3-(dimethoxymethylsilyl)propyl methacrylate

Hydrolysis

Description of key information

Hydrolysis half-life: 0.1 h at pH 4, 0.2 h at pH 5, 1.5 h at pH 7 and 0.03 h at pH 9 and 20-25°C (QSAR) (for the methoxysilane groups).

Key value for chemical safety assessment

Half-life for hydrolysis:

1.5 h

at the temperature of:

25 °C

Additional information

The registration substance, 3-[dimethoxy(methyl)silyl]propyl methacrylate contains two types of hydrolysable groups: two methoxysilane groups (which react to the corresponding silanols plus methanol) and one methacrylate ester group (which has the potential to react to the corresponding alcohol plus methacrylic acid). 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-lives of 0.1 h at pH 4, 0.2 h at pH 5, 1.5 h at pH 7 and 0.03 h at pH 9 and 20-25°C were determined for the substance using a validated QSAR estimation 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 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 0.001 h (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. The half-life is therefore reported as 5 seconds 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°C) * e^(0.08.(T-X))

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

Thus, for 3-[dimethoxy(methyl)silyl]propyl methacrylate the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 0.55 hours. 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 in this case are 3-[dihydroxy(methyl)silyl]propyl methacrylate and methanol.

Note on hydrolysis of the methacrylate ester group:

Very limited evidence of the hydrolysis of the methacrylate ester group is available. The hydrolysis half-life of methyl methacrylate (a much more soluble substance) is reported to be >1 year at 25°C and pH 7 and 14.4 days at 25°C and pH 9 (WHO CICAD summary citing Howard, 1989). In the case of the registration substance 3-[dimethoxy(methyl)silyl]propyl methacrylate, the reaction is expected to be slower due to the steric effects of the 3 -[dimethoxy(methyl)silyl propyl group (Mabey and Mill 1978). For the purposes of chemical safety assessment, in the absence of clear evidence it is considered that the hydrolysis of the methacrylate ester group is not significant for the exposure assessment at any relevant pH. Therefore, where the chemical safety assessment considers hydrolysis products, these are identified as 3-[dihydroxy(methyl)silyl]propyl methacrylate and methanol. The same assumptions are made for read-across substances containing methacrylate groups. This is a conservative position in the absence of clear evidence, as the methacrylate structural feature is likely to be more toxic than the corresponding alcohol.

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-trimethoxysilylpropyl methacrylate CAS No. 2530-85-0

Data for the substance 3-trimethoxysilylpropyl methacrylate (CAS No. 2530-85-0) are read-across to the submission substance 3-[dimethoxy(methyl)silyl]propyl methacrylate 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 for each endpoint.

Hydrolysis half-lives of 0.018 h at pH 4, 1.87 h at pH 7, and 0.068 h at pH 9 and 20°C were determined for the substance in accordance with OECD 111 Test Guideline and in compliance with GLP (Lange, 2016). Also, predicted hydrolysis value of 0.3 h at pH 4, 0.3 h at pH 5, 4.4 h at pH 7 and 0.1 h at pH 9 at 20 -25°C were obtained for the substance using a validated QSAR estimation method. Similarly, hydrolysis half-lives of 3 h at 25°C and pH 7 and 4 h at 20°C and pH 7 were determined in a preliminary study conducted in accordance with OECD 111 and in compliance with GLP. At pH 4 and pH 9, the test substance was observed to undergo rapid hydrolysis and as such half-lives at these pHs was estimated to be < 1 hour. In a secondary source to which reliability could not be assigned, a hydrolysis half-life of 121.6 minutes (approximately 2 hours) at pH 4.5 and 25°C was reported for the substance. The available data are in agreement that the substance undergoes rapid hydrolytic degradation.

The half-lives at pH 2 and 20°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 0.00018 h (approximately 1 seconds) at pH 2 and 25°C. However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5 -10 seconds. The half-life is therefore reported as 5 seconds as a worst case. At pH 7 and 37.5°C, the hydrolysis half-life is 0.46 hours. At pH 2 and 37.5°C; the half-life is approximately 5 seconds.

