3-[tris(acetoxy)silyl]propyl methacrylate

Hydrolysis

Description of key information

Hydrolysis: Half-life <1 minute at 25°C and pH 4, 7 and 9 (semi-quantitative prediction in context of analogue read-across)

Key value for chemical safety assessment

Half-life for hydrolysis:

1 min

at the temperature of:

25 °C

Additional information

No hydrolysis study is available for the registered substance. However, reliable studies according to OECD 111 are available for three related triacetoxysilane substances. The acetate groups are fully hydrolysed within minutes at pH 4, 7 and 9 and 25°C. The measured half-lives at pH 4, 7 and 9 and 25ºC are all limit values.

Existing data for the hydrolysis of three related triacetoxysilane substances has been evaluated. The evaluation looks into the primary effects (type of bond to Si) and into the secondary effects (electronic and steric effect of R-groups). A QSAR model for alkoxysilanes as well as measured data for alkoxysilanes is used to extrapolate the effect of secondary factors for the half-life prediction for 3-[tris(acetoxy)silyl]propyl methacrylate.

The half-life of 3-[tris(acetoxy)silyl]propyl methacrylate at pH 7 and 25˚C is predicted to be very short (<1 min). No quantitative predictions have been performed for other pH values, though it can be stated that under these conditions the hydrolytic half-life is expected to be even shorter than that at pH 7. At higher temperatures (relevant for in vivo conditions), the hydrolytic half-life is expected to be even shorter than that at 25˚C.

The work is described in the expert report (PFA, 2014) attached to the Key Endpoint Study Record in Section 5.1.2.

It is not possible to attempt a quantitative prediction of rate or half-life, but there is no need to do so as the chemical safety assessment is not sensitive to this uncertainty within this range.

The hydrolysis of Si-O bonds is acid- or base catalysed. The above discussion investigates the likely half-life of the compound at pH 7 and 25°C. The rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered. Therefore, the hydrolysis half-life at pH4 and 25°C and at pH 9 and 25°C is expected to be <1 minute. The rate of reaction also increases with temperature. Therefore, at 37.5ºC and pH 7 (relevant for lungs and blood and in vitro and in vivo (intraperitoneal administration) assays), at 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), and at 37.5ºC and pH 5.5 (relevant for dermal exposure), the half-life for hydrolysis is expected to be <1 minute. No quantitative predictions or extrapolations are made for the substance at these pH values and temperature, because the predicted half-life for pH 7 and 25°C is already below 1 minute, and the accuracy of the prediction does not allow the half-life to be predicted with more accuracy than this.

Additional information is given in a supporting report (PFA 2013ac) attached in Section 13 of the REACH technical dossier. The hydrolysis products for the registered substance are 3-(trihydroxysilyl)propyl methacrylate and acetic acid.

The other reported studies (Dow Corning Corporation, 2002) was not designed to yield a quantitative measure of hydrolysis half-life at pH 4, 7 and 9. An in-vitro study of the test substance was conducted at pH 1.29 and 37°C. The relative molecular weight distribution (MWD) of the hydrolysis and condensation products was determined using a Gel Permeation Chromatography (GPC). Characterisation of both the hydrolysis and condensation products was determined using both Nuclear Magnetic Resonance (NMR) and Electrospray Ionisation Mass Spectrometry (ESI-MS). At pH 1.29 and 37°C, the test substance was observed to hydrolyse very rapidly and the hydrolysis products from the test substance underwent continuous, condensation reactions to produce higher molecular weight cyclic and linear siloxanes.

References:

PFA 2013ac   Peter Fisk Associates, Hydrolysis: Type 1b. Acetoxysilanes analogue group, PFA.300.005.003

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 2530-85-0

Data for the substance 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0) are read-across to the submission substance 3-[tris(acetoxy)silyl]propyl 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 3-trimethoxysilylpropyl methacrylate (CAS 2530-85-0), hydrolysis rates and half-lives have 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.

Additionally, hydrolysis half-lives at 20 - 25°C of 0.3 h at pH 4, 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, <1 h at pH 4 and <1 h at pH 9 and 25°C were determined in a preliminary study conducted in accordance with OECD 111 and in compliance with GLP.

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.

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 25°C using the predicted half-life at pH 4 is therefore 0.003 h (approximately 11 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-trimethoxysilylpropyl methacrylate the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 1.5 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 (0.1 - 1.5 hours).

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

Hydrolysis of the read-across substance triacetoxyethylsilane, CAS 17689-77-9

Data for the substance triacetoxyethylsilane (CAS 17689-77-9) are read-across to the submission substance 3-[tris(acetoxy)silyl]propyl 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 triacetoxyethylsilane (CAS 17689-77-9), the acetate groups are fully hydrolysed within minutes at pH 4, 7 and 9 and 25°C. The measured half-lives at pH 4, 7 and 9 and 25ºC are all limit values. 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. Therefore, the half-life at pH 2 (relevant for oral exposure) is <1 minute, and at pH 4, 5.5 (relevant for dermal exposure) and 9 is <1 minute. The available half-lives were all measured at 22-25ºC. Reaction rate increases with temperature and the half-lives at 37.5ºC (relevant for in vivo studies) are expected to be significantly faster.

The hydrolysis products in this case are ethylsilanetriol and acetic acid.