3-(trimethoxysilyl)propiononitrile

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

See attached QMRFs/QPRFs

Principles of method if other than guideline:

The result was obtained using an appropriate QSAR method (see attached QMRF and QPRF for details)

The model for hydrolysis at pH 7 has been developed for, and applies specifically to, di- and tri-alkoxysilanes. It is a multiple linear regression based model with descriptors representing (i) steric effects of the alkoxy group, (ii) steric effects of the side-chain(s), and (iii) electronic effects of the side-chain(s).

The models for hydrolysis at pH 4, 5 and 9 have been developed for, and applies specifically to, organosilicon compounds. They are linear regression based models where the descriptor is the half-life at pH 7.

Transformation products:

yes

No.:

#1

No.:

#2

Key result

pH:

4

DT50:

0.1 h

Remarks on result:

other: 20-25°C

Key result

pH:

5

DT50:

0.2 h

Remarks on result:

other: 20-25°C

Key result

pH:

7

DT50:

1.1 h

Remarks on result:

other: 20-25°C

Key result

pH:

9

DT50:

0.02 h

Remarks on result:

other: 20-25°C

Conclusions:

Hydrolysis half-life values at 20-25°C of 0.1 h at pH 4, 0.2 h at pH 5, 1.1 h at pH 7 and 0.02 h at pH 9 were obtained using an accepted calculation method. The result is considered to be reliable.

Description of key information

Hydrolysis half-life: 0.1 h at pH 4, 1.1 h at pH 7, and 0.02 h at pH 9 and 20-25°C (QSAR)

Additional information

The hydrolysis half-lives of 3-(trimethoxysilyl)propiononitrile have been predicted using a validated QSAR estimation method to be 0.1 h at pH 4, 0.2 h at pH 5, 1.1 h at pH 7, and 0.02 h at pH 9 and 20-25°C. The result is considered to be reliable and is selected as key study. In a secondary source to which reliability could not be assigned, a hydrolysis half-life of 48 minutes at 25°C and pH 6.5 was reported for the substance.

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.

Hydrolysis reactions of alkoxysilanes can be catalysed by both acid and base. The rate of hydrolysis is slowest close to pH 7 and increases as the pH is raised or lowered. For an acid-base catalysed reaction in buffered solution, the measured rate constant is a linear combination of terms describing contributions from the uncatalyzed reaction as well as catalysis by hydronium, hydroxide, and general acids or bases.

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, the rate of hydrolysis is dominated by either the hydronium or hydroxide catalysed mechanism. This is supported by studies for various organosilicon compounds in which calculation of k_H3O⁺ and k_OH^- from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7.

 

Therefore, at low pH:

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

The calculated half-life of 3-(trimethoxysilyl)propiononitrile at pH 2 and 20-25°C is therefore 0.001 hours (approximately 4 seconds). However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life of the substance at pH 2 and 20-25°C is approximately 5 seconds.

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

DT₅₀(XºC) = DT₅₀(T) x e^(0.08.(T-X))

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

Thus, for 3-(trimethoxysilyl)propiononitrile the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 0.4 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 final hydrolysis products are 3-(trihydroxysilyl)propiononitrile and methanol.

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

The hydrolysis data for 3-aminopropyltriethoxysilane (CAS 919-30-2) are now discussed. Data for this substance are read-across to the submission substance, 3-(trimethoxysilyl)propiononitrile for appropriate endpoint(s) (e.g. ready biodegradation). 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-aminopropyltriethoxysilane, hydrolysis half-lives at 24.7°C of 0.8 h at pH 5, 8.5 h at pH 7 and 0.15 h at pH 9 were determined for the substance in accordance with OECD 111 (5.1.2.067, Dow Corning Corporation 2001). At pH 4, a predicted half-life of 0.4 h at 20-25°C was determined for the substance using a validated QSAR estimation method.

 

The half-lives at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C may be calculated in the same way as for the registration substance above. This gives a half-life of 0.004 h (approximately 14 seconds) at pH 2 and 20-25°C, approximately 5 seconds at pH 2 and 37.5°C and approximately 3 hours at pH 7 and 37.5°C.

The final hydrolysis products are 3-aminopropylsilanetriol and ethanol.

 Hydrolysis half-lives for the read-across substance 3-(triethoxysilyl)propiononitrile (CAS 919-31-3)

Data for the substance 3-(triethoxysilyl)propiononitrile (CAS 919-31-3) are read-across to the submission substance for appropriate endpoints. The rapid hydrolysis of the two substances is relevant to this read-across, as discussed in the appropriate sections for each endpoint(s) (e.g. short-term toxicity to fish, aquatic invertebrate, toxicity to aquatic algae, toxicity to microorganisms, acute toxicity - oral, dermal, skin sensitisation, bacteria mutagenicity, mammalian cytogenicity and reproduction toxicity).

For 3-(triethoxysilyl)propiononitrile, 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 according to OECD 111 (Tognucci, A. 2004).

The half-lives at pH 2 and 20°C, at pH 7 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 <0.005 h (<18 seconds) at pH 2 and 20°C, 4.4 h at pH 7 and 25°C, 1.6 h at pH 7 and 37.5°C, and <0.001 h (<4 seconds) at pH 2 and 37.5°C. As above, the half-life for the substance at pH 2 and 37.5°C is estimated as approximately 5 seconds.

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