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Environmental fate & pathways

Hydrolysis

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Endpoint:
hydrolysis
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The result was obtained by an appropriate predictive method.
Principles of method if other than guideline:
See attached QMRF and QPRF
Transformation products:
not specified
Key result
pH:
7
DT50:
5.5 h
Remarks on result:
other: approximately 20-25°C
pH:
4
DT50:
0.3 h
Remarks on result:
other: approximately 20-25°C
pH:
5
DT50:
0.3 h
Remarks on result:
other: approximately 20-25°C
pH:
9
DT50:
0.1 h
Remarks on result:
other: approximately 20-25°C
Conclusions:
A hydrolysis half-life of approximately 5.5 hours was obtained for the substance using an appropriate calculation method. The result is considered to be reliable pending the results of hydrolysis studies in simulated gastric media.
Endpoint:
hydrolysis
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
2017-01-12 to TBD
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Reason / purpose:
read-across source
Preliminary study:
The preliminary study was not required because methyltrimethoxysilane is known to be unstable in water.
Transformation products:
yes
No.:
#1
Details on hydrolysis and appearance of transformation product(s):
The decrease in concentration with time of methyltrimethoxysilane and the increase of concentration with time of methanol with time were followed (see Figure 1 and Figure 2). The anticipated reaction scheme is presented in the attachments section.
% Recovery:
>= 87.5 - <= 104
pH:
3
Temp.:
37 °C
Duration:
1 h
Remarks on result:
other: A molar recovery based on the quantity of methyltrimethoxysilane and molar equivalents of its hydrolysis product methanol (3 moles of methanol were assumed per mole of methyltrimethoxysilane) was between 87.5 and 104% at each time point
Key result
pH:
3
Temp.:
37 °C
Hydrolysis rate constant:
0.021 min-1
DT50:
33.3 min
Type:
(pseudo-)first order (= half-life)
Validity criteria fulfilled:
yes
Conclusions:
The hydrolysis of methyltrimethoxysilane was investigated under conditions designed to mimic the rat stomach after dosing the substance in corn oil. The half-life for disappearance of methyltrimethoxysilane applied in corn oil to gastric simulation buffer was 33 mins at pH 3 and 37°C and appears to be determined by phase transfer. The data suggest that, in the investigated system, hydrolysis occurs rapidly once methyltrimethoxysilane comes into contact with the aqueous layer and the rate determining step is the transfer of the methyltrimethoxysilane from the corn oil to the water. Combined recoveries of methyltrimethoxysilane and methanol (in mole equivalents of methyltrimethoxysilane; 3 moles methanol to 1 mole methyltrimethoxysilane assumed) were 87.5 to 104% and methanol content increased proportionally to the decrease in methyltrimethoxysilane. The study was conducted according to an appropriate test protocol and is considered reliable.

Description of key information

Hydrolysis half life: approximately 5.5 hours 20-25 °C

Key value for chemical safety assessment

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

Additional information

A hydrolysis half-life of approximately 5.5 hours at 20-25 °C was obtained for the substance using an appropriate calculation method. The result is considered to be reliable and has been assigned as the key result pending the results of hydrolysis studies in simulated gastric media.

A QSAR, which is currently being developed (Peter Fisk Associates 2012) predicts half-lives at 20-25°C of 0.3 h at pH 4 and 0.1 h at pH 9. 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.

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 extrem 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 from various organosilicon compounds, in which calculation of kH3O+and kOH-from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7 (Peter Fisk Associates (2012) and PFA, 2013).

Therefore, at low pH:

kobs≈kH3O+[H3O+]

At pH 4 [H3O+]=10-4mol dm-3and at pH 2 [H3O+]=10-2mol dm-3; therefore, kobsat pH 2 should be approximately 100 times greater than kobsat 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 triethoxy(methyl)silane at pH 2 is therefore 5 seconds. However, it is likely that factors such as diffusion become rate-determining when the half-life is less than 5-10 seconds.

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions and the half-lives at 37.5 ºC (relevant for in vivo studies) are expected to be faster than those at 20-25 °C. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT50(XºC) = DT50(T) x e(0.08*(T-X))

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

Thus, for triethoxy(methyl)silanethe hydrolysis half-life at 37.5 ºC and pH 7 (relevant for lungs and blood) is 2 hours. At 37.5ºC and pH 2 (relevant for the conditions in the stomach following oral exposure) is 5 seconds.

The initial hydrolysis products are methylsilanetriol and ethanol.

In another supporting study (CRL, 2017), the hydrolysis of methyltrimethoxysilane was investigated under conditions designed to mimic the rat stomach after dosing the substance in corn oil. The half-life for disappearance of methyltrimethoxysilane applied in corn oil to gastric simulation buffer was 33 mins at pH 3 and 37°C and appears to be determined by phase transfer. The data suggest that, in the investigated system, hydrolysis occurs rapidly once methyltrimethoxysilane comes into contact with the aqueous layer and the rate determining step is the transfer of the methyltrimethoxysilane from the corn oil to the water. Combined recoveries of methyltrimethoxysilane and methanol (in mole equivalents of methyltrimethoxysilane; 3 moles methanol to 1 mole methyltrimethoxysilane assumed) were 87.5 to 104% and methanol content increased proportionally to the decrease in methyltrimethoxysilane. The study was conducted according to an appropriate test protocol and is considered reliable.