Amino functional alkoxysilanes

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-10-13 to 2004-09-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes

Buffers:

The test system specified in the guideline requires distilled water, however, as the selected analytical method was 1H-NMR, it was necessary to use deuterated water to prepare the buffers. The relationship between pH and pD scales was established by Glasoe and Long. For solutions of comparable acidity of basicity the pH meter reading in D20 solution is 0.40 pH units lower than in H20 solution when calibrated against aqueous buffer standards. In this case: pD = pH meter reading + 0.40.
0.05 M buffer solutions were prepared to target pH 3.6, 6.6 and 8.6 by titration of formic acid (96%), sodium phosphate monobasic (99.0%) and boric acid (99.5%) solution, respectively, with sodium hydroxide (99.998%) solution. The formic acid, sodium phosphate monobasic, boric acid and sodium hydroxide were not deuterated.
Constant ionic strength was maintained for buffers by the addition of sodium chloride (99.999%). The ionic strength was not measured, but calculated based on buffer concentration/pH. Buffer solutions were made to known final volumes in polypropylene volumetric flasks with D2O. If necessary, final pH adjustments were made by dropwise addition of a concentrated sodium hydroxide or hydrochloric acid solution (prepared in D2O). The pH of each buffer solution was measured with a calibrated pH meter at the appropriate temperature and then converted to pD. Prior to use, the buffer solutions were sparged with argon gas for at least 5 min to exclude oxygen and sterilised through a 0.2µm filter.

Details on test conditions:

Kinetics experiments were conducted at the targeted pD 4, 7, and 9 at 25°C, pD 4 and 9 at 35°C and pD 4 and 9 at 10°C with buffer concentrations of 0.05M.
The experiment for pD 9 at 35°C was run in duplicate for repeatability purposes.
Buffers were thermostatted to ±0.1°C.
The test system consisted of buffered deuterated water (99.9 atom% D).
Due to the hydrolytically unstable nature of the test substance, the water miscible solvent ACN-d3 was used for application and distribution of the test substance in the test system. The acetonitrile was <1% (v/v) as allowed per the guideline.
Test systems: formic acid/NaOH for pD 4, sodium phosphate monobasic/NaOH for pD 7, and boric acid/NaOH for pD 9
Nominal initial concentration = 1x10-3 M (~150 mg/L). 
The hydrolysis reaction was initiated by adding an aliquot (95 µl) of the test substance solution (0.1 M MTMS in ACN-d3) to 10 ml of buffer (thermostatted to the appropriate temperature) using a gas tight volumetric syringe. The sample was immediately capped and inverted one time for mixing. Approximately 800 µl of the resulting sample was quickly transferred to an NMR tube and the 1H-NMR spectrum measured. The time between addition of the MTMS to the buffer and the first acquired spectrum was measured and recorded. To ensure the integrity of methyltrimethoxysilane, the test substance solution was analyzed by 1H-NMR before and after each set of hydrolysis kinetic experiments.

Number of replicates:

The experiment at pD 9 and 35°C was run in duplicate. The observed rate constants were 17.1420 and 18.3114 h-1 with a deviation of 3.3%. The deviation is slightly higher than the target 2.5% indicated in the OECD guideline because the NMR shims, resulting peak shape and resolution were better for replicate II than replicate I.

Statistical methods:

The hydrolysis of MTMS in dilute aqueous solution was observed to follow first-order kinetics for pD 7 and 9. The natural logarithm of the concentration (as peak intensity) was plotted as a function of reaction time. The observed rate constant, k, for the hydrolysis reaction is equal to the slope of a first-order regression line fitted to the data. The half-life of the hydrolysis reaction was calculated from the estimated rate constant according to the following equation: t1/2 = ln 2/k, where k is the reaction rate constant and t1/2 is the half-life of the test substance. Descriptive statistics such as average, average deviation, percent, and linear regression analysis were also performed.

Preliminary study:

The preliminary test at 50°C was not conducted since MTMS is considered hydrolytically unstable (t1/2 < 1 year).

Transformation products:

yes

No.:

#1

No.:

#2

Details on hydrolysis and appearance of transformation product(s):

Degradation products: Methylsilanetriol and methanol (CAS No. 67-56-1)
The hydrolysis product, methanol, was observed in  this study.  Based on the chemical structure of MTMS, this hydrolysis is expected to produce 3 moles of methanol and 1 mole of methylsilanetriol  (SEHSC (2008) Communication from T Hill, Scientific Programs Manager 
Silicones Environmental, Health and Safety Council.)

Key result

pH:

4

Temp.:

10 °C

DT50:

< 0.034 h

Remarks on result:

other: <2 min; hydrolysis too rapid to determine rate constant

Key result

pH:

4

Temp.:

25 °C

DT50:

0 - < 0.033 h

Remarks on result:

other: <2 min; hydrolysis too rapid to determine rate constant

Key result

pH:

4

Temp.:

35 °C

DT50:

< 0.021 h

Remarks on result:

other: <2 min; hydrolysis too rapid to determine rate constant

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.32 h-1

DT50:

2.2 h

Type:

(pseudo-)first order (= half-life)

Key result

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

1.86 h-1

DT50:

0.37 h

Type:

(pseudo-)first order (= half-life)

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

6.04 h-1

DT50:

0.11 h

Type:

(pseudo-)first order (= half-life)

Key result

pH:

9

Temp.:

35 °C

Hydrolysis rate constant:

17.7 h-1

DT50:

0.039 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Average rate constant (rep I 17.1 h-1, rep II 18.3 h-1)

Conclusions:

Hydrolysis half-lifes at 25°C of <0.033 h, 2.2 h and 0.11 h were determined at pH 4, 7 and 9, respectively, in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Executive summary:

MTMS hydrolysis was followed by measuring its disappearance as a function of time by 1H-NMR spectroscopy. The hydrolysis was observed to follow pesudo-first order kinetics for pD 7 and 9, was pH dependent (faster at pH 4 and 9 than pH 7), and accelerated at higher temperature. The hydrolysis of MTMS for pD 4 was so rapid that insufficient data was obtained to determine the hydrolysis rate, however, the data were adequate for estimating the upper limit of t_1/2.

According to the definition put forth in the test guidelines, the test substance was observed to be hydrolytically unstable (t1/2 <1 year) over a range of environmentally relevant pD conditions at 10.0, 25.0, and 35.0°C.

