Tetramethyl orthosilicate

Hydrolysis

Description of key information

Hydrolysis half-life: <3 min at pH 4,  7 and 9 at ca. 20 - 25°C (measured data)

Key value for chemical safety assessment

Half-life for hydrolysis:

3 min

Additional information

Hydrolysis half-lives of <3 min at pH 4, 7 and 9 were determined at room temperature in a non-guideline study (screening method based on¹H-NMR) conducted according to a generally accepted scientific principle, but not in compliance with GLP. The result is considered reliable and selected as key study. A supporting study of unassignable reliability reported a half-life value of 32 minutes at 37.4°C and pH 5.7. The supporting result is in agreement with the key study, in that hydrolysis is rapid.

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.

 

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^-2 mol 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 tetramethyl orthosilicate at pH 2 is therefore <2 seconds. However, 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 of the substance at pH 2 and room temperature 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) x e^(0.08.(T-X))

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

Thus, for tetramethyl orthosilicate the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is <1 min. 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 aresilicic acid and methanol.

Hydrolysis of the read-across substance Tetraethyl orthosilicate (CAS 78 -10 -4)

Data for the substancetetraethyl orthosilicate (CAS 78-10-4) are read-across to the submission substance for appropriate endpoints (see Section 1.4 of the CSR). The rapid hydrolysis of the two substances is relevant to this read-across, as discussed in the appropriate sections of the CSR for each endpoint.

For tetraethyl orthosilicate, hydrolysis half-lives at 25°C of 0.11 h at pH 4, 4.4 h at pH 7 and 0.22 h at pH 9 were determined in a reliable study conducted according to OECD Guideline 111 (Hydrolysis as a Function of pH), and in compliance with GLP (DCC 2003).

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 0.0011 h (4 seconds) at pH 2 and 25°C, and 1.6 h at pH 7 and 37.5°C. 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 25°C or 37.5°C is approximately 5 seconds.

The hydrolysis products are silicic acid and ethanol.