3-(triethoxysilyl)propiononitrile

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-12-09 to 2004-07-01

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:

yes

Remarks:

A 0.128 M phosphate buffer was used as this was commercially available and ready to use with specification; this had no impact on the study.

GLP compliance:

yes (incl. QA statement)

Details on sampling:

At each sampling point, 2.5 ml hydrolysis solution were transferred into a 10 ml volumetric flask. The volume was made up to the mark with acetone. After filtration (0.2 µm), the samples were subjected to GC analysis. The samples from the duplicate hydrolysis test at 10°C were stored on ice until GC analysis (ca. 25 min).

Buffers:

Buffer system and concentrations:
- 0.05 M biphthalate buffer for pH 4.00 ± 0.02 (20°C)
- 0.128 M phosphate buffer for pH 7.00 ± 0.02 (20°C)
- 0.05 M borate buffer for pH 9.00 ± 0.02 (20°C)

The pH of each buffer was checked prior to use with pH indicator strips.

Number of replicates:

Two at each pH and temperature.

Statistical methods:

The concentration/time data were plotted as ln c(t) versus t (where t is the time and c(t) is the concentration of test substance at time t). The linear plot showed that the data fitted to the equation ln c(t) = (-k) t - ln c(0) (where k is the rate constant and c(0) is the initial concentration of test substance) and, therefore, the reaction is pseudo first order. The rate constant was calculated by linear regression analysis and the half-life as t1/2 = ln 2 / k.

The coefficients of the regressions were 0.894 and 0.896 for pH 7.0 and 10°C, 0.967 and 0.959 for pH 7.0 and 20°C and 0.997 1.000 for pH 9.0 and 10°C.

Preliminary study:

The preliminary test at 50°C was not conducted since the test substance was observed to be hydrolytically unstable (t1/2 < 1 year) during GC-method development.

Transformation products:

yes

No.:

#1

No.:

#2

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

Quantification and characterization of hydrolysis products was not performed. 
The degradation products are expected to be:
- CAS 182156-21-4, 3-Trihydroxysilyl-propanenitrile, (2-cyanoethyl)silantriol
- CAS 64-17-5, EC 200-578-6, ethanol

Key result

pH:

4

Temp.:

10 °C

DT50:

< 0.5 h

Type:

other: Estimate of upper limit of hydrolysis half-life

Remarks on result:

other: Degradation was too rapid for kinetic parameter determination

Key result

pH:

4

Temp.:

20 °C

DT50:

< 0.5 h

Type:

other: Estimate of upper limit of hydrolysis half-life

Remarks on result:

other: Degradation was too rapid for kinetic parameter determination

Key result

pH:

7

Temp.:

10 °C

Hydrolysis rate constant:

0.048 h-1

DT50:

14.5 h

Type:

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

Remarks on result:

other: Mean of duplicate samples (t1/2 = 13.6 h and 15.6 h)

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.106 h-1

DT50:

6.5 h

Type:

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

Remarks on result:

other: Mean of duplicate samples (t1/2 = 6.5 for both)

Key result

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

0.106 h-1

DT50:

0.6 h

Type:

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

Remarks on result:

other: Mean of duplicate samples (t1/2 = 0.56 and 0.65)

Key result

pH:

9

Temp.:

20 °C

DT50:

< 0.5 h

Type:

other: Estimate of upper limit of hydrolysis half-life

Remarks on result:

other: Degradation was too rapid for kinetic parameter determination

The hydrolytic degradation at pH 4.0 at 10°C and 20°C and pH 9.0 at 20°C was found to be very fast and, therefore, no kinetic parameters could be evaluated. Considerable degradation was proposed to have occured in the t₀ samples as the concentrations measured at the beginning were much lower than at pH 7.0. Based on the measured concentrations at t₀ and t₁, it can be concluded that there was more than one half-life between t₀ and t₁.

At pH 7.0 and 10°C, 11 data points were analysed in each duplicate and at least 8 data points were used for the evaluation of the kinetic data and half-life. The data in the range 22% to 44% degradation for sample 1 and 20% to 45% degradation (142.6 to 261.3 µg/l) in sample 2 were plotted as ln c(t) versus t. Measured concentrations were in the range 139.5 to 250.7 µg/l for sample 1 and 142.6 - 261.3 µg/l for sample 2.

At pH 7.0 and 20°C, 10 data points were analysed in each duplicate and 8 data points were used for the evaluation of the kinetic data and half-life. The data in the range 31% to 60% degradation for sample 1 and 31% to 63% degradation in sample 2 were plotted as ln c(t) versus t. Measured concentrations were in the range 51.4 to 128.0 µg/l for sample 1 and 50.2 to 135.4 µg/l for sample 2.