Reference 2

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

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.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was not conducted in compliance with GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Individual kinetic experiments were conducted in one of two modes, depending on the expected half-life of the parent substance. The first mode was used for half-life < ca. 45 min (pH <5 or >8) and involved a separate reaction aliquot for each unique reaction time to be sampled. Immediately prior to analysis of a particular sample, the hydrolysis reaction was quenched by rapid adjustment to pH 6.7±0.5 by addition of acid or base. The final pH of a subset of samples was verified.

The second mode was used for pH 5-8 and involved up to four staggered reaction solutions. The separate reactions were repeatedly sampled in alternating fashion over several hours to collect hydrolysis data spanning approximately 3 half-lives of the parent substance.

On average, data were collected at 12 discrete times for each kinetic experiment.

Buffers:

Buffer solutions of known pH and concentration were prepared by titration of 1M glacial acetic acid or tris(hydroxymethyl)-aminomethane (99.9%) solution with 1M sodium hydroxide (99.998%) or hydrochloric acid solution (37 wt%), respectively. A constant ionic strength of 0.30 M was maintained by addition of an appropriate volume of 2M sodium chloride solution. Buffer solutions were made to known final volume in polypropylene volumetric flasks with deionized water (>18 MΩ cm). If necessary, final pH adjustments were made by dropwise addition of sodium hydroxide or hydrochloric acid using a calibrated pH meter. Prior to use all buffer solutions were sparged with argon for at least 15 min. As the test material was capable of altering solution pH through the basic primary amine, the pH reported for a given experiment was taken as that which was measured following silane addition.

Details on test conditions:

5*10-2 M stock solutions of the test material in acetonitrile were prepared in a nitrogen-purged glove bag and stored in 22 ml plastic vials having septum lined open-top caps. When not in use, the vials were stored in a secondary airtight container filled with Drierite.
Kinetic experiments were conducted over the pH range 4.7-9.0 with buffer concentrations varying from 20 to 200 mM for acetic acid/sodium acetate and 20 to 300 mM for Tris-HCl/Tris. As the hydrolysis reactions were expected to show general base catalysis, buffer concentrations were selected to give particular concentrations of the conjugate base over the range of pH covered by each buffer.
Experiments were conducted at 9.6 to 34.8°C, thermostatted to ±0.1°C.
The starting concentration was not varied as previous studies have demonstrated that the reaction rate in dilute aqueous solution is first order in silane concentration.
The reactions employed initial silane concentrations of 5*10-4 M (1 part silane stock solution + 100 parts buffer solution).

Statistical methods:

The changes in peak area associated with each of the four components of the reaction mixture (parent, intermediates and product) over time contain kinetic information pertaining to the rates of the three consecutive hydrolysis reactions. Unconstrained nonlinear regression analysis was used to obtain estimates for the rate constants k1, k2 and k3 by simultaneously fitting the dataset to a kinetic model based on pseudo-first order kinetics for each reaction. A parameter was added to account for the varying sensitivity of the instrument to each component. The initial silane concentration was treated as a fixed parameter.

The analysis was performed using Origin 6.0 data analysis software, which employs the Levenburg-Marquardt minimization algorithm. The software varied the software parameters iteratively. The tolerance was set at 0.01%. Convergence was typically reached in 3-4 iterations, although in one case 8 interations were required.

Preliminary study:

No preliminary study was carried out.

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

No.:

#4

Details on hydrolysis and appearance of transformation product(s):

Trialkoxysilanes undergo hydrolysis in dilute aqueous solution via a series of consecutive pseudo first order reactions:
RSi(OR')3 → RSi(OR')2(OH) → RSi(OR')(OH)2 → RSi(OH)3
One mole of alcohol (in this case ethanol) is released at each hydrolysis step.

The observed changes over time in the chromatographic peaks areas, together with the assumption that the components elute in order of decreasing hydroxyl substitution (polarity), served as a basis for the peak assignments.

The signal associated with the parent silane followed a simple exponential decrease over time. The peak corresponding to the first hydrolysis product (transformation product #1) appeared early in the reaction, closely followed by the concurrent appearance of the second intermediate (transformation product #2) and the silanetriol product (transformation product #3). The peaks of the intermediate products reached maxima part way through the hydrolysis process, followed by a gradual decrease that continued until completed hydrolysis was reached.

Over the pH range investigated, the intermediate silanol products (the mono- and di-ol) were observed to hydrolyze more rapidly than the original tri-alkoxysilane.  Consequently, these breakdown products can be considered transient. 

Key result

pH:

5

Temp.:

24.7 °C

DT50:

0.8 h

Type:

(pseudo-)first order (= half-life)

Key result

pH:

7

Temp.:

24.7 °C

DT50:

8.5 h

Type:

(pseudo-)first order (= half-life)

Key result

pH:

9

Temp.:

24.7 °C

DT50:

0.15 h

Type:

(pseudo-)first order (= half-life)

Details on results:

The minimum hydrolysis rate at 24.7°C occurred at pH 6.6, with a half-life of 620 min (10.3 h). Extrapolating to 0°C, the maximum possible half-life was estimated as 150 h at pH 6.9. Under all conditions, it was observed that k1
Non-linear regression analysis was applied to the data describing changes in component peak area as a function of reaction time to obtain estimates of the consecutive hydrolysis rate constants. Very good agreement between experimental data and fitted curves was observed for all four components. Appropriate statistical tests indicated that the data adhere to the chosen kinetic model.

Nominal initial concentration = 5x10^-4 M (~110 mg/L). The concentration was not directly measured; rate constants were extracted  from changes in analytical response for each component.

Table 1.  Observed rate constants for hydrolysis reactions of APTES

Run	pH	T / °C	[buffer], mM	k1* 10^4. s^-1(uncertainty)	k2* 10^4. s^-1 (uncertainty)	k3* 10^4. s^-1 (uncertainty)
15	4.77	25	18.3	3.99 (0.18)	12.7 (3.1)	31.3 (12.7)
12	4.70	25	183	6.76 (0.19)	27.7 (5.2)	70.9 (49.7)
8	4.94	25	28.5	3.24 (0.18)	10.8 (3.3)	18.7 (8.1)
5	4.97	25	142	3.38 (0.09)	13.9 (2.2)	39.7 (13.4)
11	5.82	25	21.8	0.434 (0.017)	1.67 (0.31)	2.95 (0.78)
13	5.69	25	109	0.737 (0.020)	2.63 (0.38)	12.5 (5.4)
2	7.07	25	88.1	0.240 (0.003)	1.67 (0.06)	-
14	7.01	25	317	0.276 (0.013)	1.49 (0.53)	-
6	8.00	25	53.3	1.45 (0.05)	13.1 (1.5)	-
7	7.97	25	266	1.53 (0.04)	15.4 (1.4)	-
10	8.69	25	133	6.53 (0.26)	60.1 (6.9)	-
9	9.08	25	23.3	15.4 (0.7)	78.7 (7.6)	-
20	9.04	25	23.3	13.6 (0.6)	89.9 (8.5)	-
16	4.77	9.58	18.3	1.87 (0.11)	5.23 (1.39)	14.4 (7.2)
15	4.77	24.70	18.3	3.99 (0.18)	12.7 (3.1)	31.1 (12.7)
19	4.73	34.80	18.3	7.75 (0.21)	22.6 (2.3)	60.9 (11.3)
17	8.97	9.68	23.3	2.61 (0.14)	15.9 (3.0)	-
20	9.04	24.75	23.3	13.6 (0.6)	89.9 (8.5)	-
18	9.05	34.75	23.3	38.7 (1.9)	239 (27)	-