At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC.

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

Hydrolysis of the read-across substance (trimethoxysilyl)methyl methacrylate CAS No. 54586 -78 -6)

Data for the substance (trimethoxysilyl)methyl methacrylate (CAS No. 54586 -78 -6) are read-across to the submission substance 3-[dimethoxy(methyl)silyl]propyl methacrylate 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 for each endpoint.

Hydrolysis half-lives of 0.3 h at pH 4, 0.3 h at pH 5, 4.2 h at pH 7 and 0.1 h at pH 9 and 20-25°C 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 0.003 h (approximately 11 seconds) at pH 2 and 25°C, and approximately 1.5 h at pH 7 and 37.5°C. 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 be considered that the half-life for the substance at pH 2 and 37.5°C is approximately 5 seconds.

At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC (0.1 - 1.5 hours).

The hydrolysis products in this case are (trihydroxysilyl)methyl methacrylate and methanol.

Hydrolysis of the read-across substance 3-(chlorodimethylsilyl)propyl methacrylate (CAS No. 24636-31-5)

Data for the substance 3-(chlorodimethylsilyl)propyl methacrylate (CAS No. 24636-31-5) are read-across to the submission substance 3-[dimethoxy(methyl)silyl]propyl methacrylate for appropriate endpoints.The 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-(chlorodimethylsilyl)propyl methacrylate, hydrolysis half-lives are read-across from analogue trichlorosilane substances. Half-life value of <1 minute at pH 4, pH 7 and pH 9 and 1.5°C were determined in accordance with OECD 111 (Dow Corning Corporation 2001).

 

The hydrolysis products are 3-[hydroxy(dimethyl)silyl]propyl methacrylate and hydrochloric acid.

Hydrolysis of the read-across substance 3-[dimethoxy(methyl)silyl]propyl acrylate CAS No. 13732-00-8)

Data for the substance, 3-[dimethoxy(methyl)silyl]propyl acrylate (CAS No. 13732-00-8) are read-across to the submission substance 3-[dimethoxy(methyl)silyl]propyl methacrylate 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 for each endpoint.

Hydrolysis half-lives of 0.2 h at pH 4, 0.2 h at pH 5, 1.7 h at pH 7 and 0.04 h at pH 9 and 20-25°C 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. 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 be considered that the half-life for the substance at pH 2 and 25°C is approximately 5 seconds. At pH 7 and 37.5°C, the half-life is 0.63 hours and at pH 2 and 37.5°C, the half-life is approximately 5 seconds as a worst-case.

At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 5 and pH 7 at 37.5ºC (0.07 - 0.63 hours).

The hydrolysis products in this case are 3-[dihydroxy(methyl)silyl]propyl acrylate and methanol.

Hydrolysis of the read-across substance [dimethoxy(methyl)silyl]methyl methacrylate CAS no. 121177-93-3

Data for the substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS no. 121177-93-3) are read-across to the registration substance, 3-(chlorodimethylsilyl)propyl methacrylate 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 for each endpoint.

Hydrolysis half-lives of 1.8 h at pH 7, 0.2 h at pH 4, 0.04 h at pH 9 and 20-25°C 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 CAS No. 2530-85-0 above. This gives a half-life of 0.002 h (approximately 7 seconds) at pH 2 and 25°C. 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 be considered that the half-life for the substance at pH 2 and 25°C is approximately 5 seconds. At pH 7 and 37.5°C, the half-life is 0.66 hours and at pH 2 and 37.5°C, the half-life is approximately 5 seconds as a worst-case. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC (0.07 - 0.66 hours).

The hydrolysis products in this case are [dihydroxy(methyl)silyl]methyl methacrylate and methanol.

Reference:

Mabey W, Mill T (1978). Critical review of hydrolysis of organic compounds in water under environmental conditions. Journal of Physical and Chemical reference data. Washington D.C, American Chemical Society, vol. 7, pages 383-415.