3-(dimethoxymethylsilyl)propanethiol

Hydrolysis

Description of key information

Hydrolysis half-life: 1.4 h at pH 7 , 0.1 h at pH 4, 0.03 h at pH 9 and 20-25°C (QSAR)

 

Key value for chemical safety assessment

Half-life for hydrolysis:

1.4 h

at the temperature of:

25 °C

Additional information

Hydrolysis half-lives of 0.1 h at pH 4, 0.2 h at pH 5, 1.4 h at pH 7 and 0.03 h at pH 9 and 20-25°C were obtained for the substance using a validated QSAR method. The result is considered to be reliable.

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 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. This is supported by studies for various organosilicon compounds in which calculation of k_H3O+ and k_OH- from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7.

 

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 3-[dimethoxy(mehtyl)silyl]propanethiol 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 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 3-[dimethoxy(methyl)silyl]propanethiol the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 0.52 hours. At pH 2 and 37.5°C the half-life is approximately 5 seconds.

The hydrolysis products are 3-(dihydroxymethylsilyl)propanethiol and methanol.

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 3-trimethoxysilylpropane-1-thiol, (CAS 4420-74-0)

Data for the substance 3-trimethoxysilylpropane-1-thiol (CAS 4420-74 -0) are read-across to the submission substance 3 -[dimethoxy(methyl)silyl]propane-1 -thiol for appropriate endpoints. The silanol hydrolysis product and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate sections of the dossier for each endpoint.

For 3-trimethoxysilylpropane-1-thiol (CAS 4420-74-0), hydrolysis half-lives at 20-25°C of 2.6 h at pH 7, 0.2 h at pH 4 and 0.1 h at pH 9 were predicted for the substance using a validated QSAR estimation method. 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 0.002 h (approximately 7 seconds) at pH 2 and 25°C, and approximately 1 hr at pH 7 and 37.5°C. 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 at pH 2 and 37.5°C is approximately 5 seconds.

The hydrolysis products in this case are 3-(trihydroxysilyl)propanethiol and methanol.