Effect of pH on the hydrolysis kinetics

For an acid-base catalysed hydrolysis reaction in aqueous buffered solution, the measured rate constant kobs is described by the general equation:

k_obs = k₀+ k_H3O+[H₃O⁺] + k_OH-[OH^-] + k_a[acid] + k_b[base]

where k₀ refers to the spontaneous reaction with water and the latter two terms provide for possible catalysis by the conjugate acid and base of the particular buffer. k_H3O+ and k_OH- are the acid and base catalysed rate constants.

In order to understand the effect of pH on the stepwise hydrolysis of the test substance, a series of kinetic runs were conducted over a range of pH using acetate and Tris buffers of varying concentration. Varying the concentration of the buffer allows its catalytic effect to be elucidated; this is mainly interesting in terms of it impact on the investigation of pH effects. Non-linear regression analysis was used (as discussed in the methods section) to determine values of k₁ and k₂ and, if possible, k₃ for each experiment corresponding to a particular pH and buffer composition. The results are shown in Table 1 above.

Multiple linear regression analysis was then used to model the effect of hydronium or hydroxide ion concentratoin and buffer concentration on the observed rates of hydrolysis. The results are shown in Table 2 (for pH 4.7 -5.9, dominated by hydronium ion catalysis) and Table 3 (for pH , dominated by hydroxide ion catalysis).

Table 2: Results of multiple linear regression analysis of APTES kinetic experiments in the pH range 4.7 -5.8 at 24.7°C

Variable (units)	k1 (significance, P)	k2 (significance, P)	k3 (significance, P)
[H3O^+] (M^-1 s^-1)	23.1 (0.0012)	71.1 (0.0020)	132 (0.0143)
[HOAc] (M^-1 s-^1)	2.43E-03 (0.0124)	1.59E-02 (0.0025)	5.19E-02 (0.0035)
Intercept (s^-1)	5.5E-06 (0.7815)	8.7E-06 (0.9054)	2.4E-04 (0.4051)
Adjusted r^2	0.9891	0.9909	0.9812

Table 3: Results of multiple linear regression analysis of APTES kinetic experiments in the pH range 7.0 -9.0 at 24.7°C

Variable (units)	k1 (significance, P)	k2 ^a(significance, P)	k3 ^b (significance, P)
[OH^-] (M^-1s^-1)	125 (0.0000)	1130 (0.0005)	-
[Tris] (M^-1s-^1)	3.24E-04 (0.0051)	4.75E-03 (0.0547)	-
Intercept (s^-1)	7.8E-06 (0.0702)	5.9E-06 (0.9188)	-
Adjusted r^2	0.9999	0.9991	-

^a pH 9.0 data not included in the model for k₂ due to poor initial fit with a large standardized residual for this observation.

^b Final hydrolysis step was too rapid to measure quantitatively

It can be seen from the above tables that [H₃O⁺] and [OH^-] are very significant (P<0.01) in all cases. The coefficients are the second order catalytic constants, k_H3O+ and k_OH-, for the first, second and (for k_H3O+) third hydrolysis steps. At the higher pH, the third hydrolysis step was too rapid to measure quantitatively in all cases. The adjusted r² for the final model is >0.98 in all cases.

The buffer concentrations, described by [HOAc] and [Tris] were found to be significant, indicating that buffer catalysis is occuring.

k_H3O+ and k_OH- both increase for successive hydrolysis steps, with k_OH- increasing to a much greater extent.

A statistically significant intercept term (P<0.1) was obtained for the intercept of k₁ in the higher pH experiments. This represents k₀ for the first hydrolysis step.

There was good agreement between measure values of k₁, k₂ and k₃ and those predicted based on the linear regression analyses from the two catalytic regimes. This indicates that the model results accurately represent the experimental data and that the chosen variables account for most of the variance in the data.

Effect of temperature on the hydrolysis kinetics

To determine the effect of temperature on the rate of hydrolysis of the parent silane and the intermediate hydrolysis products, additional kinetic runs were made at 10 and 35°C and pH 4.7 and 9.0, using the lowest buffer concentrations from the respective 25°C runs. Under these conditions, the change in the observed rate constant with temperature should relate predominantly to the specific acid and base catalysed mechanisms. The results are shown in Table 1 above. These rate constants were used to construct a series of three-point Arrhenius plots from which pre-exponential factors (A) and activation energies (Ea) were estimated for the specific acid and base catalysed reactions. The results are given in Table 4 below.

Table 4: Arrhenius parameters for the Hydronium and Hydroxide Ion Catalyzed Hydrolysis Reactions of APTES

	A, s^-1	Ea, kJ/mol	r^2
k1 H3O+	5.00E03	40.3	0.9900
k2 H3O+	2.80E04	41.8	0.9997
k3 H3O+	4.72E04	40.7	0.9901
k1 OH-	6.09E10	77.8	0.9999
k2 OH-	5.00E11	78.5	0.9996
k3 OH-	-	-	-

For each plot r² was found to exceed 0.99, suggesting that a single dominant reaction pathway (ie specific acid or specific base catalysis) is being observed at each extreme of pH. There is not enough data to draw conclusions on the significance of the variation in E_a among the stepwise reactions, although they do appear to be very similar. However, it is clear that the activation energies are approximately a factor of 2 larger for the hydroxide catalysed reaction.

The Arrhenius parameters can be used with the previously discussed catalytic constants to predict t_1/2 for the disappearance of the test substance as a function of pH and temperature at zero buffer concentration. This is shown in Figure 5 (attached) for the three temperatures examined during the study. It should be noted that k₀ is only included in the 25°C curve as the temperature dependence of this reaction pathway has not been determined. Therefore, the other curves represent conservative estimates of half-life particularly in the pH region where the rate is near minimum.

