Tri(isopropoxy)vinylsilane

Hydrolysis

Description of key information

Hydrolysis half-lives: 0.3 h at pH 4, 0.4 h at pH 5, 7.0 h at pH 7 and 0.1 h at pH 9 and 20-25°C (QSAR)

Additional information

The hydrolysis half-lives of the submission substance, tri(isopropoxy)(vinyl)silane (CAS No. 18023-33-1), have been predicted using a validated QSAR estimation method. Hydrolysis half-lives are estimated to be 0.3 h at pH 4, 7.0 h at pH 7 and 0.1 h at pH 9 and 20-25°C. The uncertainty on the prediction at pH 7 is defined as ±0.5 log units, giving a range of 2-21 h. However, the substance is slightly outside the applicability domain for the prediction defined in the QMRF in that the steric descriptor for the alkoxy groups, SR’, is 2; the defined range is 1 – 1.75. This is because all the alkoxy groups in the training set have linear alkoxy chains, whereas the submission substance has isopropoxy groups. There is some evidence that the presence of a tert-butoxy group slows the hydrolysis rate relative to a n-butoxy group more than the QSAR method would predict. Therefore, it is possible that the branching in the isopropoxy group increases the hydrolysis rate more than is predicted by the QSAR method (although this effect will be less than for the more sterically bulky t-butoxy group). Therefore, there is greater than usual uncertainty in the hydrolysis prediction for this substance.

 

Hydrolysis testing is not a requirement at Annex VII. The available predicted method is sufficient to indicate that hydrolysis is reasonably fast under environmentally relevant conditions.

As the hydrolysis reaction may be acid or base-catalysed, the rate of reaction is expected to be slowest at around 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 uncatalysed 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 ^-4 mol dm^-3 and at pH 2 [H₃O⁺] = 10 ^-2 mol dm^-3; therefore, k_obs at pH 2 should be approximately 100 times greater than k_obs at 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 the substance at pH 2 and 20-25°C is therefore 0.003 h (approximately 11 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°C) * e^(0.08.(T-X))

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

Thus, for the submission substance, the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 2.4 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately 4 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 37.5°C is approximately 5 seconds.

The hydrolysis products in this case are vinylsilanetriol and isopropanol.

The hydrolysis data for substances used in this dossier for read-across purposes for other endpoints are now discussed.

Hydrolysis of the read-across substance trimethoxyvinylsilane (CAS No: 2768-02-7)

Data for the substance trimethoxyvinylsilane (CAS No: 2768-02-7) are read-across to the submission substance tri(isopropoxy)(vinyl)silane for some endpoints. The hydrolysis half-lives and the hydrolysis products of the two substances are relevant for this read-across.

Trimethoxyvinylsilane has measured half-lives of <10 minutes, <2.4 h and <10 minutes at pH 4, pH 7 and pH 9 and 50°C in a preliminary study according to OECD 111. Also, it has predicted half-lives at 20-25ºC of 0.04 h (2 minutes) at pH 4, 0.1 h at pH 5 and 7, and 0.004 h (14 seconds) at pH 9. In a secondary source to which reliability could not be assigned, half-lives of 0.24 h at pH 7 and 0.58 h at pH 4 and 23°C were reported for trimethoxyvinylsialne.

The hydrolysis products are vinylsilanetriol and methanol.

Hydrolysis of the read-across substance tris(2-methoxyethoxy)vinylsilane (CAS No: 1067-53-4)

Data for the substance tris(2-methoxyethoxy)vinylsilane (CAS No: 1067-53-4) are read-across to the submission substance tri(isopropoxy)(vinyl)silane for some endpoints. The hydrolysis half-lives and the hydrolysis products of the two substances are relevant for this read-across.

Tris(2-methoxyethoxy)(vinyl)silane has measured hydrolysis half-lives of 1.6 minutes at pH 4, 61.5 minutes at pH 7 and 0.94 minutes at pH 9 and 25°C were obtained for the substance in accordance with OECD 111 and in compliance with GLP. In order to determine the effect of temperature on hydrolysis rate of the submission substance, additional experiment was conducted at both pH 4 and pH 9 and 10°C and 35°C. At 10°C, hydrolysis half-life values of 3.3 minutes at pH 4 and 3.7 minutes at pH 9 were obtained. Similarly, at 35°C, hydrolysis half-lives of 0.96 minutes at pH 4 and 0.43 minutes at pH 9 were obtained

The hydrolysis products are vinylsilanetriol and 2-methoxyethanol.

Hydrolysis of the read-across substance tris(isopropenyloxy)(vinyl)silane (CAS No: 15332-99-7)

Data for the substance, tris(isopropenyloxy)(vinyl)silane (CAS No: 15332-99-7) are read-across to the submission substance tri(isopropoxy)(vinyl)silane for some endpoints. The hydrolysis half-lives and the hydrolysis products of the two substances are relevant for this read-across.

The hydrolysis half-lives of the read-across substance, tris(isopropenyloxy)(vinyl)silane (CAS No. 15332-99-7), have been predicted using a validated QSAR estimation method. Hydrolysis half-lives are estimated to be ≤0.3 h at pH 4, ≤6.6 h at pH 7 and ≤0.1 h at pH 9 and 20-25°C. As discussed above for the submission substance, there is greater than usual uncertainty associated with this prediction because the training set does not contain any substances with non-linear alkoxy groups. In addition, the training set does not contain any alkenoxy substances (with double bonds in the OR’ group). The predicted values are therefore the same for the read-across substance (OR’ is isopropenyloxy, O(C)C=C) as for the submission substance (OR’ is isopropyloxy, O(C)CC). For the read-across substance the values are considered as upper limits for the hydrolysis half-lives and are reported as ≤ values because:

- The carbon-carbon double bond in the isopropenyloxy side-chain could weaken the Si-O bond electronically.

- The carbon atom of the isopropenyloxy side-chain is sterically less hindering compared to isopropyloxy group.

Both of these effects are expected to speed up the hydrolysis rates of the submission substance.

The half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C are the same as for the submission substance as stated above.

The hydrolysis products are vinylsilanetriol and propen-2-ol. Propen-2-ol is an enol type structure, which is in equilibrium with its keto tautomer, propanone (commonly called acetone). The equilibrium heavily favours the keto form at room temperature. Therefore, the hydrolysis products of [tris(isopropenyloxy)(vinyl)silane] are acetone (3 moles) and vinylsilanetriol (1 mole).