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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 applies 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 at 20-25°C of 0.4 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, 2.6 h at pH 7, and 0.1 h at pH 9 and 20-25°C (QSAR)

Key value for chemical safety assessment

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

Additional information

Hydrolysis of 3-(trimethoxysilyl)propylamine (CAS Number: 13822-56-5)

The hydrolysis half-lives of 3-(trimethoxysilyl)propylamine have been predicted using a validated QSAR estimation method to be 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 and 20-25°C. The result is considered to be reliable and is selected as key study. In a secondary source to which reliability could not be assigned, a hydrolysis half-life of 17.8 minutes at 25°C was also reported; no information on pH was reported for the substance.

Hydrolysis reactions of alkoxysilanes can be catalysed by both acid and base. The rate of hydrolysis is slowest close to pH 7 and increases 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, 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+] = 10-4mol dm-3 and at pH 2 [H3O+] = 10-2 mol dm-3; therefore, kobs at 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 3-(trimethoxysilyl)propylamine at pH 2 and 20-25°C is therefore 0.002 hours (approximately 7 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 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) x e(0.08.(T-X))

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

Thus, for 3-(trimethoxysilyl)propylamine the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 1 hour. 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.

The final hydrolysis products are 3-aminopropylsilanetriol and methanol.

Hydrolysis of the read-across substance 3-aminopropyltriethoxysilane (CAS No: 919-30-2)

The hydrolysis data for 3-aminopropyltriethoxysilane(CAS No. 919-30-2) are now discussed. Data for this substance are read-across to the submission substance, 3-(trimethoxysilyl)propylamine 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-aminopropyltriethoxysilane, hydrolysis half-lives at 24.7°C of 0.8 h at pH 5, 8.5 h at pH 7 and 0.15 h at pH 9 were determined for the substance in accordance with OECD 111 (5.1.2.067, Dow Corning Corporation 2001). At pH 4, a predicted half-life of 0.4 h at 20-25°C was determined for the substance using 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 0.004 h (approximately 14 seconds) at pH 2 and 20-25°C, approximately 5 seconds at pH 2 and 37.5°C and approximately 3 hours at pH 7 and 37.5°C.

The final hydrolysis products are 3-aminopropylsilanetriol and ethanol.

Identity and formation/degradation rates of intermediate and final hydrolysis products

Trialkoxysilanes undergo hydrolysis in dilute aqueous solution via a series of pseudo first-order reactions as follows:

RSi(OR')3 (k1) ¿ RSi(OR')2(OH) (k2) ¿ RSi(OR')(OH)2 (k3) ¿ RSi(OH)3

where k1, k2 and k3 are the pseudo first order rate constants for the consecutive reactions. The half-lives quoted above refer to degradation of the parent substance.

Measured data for k1, k2 and k3 are available for 3-aminopropyltriethoxysilane (CAS 919-30-2) (Dow Corning Corporation 2001). Under all conditions, it was observed that k1 <k2 <k3, suggesting that the first hydrolysis step largely determines the time required to reach complete hydrolysis. The values obtained for the acid catalysed reaction are: k1= 23.1 M-1s-1, k2= 71.1 M-1s-1, k3= 132 M-1s-1. The values obtained for the base catalysed reaction are: k1= 125 M-1s-1, k2= 1130 M-1s-1, k3= not measured (as the reaction was too fast).

The concentration of each hydrolysis product has been plotted against time (expressed as number of half-lives for degradation of parent substance) for the acid catalysed reaction (see Figure 1 attached in Section 13). The parent compound dominates during the time span <1 half-life of the parent compound. The final hydrolysis product starts to dominate after approximately 1.5 half-lives of the parent compound have passed. After approximately 4 half-lives, the final hydrolysis product represents 90% of the compound present. Under basic or neutral conditions, the concentrations of the intermediate hydrolysis products reach lower maximums and begin to decrease more quickly because the ratios of k2 and k3 to k1 are greater than for the acid catalysed reaction. The rate constants used here are from Dow Corning Corporation (2001); the modelling has been done by the authors of this CSA.

The trends in k1, k2 and k3 observed for this substance are consistent with those observed for other trialkoxysilanes. The first step is the slowest and rate limiting factor. Each successive step is at least as fast as the previous one and often approximately twice as fast as the previous one.

Comparison of half-lives for the target (13822-56-5, 3-(trimethoxysilyl)propylamine) and source substances (919-30-2, 3-aminopropyltriethoxysilane)

The half-lives of the source and target substance at pHs and temperatures relevant for read-across are shown below.

pH

Temp (°C)

Target substance (13822-56-5)

Source substance (919-30-2)

Relevant for

2

37.5

5 s

5 s

Oral exposure

 7 37.5   1 h  3 h  Inhalation and dermal exposure, in vitro studies
 7 12   7 h  24 h  Ecotoxicity

 

For the source substance (CAS No. 919-30-2, 3-aminopropyltriethoxysilane), based on the values for k1, k2 and k3 discussed above, 90% conversion to the final hydrolysis product is predicted to take place within approximately 20 seconds at pH 2 and 37.5°C.

Data for k2 and k3 are not available for the target substance (CAS No: 13822-56-5, 3-aminopropyltrimethoxysilane). However, it is possible to conclude with confidence that hydrolysis of this substance is faster than that of the source substance. The speed of the hydrolysis of alkoxysilanes is driven by three major factors:

1)     Electronic effects of the side-chain – this value is identical for both substances as the side-chain propylamine is the same for both substances.

2)     Steric effects of the R-group – this value is identical for both substances as the side-chain propylamine is the same for both substances.

3)     Steric effects of the ether group.

The steric effect of the ether group means that substances with smaller groups have a shorter half-life than those with larger groups. The source substance (919-30-2) has three ethyl groups while the target substance (CAS No: 13822-56-5) has 3 methyl groups. The methyl group provides less steric hindrance at silicon than the ethyl group. As such the target compound will hydrolyse faster than the source compound under comparable conditions.

Therefore, at pH 2 and 37.5°C, both substances (CAS Nos: 13822-56-5 and 919-30-2) will be 90% hydrolysed to the same final silanol hydrolysis product within approximately 20 seconds.