Conclusions:

A hydrolysis half life for disappearance of parent substance of 8.5 h at pH 7 and 24.7°C was determined in a reliable study conducted according to an appropriate test protocol but not conducted according to GLP. The subsequent hydrolysis steps and the temperature and pH dependence of the hydrolysis kinetics were also investigated.

Executive summary:

The kinetics of the hydrolysis reactions of 3-aminopropyl-triethoxysilane in dilute aqueous solution were characterized over a range of environmentally relevant pH and temperature. The results are consistent with a series of consecutive pseudo-first order reactions having an increasing rate for each subsequent hydrolysis step (k₁<k₂<k₃). Reaction rates are strongly influenced by pH, with catalysis by hydroxide ion being 5 times more effective than hydronium ion at promoting hydrolysis of the parent trialkoxysilane; this discrepancy increases for the subsequent reactions leading to formation of the silanetriol. In addition, the contribution of the solvent catalyzed reaction, k₀, is significant to the overall rate of hydrolysis of ATPES extrapolated to zero buffer concentration. Given that the first hydrolysis reaction, k₁, is rate limiting and using 10 half-lives as the definition of "complete", this study indicates that the trialkoxysilane will be exhaustively hydrolyzed to the silanetriol in ≤4.5 days at 25°C.

Reference 4

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, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

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

No.:

#3

No.:

#4

No.:

#5

No.:

#6

Key result

pH:

4

DT50:

0.1 h

Remarks on result:

other: 20 - 25°C

Remarks:

Constituents A weighted average

Key result

pH:

7

DT50:

2 h

Remarks on result:

other: 20 - 25°C

Remarks:

Constituents A weighted average

Key result

pH:

9

DT50:

0.03 h

Remarks on result:

other: 20 - 25°C

Remarks:

Constituents A weighted average

Key result

pH:

4

DT50:

0.3 h

Remarks on result:

other: 20 - 25°C

Remarks:

Constituents B weighted average

Key result

pH:

7

DT50:

4.8 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents B weighted average

Key result

pH:

9

DT50:

0.1 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents B weighted average

Key result

pH:

4

DT50:

0.4 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents C weighted average

Key result

pH:

7

DT50:

10.8 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents C weighted average

Key result

pH:

9

DT50:

0.2 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents C weighted average

Key result

pH:

4

DT50:

0.3 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents D weighted average

Key result

pH:

7

DT50:

5.9 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents D weighted average °C

Key result

pH:

9

DT50:

0.1 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents D weighted average °C

Key result

pH:

4

DT50:

0.3 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents E weighted average

Key result

pH:

7

DT50:

5.9 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents E weighted average

Key result

pH:

9

DT50:

0.1 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents E weighted average

Key result

pH:

4

DT50:

0.3 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents F weighted average

Key result

pH:

7

DT50:

5.9 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents F weighted average

Key result

pH:

9

DT50:

0.1 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents F weighted average

Key result

pH:

4

DT50:

0.4 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents G weighted average

Key result

pH:

7

DT50:

11.6 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents G weighted average

Key result

pH:

9

DT50:

0.2 h

Remarks on result:

other: 20-25°C

Remarks:

Constituents G weighted average

The half-lives for the constituents of the substance are shown below. The half-lives represent loss of parent substance.

Constituent	Constituent SMILES (canonical)	Result: t1/2 (h) at pH 7	Result: t1/2 (h) at pH 4	Result: t1/2 (h) at pH 5	Result: t1/2 (h) at pH 9
A1	CO[Si](OC)(OC)C	2.2*	<0.033*		0.11*
A2	CCO[Si](OC)(OC)C	1.6	0.1	0.2	0.03
A3	CCO[Si](OCC)(OC)C	3.1	0.2	0.3	0.1
A4	CCO[Si](OCC)(OCC)C	5.9	0.3	0.4	0.1
Constituents A weighted average		2.0	0.1	0.2	0.03
B1	NCCC[Si](OC)(OC)OC	2.6	0.2	0.3	0.1
B2	NCCC[Si](OCC)(OC)OC	5.5	0.3	0.3	0.1
B3	NCCC[Si](OCC)(OCC)OC	8.5**		0.8**	0.15**
B4	NCCC[Si](OCC)(OCC)OCC	8.5*		0.8*	0.15*
Constituents B weighted average		4.8	0.3	0.6	0.1
C1	CO[Si](CCCOCC1CNCCC[Si](O1)(OC)OC)(OC)OC	7.9	0.4	0.4	0.1
C2	CCO[Si]1(OC)CCCNCC(O1)COCCC[Si](OC)(OC)OC	8.5	0.4	0.4	0.1
C3	CCO[Si]1(CCCNCC(O1)COCCC[Si](OC)(OC)OC)OCC	9.2	0.4	0.4	0.2
C4	CCO[Si](CCCOCC1CNCCC[Si](O1)(OCC)OCC)(OC)OC	18.0	0.5	0.6	0.3
C5	CCO[Si](OCC)(CCCOCC1CNCCC[Si](O1)(OCC)OCC)OC	35.0	0.8	0.7	0.5
Constituents C weighted average		10.8	0.4	0.4	0.2
D1	CO[Si](OC(COCCC[Si](OC)(OC)OC)CNCCC[Si](OC)(OC)OC)(OC)C	5.9	0.3	0.4	0.1
D2	CCO[Si](CCCNCC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)(OC)OC	5.9	0.3	0.4	0.1
D3	CCO[Si](OCC)(CCCNCC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)OC	5.9	0.3	0.4	0.1
D4	CCO[Si](OCC)(OCC)CCCNCC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC	5.9	0.3	0.4	0.1
D5	CCO[Si](CCCOCC(O[Si](OC)(OC)C)CNCCC[Si](OCC)(OCC)OCC)(OC)OC	5.9	0.3	0.4	0.1
D6	CCO[Si](OCC)(CCCOCC(O[Si](OC)(OC)C)CNCCC[Si](OCC)(OCC)OCC)OC	5.9	0.3	0.4	0.1
Constituents D weighted average		5.9	0.3	0.4	0.1
E1	CCO[Si](CCCN(CC1COCCC[Si](O1)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)(OC)OC	5.9	0.3	0.4	0.1
E2	CCO[Si](OCC)(CCCN(CC1COCCC[Si](O1)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)OC	5.9	0.3	0.4	0.1
E3	CCO[Si](OCC)(OCC)CCCN(CC1COCCC[Si](O1)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC	5.9	0.3	0.4	0.1
E4	CCO[Si](OCC)(OCC)CCCN(CC1COCCC[Si](O1)(OC)OCC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC	5.9	0.3	0.4	0.1
Constituents E weighted average		5.9	0.3	0.4	0.1
F1	CO[Si](CCCN(CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)(OC)OC	5.9	0.3	0.4	0.1
F2	CCO[Si](CCCN(CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)(OC)OC	5.9	0.3	0.4	0.1
F3	CCO[Si](OCC)(CCCN(CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)OC	5.9	0.3	0.4	0.1
F4	CCO[Si](OCC)(OCC)CCCN(CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC	5.9	0.3	0.4	0.1
F5	CCO[Si](OCC)(OCC)CCCN(CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OCC)(OC)OC	5.9	0.3	0.4	0.1
F6	CCO[Si](OCC)(OCC)CCCN(CC(O[Si](OC)(OC)C)COCCC[Si](OC)(OC)OC)CC(O[Si](OC)(OC)C)COCCC[Si](OCC)(OCC)OC	5.9	0.3	0.4	0.1
Constituents F weighted average		5.9	0.3	0.4	0.1
G1	CO[Si](O[Si](OC)(OC)C)(OC)C	11.6	0.4	0.5	0.2
G2	CCO[Si](O[Si](OC)(OC)C)(OC)C	11.6	0.4	0.5	0.2
Constituents G weighted average		11.6	0.4	0.5	0.2

