Triethoxy(3-isocyanatopropyl)silane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was not conducted under 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 tiration 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 hydrchloric 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 interatively. The tolerance was set at 0.01%. Convergence was typically reached in 3-4 iterations, although in one case 8 iterations 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 hydrolyse 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 its 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 concentration 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 occurring.

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 was determined at pH 7 at 24.7°C 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-aminopropyltriethoxysilane 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 catalysed 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 hydrolysed to the silanetriol in ≤4.5 days at 25°C.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2012-12-11 to 2012-12-17

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Samples were taken at test start and at a minimum of 8 spaced points, normally between 10 and 90% of hydrolysis, at each test temperature. All test item containing samples were analysed immediately (max. 1% of total incubation time until start of analyses) via LC-MS/MS. Beginning of derivatisation was defined as start of analysis.

Buffers:

Buffer solution pH 4: 45 mL of 0.1 mol/L NaOH were mixed with 250 mL 0.1 mol/L monopotassium citrate and diluted to 500 mL with double distilled water.

Buffer solution pH 7: 148.15 mL of 0.1 mol/L NaOH were mixed with 250 mL 0.1 mol/L KH2PO4 and diluted to 500 mL with double distilled water.

Buffer solution pH 9: 106.5 mL of 0.1 mol/L NaOH were mixed with 2500 mL 0.1 mol/L H3BO3 in 0.1 mol/L KCl and diluted to 500 mL with double distilled water.

Buffers were prepared from chemicals with analytical grade or better quality. Buffers were purged with nitrogen for 5 min. Then the pH was checked to a precision of at least 0.1 at the required temperature.

Details on test conditions:

Co-solvent: Acetonitrile, 10 % (v/v)
Initial test concentration: 100 µg/L
Test vessels: HPLC vials, volume: 4 mL
Test volume: 2 mL
Temperatures (measured every minute): 10.1 ± 0.04, 20.1 ± 0.04 and 30.0 ± 0.05 °C

Duration:

40 min

pH:

4

Temp.:

10

Initial conc. measured:

115 µg/L

Duration:

60 min

pH:

4

Temp.:

20

Initial conc. measured:

110 µg/L

Duration:

8 min

pH:

4

Temp.:

30

Initial conc. measured:

123 µg/L

Duration:

40 min

pH:

7

Temp.:

10

Initial conc. measured:

117 µg/L

Duration:

60 min

pH:

7

Temp.:

20

Initial conc. measured:

125 µg/L

Duration:

9 min

pH:

7

Temp.:

30

Initial conc. measured:

128 µg/L

Duration:

36 min

pH:

9

Temp.:

10

Initial conc. measured:

109 µg/L

Duration:

8 min

pH:

9

Temp.:

20

Initial conc. measured:

103 µg/L

Duration:

5 min

pH:

9

Temp.:

30

Initial conc. measured:

116 µg/L

Number of replicates:

1 replicate each per pH, temperature, and sampling time

Positive controls:

no

Negative controls:

no

Preliminary study:

No preliminary study was performed since hydrolytical lability was known.

Transformation products:

not measured

Key result

pH:

4

Temp.:

10 °C

Hydrolysis rate constant:

0.086 min-1

DT50:

8.08 min

Type:

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

Remarks on result:

other: Confidence interval: 7.42 to 8.71 min

Key result

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0.182 min-1

DT50:

3.81 min

Type:

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

Remarks on result:

other: Confidence interval: 3.4 to 4.21 min

Key result

pH:

4

Temp.:

30 °C

Hydrolysis rate constant:

0.276 min-1

DT50:

2.51 min

Type:

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

Remarks on result:

other: Confidence interval: 2.18 to 2.85 min

Key result

pH:

7

Temp.:

10 °C

Hydrolysis rate constant:

0.057 min-1

DT50:

12.1 min

Type:

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

Remarks on result:

other: Confidence interval: 11.9 to 12.3 min

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.142 min-1

DT50:

4.88 min

Type:

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

Remarks on result:

other: Confidence interval: 4.41 to 5.34 min

Key result

pH:

7

Temp.:

30 °C

Hydrolysis rate constant:

0.322 min-1

DT50:

2.15 min

Type:

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

Remarks on result:

other: Confidence interval: 2.0 to 2.3 min

Key result

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

0.12 min-1

DT50:

5.78 min

Type:

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

Remarks on result:

other: Confidence interval: 5.3 to 6.26 min

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.36 min-1

DT50:

1.93 min

Type:

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

Remarks on result:

other: Confidence interval: 1.73 to 2.12 min

Key result

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

0.26 min-1

DT50:

0.74 min

Type:

