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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 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.
Transformation products:
yes
No.:
#1
No.:
#2
Key result
pH:
4
DT50:
0.7 h
Remarks on result:
other: 20-25°C
Key result
pH:
5
DT50:
0.7 h
Remarks on result:
other: 20-25°C
Key result
pH:
7
DT50:
30 h
Remarks on result:
other: 20-25°C
Key result
pH:
9
DT50:
0.4 h
Remarks on result:
other: 20-25°C
Conclusions:
Hydrolysis half-life values at 20-25°C of 0.7 h at pH 4, 30 h at pH 7 and 0.4 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 at 20-25°C approximately 30 h at pH 7, 0.7 h at pH 4, 0.4 h at pH 9 (QSAR)

Key value for chemical safety assessment

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

Additional information

Hydrolysis half-life values of 0.7 h at pH 4, 0.7 h at pH 5, approximately 30 h at pH 7 and 0.4 h at pH 9 and 20-25°C were obtained for the registered substance using validated QSAR estimation methods. The results are considered to be reliable and has been assigned as key study.

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 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. This is supported by studies for 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.

 

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 triethoxy(octyl)silane at pH 2 and 25°C is therefore 0.007 hours (25 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) x e(0.08.(T-X))

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

Thus, for triethoxy(octyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 11 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the hydrolysis half-life is 0.0026 h (9 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 submission substance at pH 2 and 37.5°C is approximately 5 seconds. At pH 5 and 37.5°C, the half-life is that between pH 4 and pH 7 i.e. 0.3-11 hours.

The hydrolysis products are octylsilanetriol and ethanol.

A supporting study for the read-across substance trimethoxy(methyl)silane (CAS 1185-55-3) is presented. In this study, the hydrolysis of trimethoxy(methyl)silane was investigated under conditions designed to mimic the rat stomach after dosing the substance in corn oil. The half-life for disappearance of trimethoxy(methyl)silane applied in corn oil to gastric simulation buffer was 33 minutes 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 trimethoxy(methyl)silane comes into contact with the aqueous layer and the rate determining step is the transfer of the trimethoxy(methyl)silane from the corn oil to the water. Combined recoveries of trimethoxy(methyl)silane and methanol (in mole equivalents of trimethoxy(methyl)silane; 3 moles methanol to 1 mole trimethoxy(methyl)silane assumed) were 87.5 to 104% and methanol content increased proportionally to the decrease in trimethoxy(methyl)silane. The study was conducted according to an appropriate test protocol and is considered reliable.

Trimethoxy(methyl)silane and triethoxy(octyl)silane are both trialkoxysilanes with an alkyl side-chain; the differences between the two substances are that the alkyl chain is C1 for trimethoxy(methyl)silane and C8 for triethoxy(octyl)silane and that the alkoxy group is methoxy for trimethoxy(methyl)silane and ethoxy for triethoxy(octyl)silane. Therefore, it is not intended to read-across the half-life for trimethoxy(methyl)silane to triethoxy(octyl)silane but to indicate the type of behaviour that might be observed for triethoxy(octyl)silane. Thus, in animal studies using corn oil as vehicle, triethoxy(octyl)silane could potentially hydrolyse more slowly than its predicted half-life at pH 2 and 37°C would suggest. This effect might be more pronounced for a substance with lower water solubility and higher log Kow.  It is uncertain to what extent the in vitro test results are relevant for conditions present in the rat stomach (for example composition of the applied gastric simulant was highly simplified, type/speed of mixing is expected to strongly influence phase partitioning).

The hydrolysis rates of the read-across substances used in other areas are discussed below:

Hydrolysis of the read-across substance triethoxy(2,4,4-trimethylpentyl)silane (CAS 35435-21-3)

Data for the substance triethoxy(2,4,4-trimethylpentyl)silane (CAS 35435-21-3) are read-across to the submission substance triethoxy(octyl)silane for the skin sensitisation endpoint. For the following endpoints, short-term toxicity to fish, short-term toxicity to aquatic invertebrates, long-term toxicity to aquatic invertebrates and toxicity to algae; the data for triethoxy(2,4,4 -trimethylpentyl)silane are used as supporting information only. The hydrolysis half-lives and silanol hydrolysis product of the two substances are relevant to this read-across as discussed in the appropriate section for each endpoint.

For triethoxy(2,4,4-trimethylpentyl)silane, hydrolysis half-lives at 20-25°C of 0.9 h at pH 4, 0.8 h at pH 5, 42.5 h at pH 7 and 0.5 h at pH 9 were determined 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 0.009 h (approximately 32 seconds) at pH 2 and 25°C, 0.003 h (approximately 11 seconds) at pH 2 and 37.5°C, and 16 h at pH 7 and 37.5°C. At 37.5°C and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life will be between half-lives at pH 5 and pH 7 (0.2 - 16 hours).

The hydrolysis products are (2,4,4-trimethylpentyl)silanetriol and ethanol.

Hydrolysis of the read-across substance trichloro(2,4,4-trimethylpentyl)silane (CAS 18379-25-4)

Supporting data for the substance trichloro(2,4,4-trimethylpentyl)silane (CAS 18379-25-4) are included for short-term toxicity to fish and long-term toxicity to aquatic invertebrates endpoints. The hydrolysis half-lives and silanol hydrolysis product of the two substances are relevant to this read-across as discussed in the appropriate section for each endpoint.

For trichloro(2,4,4-trimethylpentyl)silane, hydrolysis half-lives has been read-across from trichloro(methyl)silane (CAS 75-79-6 ). Hydrolysis half-lives of <1 minute at pH 4, <1 minute at pH 7 and <1 minute at pH 9 and 1.5°C were determined in accordance with OECD 111 (Dow Corning Corporation 2001). 

The hydrolysis products are (2,4,4-trimethylpentyl)silanetriol and hydrochloric acid.