*Measured hydrolysis half-lives

**Read-across from Constituent B4

Conclusions:

Hydrolysis half-lives of the constituents of the subsmission substance using validated calculation methods. Some constituents are outside the domain of the prediction and the half-lives are likely to be overestimated.

Description of key information

Hydrolysis half-lives

Constituents A: 0.1 h at pH 4, 2.0 h at pH 7 and 0.1 h at pH 9 and 20-25°C

 

Constituents B: 0.3 h at pH 4, 4.8 h at pH 7, and 0.1 h at pH 9 and 20-25°C

 

Constituents C: 0.4 h at pH 4, 10.8 h at pH 7, and 0.2 h at pH 9 and 20-25°C

 

Constituents D: 0.3 h at pH 4, 5.9 h at pH 7, and 0.1 h at pH 9 and 20-25°C

 

Constituents E: 0.3 h at pH 4, 5.9 h at pH 7, and 0.1 h at pH 9 and 20-25°C

 

Constituents F: 0.3 h at pH 4, 5.9 h at pH 7, and 0.1 h at pH 9 and 20-25°C

 

Constituents G: 0.4 h at pH 4, 11.6 h at pH 7, and 0.2 h at pH 9 and 20-25°C

Additional information

The registration substance is UVCB substance containing many constituents with a variety of structures and physicochemical properties (for example, water solubility ranging from 0.31 to 570000 mg/L); therefore, testing for hydrolysis rate would be technically difficult due to the requirement for a suitably sensitive analytical method. The calculated hydrolysis half-lives refer to the first alkoxysilane group to hydrolyse; once the first group has undergone hydrolysis, the subsequent hydrolysis steps are assumed to be faster. The constituents of the substance are methoxy-, ethoxy- or mixed methoxy-/ethoxy-silanes. The alkoxysilane groups are susceptible to hydrolysis, producing silanols and ethanol and/or methanol.

Under dilute conditions relevant for the environment, the hydrolysis of each constituent can be considered separately. The hydrolysis half-lives of each constituent are reported in the table below and the hydrolysis reactions are illustrated in the attached document in Section 13 'EC (701-410-9) Composition and hydrolysis 20211216'. Where there is more than one constituent within a Block, the weighted average half-lives are reported in the table below.

 

The half-lives at pH 7 and 20-25°C for each constituent have been calculated and/or measured as reported in the table below. The calculated hydrolysis half-lives refer to the first alkoxysilane group to hydrolyse; once the first group has undergone hydrolysis, the subsequent hydrolysis steps are expected to be faster. For some constituents, a measured hydrolysis rate is available and this is quoted in the table below instead of the predicted results.

Some constituents are outside the descriptor and/or structure domain of the QSAR prediction, therefore, there is greater uncertainty in the predicted values. In addition, alkoxysilanes containing amine groups hydrolyse more quickly than predicted due to an intramolecular catalysis mechanism. For example constituent B4 has a predicted half-life at pH 7 and 20-25°C of 21 h and a reliable measured value of 8.5 h. Therefore, the half-lives are considered to represent an upper-bound for the true hydrolysis rates. Uncertainty in the predicted values for constituents C-G is considered in the chemical safety assessment by performing environmental exposure assessment and risk characterisation on the parent constituents as well as the hydrolysis product assessment entities.

The half-lives at 20-25°C and pH 4 and pH 9 have also been predicted using a validated QSAR method, which uses the hydrolysis rate at pH 7 as input. 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.

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

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.

However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. Therefore, when a half-life of <5 seconds is calculated, the half-life is quoted as 5 seconds (0.001 h).

The half-lives at pH 2 (relevant for conditions in the stomach following oral exposure), pH 4, pH 5, pH 5.5 (relevant for lungs and blood), pH 7 and pH 9 are summarised in the table below.

Table 4.1.2 Hydrolysis half-lives in hours for the constituents of the registration substance