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

Remarks on result:

other: Confidence interval: 0.72 to 0.76 min

 

pH 4
	10°C	20°C	30°C
Regression equation	-0.0858x + 3.99	-0.182x + 3.87	-0.276x + 4.00
Correlation factor [r^2]	0.995	0.993	0.955
Reaction rate constant kobs [1/min]	8.58 x 10^-2	1.82 x 10^-1	2.76 x 10^-1
Half life T½ [min]	8.08	3.81	2.51
Confidence interval of half lifeT½ [min]	7.42 to 8.71	3.40 to 4.21	2.18 to 2.85
pH 7
	10°C	20°C	30°C
Regression equation	-0.0574x + 4.04	-0.142x + 3.97	-0.322x + 4.06
Correlation factor [r^2]	0.999	0.993	0.993
Reaction rate constant kobs [1/min]	5.74 x 10^-2	1.42 x 10^-1	3.22 x 10^-1
Half lifeT½ [min]	12.1	4.88	2.15
Confidence interval of half lifeT½ [min]	11.9 to 12.3	4.41 to 5.34	2.00 to 2.30

 

pH 9
	10°C	20°C	30°C
Regression equation	-0.120x + 3.96	-0.360x + 3.76	-0.0156x + 4.06
Correlation factor [r^2]	0.994	0.986	0.999
Reaction rate constant kobs [1/min]	1.20 x 10^-1	3.60 x 10^-1	2.60 x 10^-4
Half lifeT½ [min]	5.78	1.93	0.74
Confidence interval of half lifeT½ [min]	5.30 to 6.25	1.73 to 2.12	0.72 to 0.76

 

Validity criteria fulfilled:

yes

Conclusions:

The hydrolysis of 2,2,4(or 2,4,4)-trimethylhexane-1,6-diisocyanate was studied according to OECD Test Guideline 111 (2004) and Council Regulation (EC) No. 440/2008, Method C.7 with a test item concentration of 100 µg/L in buffer solutions of pH 4, 7 and 9 at temperatures of 10, 20 and 30 °C. Rapid hydrolysis following pseudo-first order kinetics with the following half-lives was observed:
pH 4: 8.08 min (10°C), 3.81 min (20°C), 2.51 min (30°C)
pH 7: 12.1 min (10°C), 4.88 min (20°C), 2.15 min (30°C)
pH 9: 5.78 min (10°C), 1.93 min (20°C), 0.74 min (30°C)

Apparently, the base catalysed hydrolysis is the fastest hydrolysis process.

Executive summary:

The hydrolysis of 2,2,4(or 2,4,4)-trimethylhexane-1,6-diisocyanate was studied according to OECD Test Guideline 111 (2004) and Council Regulation (EC) No. 440/2008, Method C.7 with a test item concentration of 100 µg/L in buffer solutions of pH 4, 7 and 9 at temperatures of 10, 20 and 30 °C. Rapid hydrolysis following pseudo-first order kinetics with the following half-lives was observed:

pH 4: 8.08 min (10°C), 3.81 min (20°C), 2.51 min (30°C)

pH 7: 12.1 min (10°C), 4.88 min (20°C), 2.15 min (30°C)

pH 9: 5.78 min (10°C), 1.93 min (20°C), 0.74 min (30°C).

Apparently the base catalyzed hydrolysis is the fastest hydrolysis process.

Reference 3

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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/QPRF

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:

0.4 h

Remarks on result:

other: 20-25°C

Key result

pH:

5

DT50:

0.4 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, 0.4 h at pH 5 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 (isocyanate group): 3.81 min at pH 4, 4.88 min at pH 7 and 1.93 min at pH 9 and 20°C (OECD 111) based on read-across from 2,2,4(or 2,4,4)-trimethylhexane-1,6-diisocyanate

Hydrolysis half-life (triethoxysilane group): 0.8 h at pH 5, 8.5 h at pH 7, and 0.15 h at pH 9 and 24.7°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

8.5 h

at the temperature of:

24.7 °C

Additional information

There are no reliable measured hydrolysis data for the submission substance. The substance, triethoxy(3-isocyanatopropyl)silane has two types of hydrolysable groups, triethoxy (-OCH₃CH₂) and isocyanate (-N=C=O). The isocyanate group is expected to hydrolyse very rapidly in contact with water, for example the hydrolysis half-lives of 2,2,4(or 2,4,4)-trimethylhexane-1,6-diisocyanate were measured in accordance with OECD Test Guideline 111 and in compliance with GLP (Lange 2013). 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

Similarly, n-butyl isocyanate (CAS 111-36-4) was reported to undergo complete hydrolysis in water within a few minutes at 20°C (OECD 2005).

