N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

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).

GLP compliance:

no

Estimation method (if used):

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

Transformation products:

yes

No.:

#1

No.:

#2

pH:

7

DT50:

4.3 h

Type:

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

Remarks on result:

other: 20-25 °C

pH:

4

DT50:

0.3 h

Type:

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

Remarks on result:

other: 20-25 °C

pH:

9

DT50:

0.1 h

Type:

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

Remarks on result:

other: 20-25 °C

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

Validity criteria fulfilled:

not applicable

Conclusions:

A hydrolysis half life of approximately 4.3 h at 20-25°C and pH 7 was obtained using an appropriate calculation method. The result is considered to be reliable.

Reference 2

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

pH:

4

Temp.:

24.7 °C

DT50:

0.1 h

pH:

5

Temp.:

24.7 °C

DT50:

0.32 h

pH:

7

Temp.:

24.7 °C

DT50:

0.025 h

Description of key information

N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine (CAS 35141-30-1): hydrolysis half-life = 4.3 h at 20 -25 °C and pH 7

Key value for chemical safety assessment

Half-life for hydrolysis:

4.3 h

Additional information

A hydrolysis half-life of approximately 4.3 h at 20-25°C and pH 7 was obtained for the substance using an appropriate calculation method. The result is considered to be reliable and has been assigned as key study.

A QSAR that was developed by Peter Fisk Associates (2013 and 2014, see attached QMRF in IUCLID section 5.1.2) predicts half-lives at 20-25°C of 0.3 h at pH 4, 4.3 h at pH 7 and 0.1 h at pH 9. 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.

kobs= k0+ kH3O+[H3O+] + kOH-[OH-] + ka[acid] + kb[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. This is supported by studies for various organosilicon compounds in which calculation of kH3O+ and kOH- from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7 (Peter Fisk Associates 2016).

Therefore, at low pH:

kobs˜kH3O+[H3O+]

At pH 4 [H3O+]=10-4mol dm-3and at pH2 [H3O+]=10-2mol dm-3; therefore, kobsat pH 2 should be approximately 100 times greater than kobsat pH 4.

The half-life of a substance at pH 2 is calculated based on:

t1/2(pH 2) = t1/2(pH 4) / 100

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions and the half-lives at 37.5°C (relevant for in vivo studies) are expected to be faster than those at 20-25°C. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT50(X°C) = DT50(T) x e(0.08*(T-X))

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

Thus, for N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine (CAS 35141-30-1) the hydrolysis half-life at 37.5°C and pH 7 (relevant for lungs and blood) is 1.06 - 1.58 h (T= 20 – 25°C). At 37.5°C and pH 2 (relevant for the conditions in the stomach following oral exposure) is 4.5 min.

The initial hydrolysis products are N-(2-aminoethyl)-N'-[3-(trihydroxysilyl)propyl]ethylenediamine and methanol.

An experimental study with the structurally related substance, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (CAS 1760-24-3) supports the rapid hydrolysis as predicted by (Q)SAR for N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine (CAS 35141-30-1). A measured 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 N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (CAS 1760-24-3).