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Environmental fate & pathways

Hydrolysis

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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 QMRF and QPRF documents
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.
Transformation products:
yes
No.:
#1
No.:
#2
Key result
pH:
4
DT50:
0.2 h
Remarks on result:
other: 20-25°C
Key result
pH:
5
DT50:
0.3 h
Remarks on result:
other: 20-25°C
Key result
pH:
7
DT50:
2.6 h
Remarks on result:
other: 20-25°C
Key result
pH:
9
DT50:
0.1 h
Remarks on result:
other: 20-25°C
Conclusions:
Hydrolysis half-life values between 20-25 °C of 0.2 h at pH 4, 0.3 h at pH 5, 2.6 h at pH 7 and 0.1 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: 0.2 h at pH 4, 0.3 h at pH 5, 2.6 h at pH 7, 0.1 h at pH 9, between 20-25 °C

Key value for chemical safety assessment

Half-life for hydrolysis:
2.6 h
at the temperature of:
25 °C

Additional information

Hydrolysis half-lives of 0.2 h at pH 4, 0.3 h at pH 5, 2.6 h at pH 7 and 0.1 h at pH 9, between 20-25 °C, were determined for the registration substance with the use of 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.


 


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 is therefore 0.002 hours (approximately 7 seconds) at 20 -25 °C. However, 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 therefore be considered that the half-life of the substance at pH 2 and 20-25 °C is approximately 5 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-(trimethoxysilyl)propane-1-thiol, the hydrolysis half-life at 37.5 ºC and pH 7 (relevant for lungs and blood) is approximately 1.0 hour. At 37.5 ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately 5 seconds.


 


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


 


The hydrolysis half-life of substances used for read-across in other areas are discussed below.


 


Hydrolysis of the read-across substance 3-(triethoxysilyl)propane-1-thiol (CAS No. 14814-09-6)


Data for the substance 3-(triethoxysilyl)propane-1-thiol (CAS No. 14814-09-6) are read-across to the submission substance 3-(trimethoxysilyl)propane-1-thiol for repeated dose toxicity oral and developmental toxicity endpoints. For acute toxicity oral and acute toxicity dermal endpoints, data for 3-(triethoxysilyl)propane-1-thiol has been used as supporting studies. The silanol hydrolysis product of the two substances is relevant to this read-across, as discussed in the appropriate section for each endpoint.


 


For 3-(triethoxysilyl)propane-1-thiol, hydrolysis half-lives of 0.6 h at pH 4, 0.6 h at pH 5, 19 h at pH 7 and 0.3 h at pH 9, between 20-25 °C, were obtained for the substance using a validated QSAR estimation method.


 


The half-lives at pH 2 and between 20-25 °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 0.006 h (approximately 22 seconds) at pH 2 and between 20 -25 °C. At pH 7 and 37.5 °C, the half-life is approximately 7 hours. At pH 2 and 37.5 °C, the half-life is 0.0022 h (8 seconds). However, 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 therefore be considered that the half-life of the substance at pH 2 and 37.5 °C is approximately 5 seconds.


 


The hydrolysis products are 3-(trihydroxysilyl)propanethiol and ethanol.