For the registration substance, 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 have been measured in accordance with OECD 111 to be 0.8 h at pH 5, 8.5 h at pH 7, and 0.15 h at pH 9 and 24.7°C (Dow Corning Corporation 2001a). The quoted results relate to disappearance of parent substance. The measured result is supported by predicted hydrolysis half-lives of 0.4 h at pH 4, 0.4 h at pH 5 and 0.1 h at pH 9 and 20-25°C using a validated QSAR estimation method. In Beari et al (2001), a hydrolysis half-life of <1 hour at pH 6 was reported for the substance.

In the measured study conducted for the intermediate hydrolysis product, two intermediates and the final hydrolyis product were observed and quantified. The substance was found to hydrolyse according to the following reaction scheme:

RSi(OEt)₃ → RSi(OEt)₂(OH) → RSi(OEt)(OH)₂ → RSi(OH)₃

One mole of ethanol is released at each hydrolysis step.

Estimates for the rate constants for the first, second and third reaction steps (k₁, k₂ and k₃ respectively) were obtained; over the range of pH and temperature investigated the intermediate silanol products were found to hydrolyse more rapidly than the original trialkoxysilane. Consequently, these intermediates can be considered transient. The rate constant values obtained for the hydroxonium ion 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 hydroxide ion 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. 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 maxima and begin to decrease more quickly because the ratios of k₂ and k₃ to k₁ are greater than for the acid catalysed reaction.

The pH dependence of the hydrolysis kinetics was investigated, by carrying out experiments at a range of pH values between 4.7 and 9.0. The reaction rate was found to be slowest at pH 6.5 - 7 and increase as the pH was raised or lowered. Estimates of k_H3O+ (the hydroxonium ion catalysed rate constant) for the first, second and third reaction steps; k_OH- (the hydroxide ion catalysed rate constant) for the first and second reaction steps; and k₀ (the solvent catalysed rate constant) for the first reaction step were obtained. These can be used to estimate the reaction rate at any pH for zero buffer concentration.

The temperature dependence of the hydrolysis kinetic was investigated by carrying out experiments at 10, 25 and 35°C. The reaction rate was found to increase with temperature, to a greater extent for the hydroxide catalysed reaction than the hydronium ion catalysed reaction. Arrhenius parameters were calculated for the hydronium and hydroxide calculated reactions and these can be used to estimate the reaction rate at any temperature.

The authors of this summary have used the rate constants and Arrhenius parameters quoted in the study report to calculate the half-lives in the table below for a range of relevant temperature and pH values.

Table1: Estimated half-lives at a range of temperature and pH values.

Temperature /°C	pH	Relevance	Half-life
20	7	Ecotoxicology studies	11 h
20	8	Ecotoxicology studies	2.6 h
20	9	Ecotoxicology studies	0.3 h
37.5	7	Toxicology, lungs and blood	3.4 h
37.5	5.5	Toxicology, skin	1.4 h
37.5	2	Toxicology, stomach	5 s^a
35	4.7	Boundary of experimental results	15 mins

^aThe calculated value is 2 s. However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. Therefore, the value is reported as 5 s.

The measurements in the study were taken at pH 4.7 - 9.0 and 10 - 35°C; therefore, the estimates at 37.5°C and pH 2 represent extrapolations. The difference between 35°C and 37.5°C is very small, so this extrapolation is not considered to add significant uncertainty to the results. The estimated result at pH 2 does represent an extrapolation significantly outside the range of pH values studied (4.7 - 9.0). However, the study results are strongly supportive of a hydroxonium ion catalysed reaction being dominant in the acid pH range (4.7-5.9) and the reaction rate increasing as the hydroxonium ion concentration increases (pH decreases). Therefore, it is extremely unlikely that the hydrolysis at pH 2 is slower than that at pH 4.7.

The ultimate product of the hydrolysis reaction under dilute condition is 3-aminopropylsilanetriol. The other hydrolysis products are ethanol and carbon dioxide.

The hydrolysis of other substances used for read-across in other sections are discussed below.

Hydrolysis of the read-across substance 3-aminopropyltriethoxysilane (CAS 919-30-2)

3-Aminopropyltriethoxysilane (CAS 919-30-2) is the intermediate hydrolysis product of triethoxy(3-isocyanatopropyl)silane. Therefore, available data for 3-aminopropyltriethoxysilane (CAS 919-30-2) are read across to the submission substance triethoxy(3-isocyanaotopropyl)silane for the following endpoints, short-term toxicity to fish, short-term toxicity to aquatic invertebrates, toxicity to aquatic algae, repeated dose toxicity: oral, toxicity to reproductive toxicity and developmental toxicity. Following the very rapid hydrolysis of the isocyanate group in triethoxy(3-isocyanatopropyl)silane, the read across substance; 3-aminopropyltriethoxysilane is the intermediate hydrolysis product.

Further information on the hydrolysis half-lives of 3-aminopropyltriethoxysilane are discussed as part of the hydrolysis of the submission substance above.