	Temp	20-25°C	20-25°C	20-25°C	20-25°C	20-25°C	37.5°C	37.5°C	37.5°C
Constituent	Hydrolysis product^d	pH 2	pH 4	pH 5	pH 7	pH 9	pH 2	pH 5.5	pH 7
Constituent A1	Silanol HP-X	0.001	<0.033^a	0.2	2.2^a	0.11^a	0.001	0.07 – 0.81	0.81
Constituent A2	Silanol HP-X	0.001	0.1	0.2	1.6	0.03	0.001	0.07 – 0.59	0.59
Constituent A3	Silanol HP-X	0.002	0.2	0.3	3.1	0.1	0.001	0.1 – 1.1	1.1
Constituent A4	Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.1-2.2	2.2
Weighted average Constituents A		0.001	0.1	0.2	2.0	0.1	0.001		0.7
Constituent B1	Silanol HP-Z	0.002	0.2	0.3	2.6	0.1	0.001	0.1-0.96	0.96
Constituent B2	Silanol HP-Z	0.003	0.3	0.3	5.5	0.1	0.001	0.1-2.0	2.0
Constituent B3	Silanol HP-Z	0.004	0.4	0.8^b	8.5^b	0.15^b	0.001	0.29-3.1	3.1
Constituent B4	Silanol HP-Z	0.004	0.4	0.8^c	8.5^c	0.15^c	0.001	0.29-3.1	3.1
Weighted average Constituents B		0.003	0.3	0.4	4.8	0.1	0.001		1.8
Constituent C1	Silanol HP-Y	0.004	0.4	0.4	7.9	0.1	0.001	0.14-2.8	2.8
Constituent C2	Silanol HP-Y	0.004	0.4	0.4	8.5	0.1	0.001	0.14-3.1	3.1
Constituent C3	Silanol HP-Y	0.004	0.4	0.4	9.2	0.2	0.001	0.14-3.3	3.3
Constituent C4	Silanol HP-Y	0.005	0.5	0.6	18.0	0.3	0.002	0.22-6.5	6.5
Constituent C5	Silanol HP-Y	0.008	0.8	0.7	35.0	0.5	0.003	0.25-13	13.0
Weighted average Constituents C		0.004	0.4	0.4	10.8	0.2	0.001		3.9
Constituent D1	Silanol HP-Y + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent D2	Silanol HP-Y + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent D3	Silanol HP-Y + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent D4	Silanol HP-Y + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent D5	Silanol HP-Y + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent D6	Silanol HP-Y + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Weighted average Constituents D		0.003	0.3	0.4	5.9	0.1	0.001		2.1
Constituent E1	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent E2	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent E3	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent E4	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Weighted average Constituents E		0.003	0.3	0.4	5.9	0.1	0.001		2.1
Constituent F1	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent F2	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent F3	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent F4	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent F5	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Constituent F6	Silanol HP-W + Silanol HP-X	0.003	0.3	0.4	5.9	0.1	0.001	0.14-2.1	2.1
Weighted average Constituents F		0.003	0.3	0.4	5.9	0.1	0.001		2.1
Constituent G1	Silanol HP-X	0.004	0.4	0.5	11.6	0.2	0.001	0.18-4.2	4.2
Constituent G2	Silanol HP-X	0.004	0.4	0.5	11.6	0.2	0.001	0.18-4.2	4.2
Weighted average Constituents G		0.004	0.4	0.5	11.6	0.2	0.001		4.2

^aHydrolysis half-lives at 25°C of <0.033 h at pH 4, 2.2 h at pH 7 and 0.11 h at pH 9 were obtained in a reliable study according to OECD 111 (SEHSC 2004).

^bThe predicted half-life at pH 7 and 20-25°C is 11 h. This mixed methoxy-/ethoxy-silane is expected to hydrolyse faster than the equivalent triethoxysilane (constituent B4; measured half-life at pH 7 and 24.7°C 8.5 h, predicted half-life 21 h). Therefore, as a worst-case, the half-life of 8.5 h is read-across from constituent B4.

^cHydrolysis 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 obtained in a reliable study according to OECD 111 (Dow Corning Corporation 2001).

^dSilanol hydrolysis product(s) with methanol/ethanol

Where:

Silanol HP-X = Methylsilanetriol

Silanol HP-Y = Disilyl(alkylamine)-heptol

Silanol HP-Z = (3-Aminopropyl)silanetriol

Silanol HP-W = Trisilyl(alkylamine)-undecol

The hydrolysis half-lives of substances/constituents used in other sections are discussed below

Hydrolysis of Constituent A1: trimethoxy(methyl)silane (CAS 1185-55-3)

Trimethoxy(methyl)silane is one of the constituents of the submission substance. Therefore, where reliable measured data are available for trimethoxy(methyl)silane (CAS 1185-55-3), these are used for the purpose of the chemical safety assessment (CSA) for the relevant endpoints.

For trimethoxy(methyl)silane, hydrolysis half-lives at 25°C of <0.033 h at pH 4, 2.2 h at pH 7 and 0.11 h at pH 9 were determined in accordance with OECD 111 (Dow Corning Corporation 2004). The hydrolysis study measured the decrease in the signal for the nine (9) protons in trimethoxysilane [Si(OCH₃)₃],so the measured hydrolysis half-lives are for the full hydrolysis to the silanetriol. In a supporting reliable study, the stability of the substance in aqueous  media under physiological conditions was investigated. The rates of hydrolysis of 1000 ppm trimethoxy(methyl)silane were determined in water at pH 5.7, 0.15 molar (M) sodium-phosphate buffer (PBS), and 10% rat  serum in  0.15M PBS at pH 7.4 and 37.4°C in soft glass reactors. In this study, the substance was hydrolysed in water, PBS, and PBS plus 10% rat serum at pH 7.4 and 37°C with half-lives of 24, 6.7 and 8.6 minutes respectively. This is also supported by a result in secondary literature of non assignable reliability, which reports a half-life of 23 minutes at pH 5.7 and 37.4°C.

In another supporting study (CRL 2017), 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 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 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.

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 0.00033 h (1.2 seconds) at pH 2 and 25°C, and 0.8 h at pH 7 and 37.5°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 for the substance at pH 2 and 37.5°C is approximately 5 seconds.

The hydrolysis products of trimethoxy(methyl)silane are methylsilanetriol (Silanol HP-X) and methanol.

Hydrolysis of Constituent B1: 3-aminopropyltrimethoxysilane (CAS 13822-56-5)

3-Aminopropyltrimethoxysilane (CAS 13822-56-5) is one of the constituents of the submission substance. Therefore, where reliable measured data are available for 3-aminopropyltrimethoxysilane (CAS 13822-56-5), these are used for the purpose of the CSA for the relevant endpoints.

For 3-aminopropyltrimethoxysilane, hydrolysis half-lives at 20-25°C of 0.2 h at pH 4, 2.6 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods.

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 0.002 h (7.2 seconds) at pH 2 and 25°C, and approximately 1 h at pH 7 and 37.5°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 for the substance at pH 2 and 37.5°C is approximately 5 seconds

The hydrolysis products are 3-aminopropylsilanetriol (Silanol HP-Z) and methanol.

Hydrolysis of Constituent B4: 3-aminopropyltriethoxysilane (CAS 919-30-2)

3-Aminopropyltriethoxysilane (CAS 919-30-2) is one of the constituents of the submission substance. Therefore, where reliable measured data are available for 3-aminopropyltriethoxysilane (CAS 919-30-2), these are used for the purpose of the CSA for the relevant endpoints.

