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Hydrolysis

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Description of key information

Hydrolysis half-lives: 0.018 h at pH 4, 1.87 h at pH 7, and 0.068 h at pH 9 and 20°C

Key value for chemical safety assessment

Half-life for hydrolysis:
1.87 h
at the temperature of:
20 °C

Additional information

The registration substance, 3-trimethoxysilylpropyl methacrylate contains two types of hydrolysable groups: three trimethoxy groups (which react to the corresponding silanols) 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 trimethoxysilane groups:

The hydrolysis of the submission substance has been determined in accordance with OECD 111 Test Guideline and in compliance with GLP. Hydrolysis half-life values are:

pH 4: 0.0165 h at 16.5°C, 0.018 h at 20°C, 0.0155 h at 25°C

pH 7: 2.52 h at 16.5°C, 1.87 h at 20°C, 1.7 h at 25°C

pH 9: 0.0883 h at 16.5°C, 0.068 h at 20°C, 0.0491 h at 25°C

The results are considered to be reliable and are used for assessment purposes.

The key study is supported by two other reliable hydrolysis rates that are available for the substance. Hydrolysis half-lives at 20- 25°C of 0.3 h at pH 4, 0.3 h at pH 5, 4 h at pH 7 and 0.1 h at pH 9 were predicted for the substance using a validated QSAR estimation method. Similarly, hydrolysis half-lives of 3 h at 25°C, 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 mins (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 in contact with water.

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.

kobs= k0+ kH3O+[H3O+] + kOH-[OH-] + ka[acid] + kb[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:

kobs˜kH3O+[H3O+]

At pH 4 [H3O+] = 10 -4 mol dm-3 and at pH 2 [H3O+] = 10-2 mol dm-3; therefore, kobs at pH 2 should be approximately 100 times greater than kobs at pH 4.

The half-life of a substance at pH 2 is calculated based on:

t1/2(pH 2) = t1/2(pH 4) / 100

The calculated half-life of the substance at pH 2 and 20°C is therefore 0.00018 h (approximately 1 second). 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) * e(0.08.(T-X))

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

Thus, for 3-trimethoxysilylpropyl methacrylate the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 0.46 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.

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.

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). However, in the case of the registration substance 3 -trimethoxysilylpropyl methacrylate, the reaction may be slower and for the purposes of chemical safety assessment, in the absence of clear evidence it is considered that the methacrylate ester group reaction is not significant for the chemical safety assessment at any relevant pH. Therefore, where the chemical safety assessment considers hydrolysis products, these are identified as 3-(trihydroxysilyl)propyl methacrylate and methanol. The same assumptions are made for read-across substance 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 half-lives of substances used for read-across in other areas are discussed below.

Hydrolysis of the read-across substance (trimethoxysilyl)methyl methacrylate (CAS Number: 54586-78-6)

Data for the substance (trimethoxysilyl)methyl methacrylate (CAS 54586-78-6) are read-across to the submission substance 3-trimethoxysilylpropyl methacrylate for appropriate endpoints (see Section 1.4 of the CSR). 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 CSR for each endpoint.

 

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

 

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

 

Hydrolysis of the read-across substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS Number: 121177-93-3)

Data for the substance [dimethoxy(methyl)silyl]methyl methacrylate (CAS 121177-93-9) are read-across to the submission substance 3-trimethoxysilylpropyl methacrylate for appropriate endpoints (see Section 1.4 of the CSR). 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 CSR for each endpoint.

 

For [dimethoxy(methyl)silyl]methyl methacrylate, hydrolysis half-lives at 20 - 25°C of 0.2 h at pH 4, 1.8 h at pH 7 and 0.04 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 0.6 hour 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 be considered that the half-life for the substance at pH 2 and 37.5°C is approximately 5 seconds.

 

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