At pH 9.0 and 10°C, only 3 (sample 1) or 4 (sample 2) data points were measured due to the rapid hydrolysis. Using all data points from 0% to 68% degradation (sample 1) and 0 to 73% degradation (sample 2), the data could be used for the estimation of a half-life. Measured concentrations were in the range 33.7 to 105.4 µg/l for sample 1 and 35.1 to 129.7 µg/l for sample 2.

Hydrolysis was found to be slower by a factor of 2.23 at 10°C than at 20°C, which is in good agreement with the rules of Arrhenius.

Conclusions:

Hydrolysis half-lives at 20°C of <0.5 h at pH 4, 6.5 h at pH 7 and < 0.5 h at pH 9 were determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Executive summary:

The hydrolysis of the test item 3-(triethoxysilyl)propiononitrile was performed at pH 4.0, pH 7.0 and pH 9.0 at 10±0.1°C and at 20 ±0.1°C. The disappearance of the test substance was observed using GC-FID.

At 20°C, very rapid hydrolysis was observed at pH 4.0 and 9.0. Hydrolysis started immediately after preparing the hydrolysis solutions and already in the t₀ samples a considerable amount of the test item had hydrolysed. After about 1 h, practically no test item could be detected in the samples. No kinetics could be measured, but the half-life was estimated to be less than 0.5 h. At pH 7.0, rapid hydrolysis with a half-life of 6.5 h was observed.

At 10°C, rapid hydrolysis was observed a pH 4.0 and 9.0. The half-life at pH 9.0 was determined to be 0.6 h and was estimated to be less than 0.5 h at pH 4.0. At pH 7.0, the test item hydrolysed with an average half-life of 14.5 h.

Description of key information

Hydrolysis half-Life: <0.5 h at pH 4, 6.5 h at pH 7 and <0.5 h at pH 9 and 20°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

6.5 h

at the temperature of:

20 °C

Additional information

A measured hydrolysis half-life value of <0.5 h at pH 4, 6.5 h at pH 7 and <0.5 h at pH 9 and 20°C was determined for the substance in accordance with OECD 111 and in compliance with GLP. The result is considered to be reliable.

The available data do not assess the stability of the propiononitrile side-chain. However, the nitrile group is generally stable except under conditions of high temperature and low or high pH and significant hydrolysis is not expected under environmentally-relevant conditions.

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^-3and 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

The calculated half-life of the substance at pH 2 and 20°C is therefore <0.005 hours (18 seconds).

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT₅₀(XºC) = DT₅₀(T) x e^(0.08.(T-X))

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

Thus, the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 1.6 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature to the limit value and the hydrolysis half-life is therefore approximately 5 seconds.

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

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

Data for 3-aminopropyltriethoxysilane, CAS 919-30-2 are read-across to the submission substance, 3-(triethoxysilyl)propiononitrile for the biodegradation in water endpoint. The hydrolysis half-lives and the formation of analogous silanol hydrolysis products are relevant to this read-across, as discussed in the section for the endpoint.

 

For 3-aminopropyltriethoxysilane, hydrolysis half-lives at 24.7°C of 0.8 h at pH 5, 8.5 h at pH 7 and 0.15 h at pH 9 were determined for the substance in accordance with OECD 111 (5.1.2.067, Dow Corning Corporation 2001). The measured result is supported by predicted hydrolysis half-lives of 0.4 h at pH 4 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.

 

The final hydrolysis products are 3-aminopropylsilanetriol and ethanol.

Hydrolysis of the read-across substance 3-(trimethoxysilyl)propiononitrile (CAS 2526-62-7)

Data for 3-(trimethoxysilyl)propiononitrile, CAS 2526-62-7 are read-across to the submission substance, 3-(triethoxysilyl)propiononitrile for the biodegradation in water, skin irritation and eye irritation endpoints. The hydrolysis half-lives and the formation of the same silanol hydrolysis product are relevant to this read-across, as discussed in each section for the endpoints.

 

For 3-(trimethoxysilyl)propiononitrile, hydrolysis half-lives at 20-25°C of 0.1 h at pH 4, 1.1 h at pH 7 and 0.02 h at pH 9 were predicted for the substance using validated QSAR estimation methods. In a secondary source, a half-life of 48 minutes at 25°C was reported for the substance, with no information on pH reported.

 

The final hydrolysis products are 3-(trihydroxysilyl)propiononitrile and methanol.