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, triethoxy(3-isocyanatopropyl)silane for the long-term toxicity to aquatic invertebrates endpoint. The hydrolysis half-lives and the silanol hydrolysis products of the two substances are relevant to this read-across, as discussed in the appropriate section for the endpoint.

For N-[3-(trimethoxysilyl)propyl]ethylenediamine, hydrolysis half-lives at 24.7°C of 0.1 h at pH 4, 0.32 h at pH 5, and 0.025 h at pH 7 were determined in accordance with OECD 111 (Dow Corning Corporation 2001b). 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 at 24.7°C and a hydrolysis half-life of 24.1 h at 25°C (information on pH was not stated) were reported.

The complete hydrolysis of CAS 1760-24-3 involves consecutive removal of the three methoxy groups; it is therefore a three-step process. The quoted half-lives refer to degradation of parent substance. In addition, separate rate constants for the threeconsecutive hydrolysis reactions have been measured. For the acid catalysed rate constants, the second and third reaction steps were found to be approximately twice as fast as the previous step (k₁<k₂<k₃). For the base catalysed rate constants, the second step was found to be approximately 1.5-fold slower than the first step which was about the same as the third step (k₂<k₁≈k₃). Therefore, rapid formation of the final product is expected across the pH range.

The hydrolysis products areN-(3-(trihydroxysilyl)propyl)ethylenediamine (1 mole) and methanol (3 moles).

Hydrolysis of the read-across substance 3-(trimethoxysilyl)propyl isocyanate (CAS 15396-00-6)

Data for the substance, 3-(trimethoxysilyl)propyl isocyanate (CAS 15396-00-6) are read-across to the submission substance, triethoxy(3-isocyanatopropyl)silane for the following endpoints; short-term toxicity to fish and short-term toxicity to aquatic invertebrates. 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 for each endpoint.

 

For 3-(trimethoxysilyl)propyl isocyanate, the isocyanate group is expected to hydrolyse very rapidly to form 3-aminopropyltrimethoxysilane (CAS 13822-56-6) as an intermediate hydrolysis product and carbon dioxide. The hydrolysis half-lives of 3-aminopropyltrimethoxysilane 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. Also, hydrolysis half-life of (3-isocyanatopropyl)trimethoxysilane was found to be much less than 2.4 h at pH 4, pH 7 and pH 9 and 50°C. Therefore, the half-lives at 25°C and pH 4, pH 7 and pH 9, were estimated to be <1 day, which is consistent with the expected behaviour. The study was conducted according to OECD Test Guideline 111 (1981) and in compliance with GLP; the results are considered reliable. However, according to the most recent version of the test guideline, a higher-tier test should be carried out if a substance is found to be unstable in the preliminary test and this was not done in this study. However, in view of the extreme instability of the isocyanate group, in practice it may not be technically feasible to do so and obtaining a more accurate half-life value would be of limited use.

 

The hydrolysis products are 3-aminopropylsilanetriol, methanol and carbon dioxide.

The table below summarises all relevant hydrolysis half-lives used in this chemical safety assessment:

  Table: Summary of relevant hydrolysis half-lives

Name	CAS No	Half-lives at 20-25°C				Half-lives at 37.5°C
		pH 4	pH 5	pH 7	pH 9	pH 2	pH 5.5	pH 7
2,2,4 (or 2,4,4)-Trimethylhexane-1,6-diisocyanate	32052-51-0	3.81 minute*	-	4.88 minute*	1.93 minute*	-		-
3-(Trimethoxysilyl)propyl isocyanate	15396-00-6	0.2 hour**	0.3 hour**	2.8 hour**	0.1 hour**	-		-
3-Aminopropyltrimethoxysilane	13822-56-5	0.2 hour**	0.3 hour**	2.6 hour**	0.1 hour**	5 seconds	0.1 – 1 hour	1 hour
3-Aminopropyltriethoxysilane	919-30-2	0.4 hour**	0.8 hour*	8.5 hour*	0.15 hour*	5 seconds	0.15 – 3 hour	3 hour
N-[3-(trimethoxysilyl)propyl]ethylenediamine	1760-24-3	0.1 h*	0.32 h*	0.025 h*

*measured

**predicted

-not calculated

 

References:

Lange (2013).Lange, J. (2013). Vestanat TMDI - hydrolysis as a function of pH. Dr. U. Noack-Laboratorien, Sarstedt (Germany). Test report. Testing laboratory: Dr. U. Noack-Laboratorien, Sarstedt (Germany). Report no.: CPH14411. Owner company: Evonik lndustries AG. Report date: 2013-01-21.

OECD (2005). SIDS Initial Assessment Report for SIAM 21, Washington, 18-21 October 2005, n-Butyl isocyanate, CAS 111-36-4.