relevant for lungs and blood) the calculated hydrolysis half-life is approximately 4.4 hours. At 37.5°C 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)propylmethylsilanediol and ethanol. The ultimate hydrolysis products will be 3-{3-[dihydroxy(methyl)silyl]propoxy}propane-1,2-diol and ethanol.