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 in accordance with OECD 111 (Dow Corning Corporation 2001). At pH 4, the substance has a predicted half-life of 0.4 h at 25°C. The hydrolysis study measures the rates of the three consecutive hydrolysis steps and found the first step to be the slowest, i.e., once the first ethoxy group is lost, complete hydrolysis to the silanetriol is rapid.

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 (14 seconds) at pH 2 and 25°C, and 3.1 h at pH 7 and 37.5°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 for the substance at pH 2 and 37.5°C is approximately 5 seconds.

The hydrolysis products are 3-aminopropylsilanetriol (Silanol HP-Z) and ethanol.

Hydrolysis of the read-across substance triethoxy(methyl)silane (CAS 2031-67-6)

Triethoxy(methyl)silane is one of the constituents of the submission substance. Therefore, available data for triethoxy(methyl)silane (CAS 2031-67-6), are used for the purpose of the CSA for the relevant endpoints.

For triethoxy(methyl)silane, hydrolysis half-lives at 20-25°C of 0.3 h at pH 4, 5.9 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods.

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 5 seconds at pH 2 and 25°C, and approximately 2 hours at pH 7 and 37.5°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 for the substance at pH 2 and 37.5°C is approximately 5 seconds

The hydrolysis products are methylsilanetriol (Silanol HP-X) and ethanol.

Hydrolysis of the read-across substance N-ethyl-3-trimethoxysilyl-2-methyl-propanamine (CAS 227085-51-0)

Data for the substance, N-ethyl-3-trimethoxysilyl-2-methyl-propanamine (CAS 227085-51-0) are read-across to the submission substance for the following endpoints, acute toxicity oral, acute toxicity dermal, skin irritation, eye irritation and repeated dose toxicity oral. The hydrolysis half-lives and the silanol hydrolysis product of the two substances are relevant to this read-across, as discussed in the appropriate sections for each endpoint.

For N-ethyl-3-trimethoxysilyl-2-methyl-propanamine, hydrolysis half-lives at 25°C of 0.3 h at pH 4, 4.7 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods.

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 0.003 h (11 seconds) at pH 2 and 25°C, and 1.7 h at pH 7 and 37.5°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 for the substance at pH 2 and 37.5°C is approximately 5 seconds

The hydrolysis products are N-ethyl-3-trihydroxysilyl-2-methylpropanamine and methanol.

 

Hydrolysis of the read-across substance bis(trimethoxysilylpropyl)amine (CAS 82985-35-1)

Data for the substance bis(trimethoxysilylpropyl)amine (CAS 82985-35-1) are read-across to the submission substance for the following endpoints, short-term toxicity to fish, short-term toxicity to aquatic invertebrates, toxicity to algae and toxicitity to microorganisms. The silanol hydrolysis product of the substance is relevant to this read-across, as discussed in the appropriate section for the endpoint.

For bis(trimethoxysilylpropyl)amine, hydrolysis half-lives at 20-25°C of 0.3 h at pH 4, 6.9 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods.

The hydrolysis products are bis(trihydroxysilylpropyl)amine and methanol.

Hydrolysis of the read-across substance N,N-bis(3-triethoxysilylpropyl)amine (CAS 13497-18-2)

Data for the substance N,N-bis(3-triethoxysilylpropyl)amine (CAS 13497-18-2) are read-across to the submission substance for the following endpoints, short-term toxicity to fish, short-term toxicity to aquatic invertebrates and toxicity to aquatic algae. The silanol hydrolysis product of the substance is relevant to this read-across, as discussed in the appropriate sections for each endpoint.

For N,N-bis(3-triethoxysilylpropyl)amine, a preliminary test on the hydrolysis of bis(triethoxysilylpropyl)amine was performed as part of the biodegradation in water test according to OECD Test Guideline 301 and in compliance with GLP. The hydrolysis test was performed in purified water for a test duration of 2 hours. The test item was observed to undergo hydrolysis to ethanol and the respective silanol hydrolysis product. Ethanol was analytically monitored at time points 0 hour, 0.5 hours, 1 hour and 2 hours in order to gather information on the hydrolysis rate of the test item. More than half of the test material (51 – 62%) was hydrolysed right after the preparation of the solution at time point 0 hour. 97-99% of the test material was hydrolysed after 0.5 hours, showing that the substance hydrolyses rapidly in water at alkaline pH (9.5) and room temperature.

In addition, a preliminary hydrolysis study was conducted as part of an adsorption study according to OECD Test Guideline 106. The half-life of the substance was determined in soil eluates of 5 different soil types having neutral pH values (5.5 - 7.2). The parent substance was analytically monitored via LC-MS at time points 0 hour, 0.25 hours, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours and 24 hours. The hydrolysis half-lives were between 1 - 5.6 hours, indicating rapid hydrolysis of the substance in soils of neutral pH.

In conclusion, using the evidence from both studies as weight of evidence; it can be concluded that the substance hydrolyses rapidly and within the trigger value for fast hydrolysis of 12 hours given by the guidelines.

The hydrolysis products are N,N-bis(trihydroxysilylpropyl)amine and ethanol.

Hydrolysis of the read-across substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3)

Data for the substance, N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) are read-across to the submission substance for the long-term toxicity to aquatic invertebrates endpoint. The hydrolysis half-life and formation of similar hydrolysis products are relevant to this read-across as discussed in the appropriate section for the endpoint.

For N-(3-(trimethoxysilyl)propyl)ethylenediamine, measured hydrolysis half-life value of 0.1 h at pH 4 and 24.7°C, 0.025 h at pH 7 and 24.7°C, and 0.32 h at pH 5 and 24.7°C was determined for the substance in accordance with OECD 111. The result is considered to be reliable. At pH >7, the half-life became too rapid (<90 s) to measure using the methodology of this study.

In other secondary sources to which reliability could not be assigned, a hydrolysis half-life of 0.016 h at pH 7 and 24.7°C was reported. Also, a hydrolysis half-life of 24.1 h at 25°C was reported, information on the pH was not stated.

The hydrolysis products are N-(3-(trihydroxysilyl)propyl)ethylenediamine and methanol.

Hydrolysis of the read-across substance triethoxy(3-isocyanatopropyl)silane (CAS 24801-88-5)

Data for the substance, triethoxy(3-isocyanatopropyl)silane (CAS 24801-88-5) are read-across to Constituent B [3-(trimethoxysilyl)propylamine] of the submission substance for the toxicity to microorganisms endpoint. The silanol hydrolysis products and the rate of hydrolysis of the two substances are relevant to this read-across, as discussed in the appropriate section for the endpoint.

