3-(triethoxysilyl)propyl methacrylate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

See attached QMRFs/QPRFs

Principles of method if other than guideline:

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details).

The model for hydrolysis at pH 7 has been developed for, and applies specifically to di- and tri-alkoxysilanes. It is a multiple linear regression based model with descriptors representing (i) steric effects of the alkoxy group, (ii) steric effects of the side-chain(s), and (iii) electronic effects of the side-chain(s).

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and apply specifically to organosilicon compounds. They are linear regression based models where the descriptor is the half-life at pH 7.

The results represent the hydrolysis half-life of the ethoxysilane groups rather than the whole substance.

Transformation products:

yes

No.:

#1

No.:

#2

Key result

pH:

4

DT50:

0.6 h

Remarks on result:

other: 20-25°C

Key result

pH:

5

DT50:

0.6 h

Remarks on result:

other: 20-25°C

Key result

pH:

7

DT50:

23.9 h

Remarks on result:

other: 20-25°C

Key result

pH:

9

DT50:

0.3 h

Remarks on result:

other: 20-25°C

Conclusions:

Hydrolysis half-life values at 20-25°C of 23.9 h at pH 7, 0.6 h at pH 4, 0.6 h at pH 5 and 0.3 h at pH 9 were obtained using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis half-life: 0.6 h at pH 4, 0.6 h at pH 5, 23.9 h at pH 7 and 0.3 h at pH 9 and 20-25°C (QSAR) (for reaction of ethoxysilane groups).

Key value for chemical safety assessment

Half-life for hydrolysis:

23.9 h

at the temperature of:

25 °C

Additional information

The registration substance 3-(triethoxysilyl)propyl methacrylate contains two types of hydrolysable groups: three ethoxysilane groups (which react to the corresponding silanols plus ethanol) 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 ethoxysilane groups:

Hydrolysis half-lives of 0.6 h at pH 4, 23.9 h at pH 7 and 0.3 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 0.006 h (approximately 22 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 3-(triethoxysilyl)propyl methacrylate, the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 8.8 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is 0.0022 hours (approximately 8 seconds). At pH 5.5 and 37.5°C (relevant for dermal exposure), the half-life is expected to be between that of pH 4 and pH 7 and 37.5°C i.e. 0.2 - 9 hours.

 

The hydrolysis products in this case are 3-(trihydroxysilyl)propyl methacrylate (1 mole) and ethanol (3 moles).

Hydrolysis of the methacrylate ester group:

Very limited evidence of the hydrolysis of the methacrylate ester group is available. The hydrolysis half-life of the epoxy group 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-(triethoxysilyl)propyl 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 exposure assessment at any relevant pH. Therefore, where the chemical safety assessment considers hydrolysis products, these are identified as 3-(trihydroxysilyl)propyl methacrylate and ethanol. 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-(triethoxysilyl)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. Also, predicted hydrolysis half-lives of 0.3 h at pH 4, 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, 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 second) 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 0.5 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 i.e. <0.01 - 0.5 h.

The hydrolysis products in this case are 3-(trihydroxysilyl)propyl methacrylate (1 mole) and methanol (3 moles).

Hydrolysis of the read-across substance 3-(trimethoxysilyl)methyl methacrylate CAS No. 54586-78-6)

Data for the substance, 3-(trimethoxysilyl)methyl methacrylate (CAS No. 54586-78-6) are read-across to the submission substance

3-(triethoxysilyl)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, 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 i.e. 0.1 - 1.5 hours.

The hydrolysis products in this case are 3-(trihydroxysilyl)methyl methacrylate (1 mole) and methanol (3 moles).