Triethoxy(3-isocyanatopropyl)silane, has two hydrolysable groups, trimethoxy (-OCH₃) and isocyanate (-N=C=O). The isocyanate group is expected to hydrolyses very rapidly, for example the hydrolysis half-lives of 2,2,4(or 2,4,4)-trimethylhexane-1,6-diisocyanate were measured in accordance with OECD 111 test method and in compliance with GLP. Very rapid hydrolysis following pseudo-first order kinetics with the following half-lives was determined:

pH 4 - 8.08 min at 10°C, 3.81 min at 20°C and 2.51 min at 30°C

pH 7 - 12.1 min at 10°C, 4.88 min at 20°C and 2.15 min at 30°C

pH 9 - 5.78 min at 10°C, 1.93 min at 20°C and 0.74 min at 30°C

For triethoxy(3-isocyanatopropyl)silane, this means very rapid hydrolysis to form 3-aminopropyltriethoxysilane (CAS 919-30-2) as an intermediate hydrolysis product and carbon dioxide. The hydrolysis half-lives of 3-aminopropyltriethoxysilane (CAS 919-30-2) are discussed above.

The ultimate product of the hydrolysis reaction under dilute conditions is 3-aminopropylsilanetriol (Silanol HP-Z, 1 mole). The other hydrolysis products are ethanol (3 moles) and carbon dioxide (1 mole).

Hydrolysis of read-across substance Trimethoxy(methyl)silane and its reaction products with 3-aminopropyl(trimethoxy)silane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, EC No. 701-408-8

Trimethoxy(methyl)silane and its reaction products with 3-aminopropyl(trimethoxy)silane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, EC No. 701-408-8 is a UVCB substance containing the methoxy constituents of the submission substance. Under the dilute conditions relevant for the environment, the hydrolysis of each constituent can be considered separately. Available data for acute toxicity oral, acute toxicity dermal, skin irritation, eye irritation and repeated dose toxicity oral have been read across.

All the constituents in the read-across substance, trimethoxy(methyl)silane and its reaction products with 3-aminopropyl(trimethoxy)silane and [3-(2,3-epoxypropoxy)propyl]trimethoxysilane, EC No. 701-408-8; are also present in the submission substance except Constituents C2, D2 and G2. The hydrolysis half-lives of these constituents are reported below.

Constituent A: Trimethoxy(methyl)silane, CAS 1185-55-3

Hydrolysis half-lives for Constituent A are discussed above.

 

Constituent B: 3-(Trimethoxysilyl)propylamine, CAS 13822-56-5

Hydrolysis half-lives for Constituent B are discussed above.

 

Constituents C: Disilyl(cycloalkylamine), pentamethoxy-

No measured data are available for the hydrolysis half-lives of Constituents C. Therefore, the half-lives have been predicted using validated QSAR estimation methods as follows:

Constituent C1: 0.4 h at pH 4, 7.9 h at pH 7 and 0.1 h at pH 9 and 20-25°C

Constituent C2: 0.5 h at pH 4, 16 h at pH 7 and 0.2 h at pH 9 and 20-25°C.

The final hydrolysis products under dilute conditions relevant for the environment are disilyl(alkylamine)-heptol (Silanol HP-Y, 1 mole) and methanol (5 moles) for Constituent C1 and disilyl(alkylamine)-heptol (Silanol HP-Y, 1 mole), methylsilanetriol (Silanol HP-X, 1 mole) and methanol (6 moles) for Constituent C2.

 

Constituents D: Trisilyl(alkylamine), octamethoxy-methyl-

No measured data are available for the hydrolysis half-lives of Constituents D. Therefore, the half-lives have been predicted using validated QSAR estimation methods as follows:

Constituent D1: 0.3 h at pH 4, 5.9 h at pH 7 and 0.1 h at pH 9 and 20-25°C

Constituent D2: 0.4 h at pH 4, 12 h at pH 7 and 0.2 h at pH 9 and 20-25°C

The final hydrolysis products under dilute conditions relevant for the environment are disilyl(alkylamine)-heptol (Silanol HP-Y, 1 mole), methylsilanetriol (Silanol HP-X, 1 mole) and methanol (8 moles) for Constituent D1 and disilyl(alkylamine)-heptol (Silanol HP-Y, 1 mole), methylsilanetriol (Silanol HP-X, 2 moles) and methanol (9 moles) for Constituent D2.

Constituents E: Tetrasilyl(alkylamine), decamethoxy-methyl-

No measured data are available for the hydrolysis half-lives of Constituents E. The hydrolysis half-lives have therefore been predicted using validated QSAR estimation methods to be 0.3 h at pH 4, 5.9 h at pH 7, and 0.1 h at pH 9 and 20-25°C. The result is considered to be reliable.

The final hydrolysis products under dilute conditions relevant for the environment are trisilyl(alkylamine) undecol(Silanol HP-W, 1 mole), methylsilanetriol (Silanol HP-X, 1 mole) and methanol (10 moles)

 

 

Constituents F: Pentasilyl(alkylamine), tridecamethoxy-methyl-

No measured data are available for the hydrolysis half-lives of Constituents F. The hydrolysis half-lives have therefore been predicted using validated QSAR estimation methods to be 0.3 h at pH 4, 5.9 h at pH 7, and 0.1 h at pH 9 and 20-25°C. The result is considered to be reliable.

The final hydrolysis products under dilute conditions relevant for the environment are trisilyl(alkylamine) undecol(Silanol HP-W, 1 mole), methylsilanetriol (Silanol HP-X, 2 moles) and methanol (13 moles)

Constituents G: Methyl(methoxy) functional disiloxanes

No measured data are available for the hydrolysis half-lives of Constituents G. Therefore, the half-lives have been predicted using validated QSAR estimation methods as follows:

Constituent G1: 0.4 h at pH 4, 12 h at pH 7 and 0.2 h at pH 9 and 20-25°C

Constituent G2: 0.5 h at pH 4, 16 h at pH 7 and 0.2 h at pH 9 and 20-25°C.

The final hydrolysis products under dilute conditions relevant for the environment are methylsilanetriol (Silanol HP-X, 2 moles) and methanol (4 moles) for Constituent G1 and 3-aminopropylsilanetriol(Silanol HP-Z, 1 mole), methylsilanetriol (Silanol HP-X, 1 mole) and methanol (4 moles) for Constituent G2.