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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
GLP compliance:
no
Specific details on test material used for the study:
Not applicable.
Analytical monitoring:
yes
Details on sampling:
direct sample infusion
Buffers:
Ammonium acetate and imidazole buffers of varying concentrations.
Details on test conditions:
No data
pH:
4
Temp.:
24.7 °C
pH:
5
Temp.:
24.7 °C
pH:
7
Number of replicates:
multiple at pH and temperature of interest.
Statistical methods:
The data were modeled by multiple linear regression to determine quantitatively the effect of pH, i.e. hydronium ion concentration, and buffer concentration on rates of hydrolysis.
Preliminary study:
No data
Transformation products:
yes
No.:
#1
No.:
#2
Key result
pH:
4
Temp.:
24.7 °C
DT50:
0.1 h
Key result
pH:
5
Temp.:
24.7 °C
DT50:
0.32 h
Key result
pH:
7
Temp.:
24.7 °C
DT50:
0.025 h

 

pH

Temperature (°C)

Half-life (hr)

4

10.0

0.23

4

24.7

0.10

4

37.0

0.066

5

10.0

1.5

5

24.7

0.32

5

37.0

0.26

7

10.0

0.10

7

24.7

0.025

7

37.0

0.0090

 

Constant (units)

1sthydrolysis step

2ndstep

3rdstep

kH3O+ (M-1 s-1)

16.8

36.0

75.0

kNH3 (s-1)

1.36x10-2

5.24x10-3

N/A (a)

k0, est. (s-1)

2.7x10-4

5.2x10-4

5.1x10-3

 

 

 

 

(a)  Data not sufficiently precise for pH>6.4 to yield reliable estimate

Conclusions:
Hydrolysis half lifes at 24.7°C of 0.1 h at pH 4, 0.32 h at pH 5 and 0.025 h at pH7 were determined in a reliable study conducted according to an appropriate test protocol, but not in compliance with GLP.

Description of key information

Hydrolysis half-lives: 0.1 h at pH 4, 0.32 h at pH 5, 0.025 h at pH 7 and 24.7°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:
0.025 h
at the temperature of:
24.7 °C

Additional information

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 the substance in accordance with OECD 111. The result is considered to be reliable and has been assigned as key study. 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, 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.

In addition, hydrolysis in soil conditioned 0.01 M CaCl2 solution and in wet soil was investigated in preparation for an adsorption/desorption study (see IUCLID dossier Section 5.4.1, Landsberg 2017). The measured half-lives in soil conditioned 0.01 M CaCl2 solution were as follows: Eurosoil 2 (pH 7.9) 0.015 h, Eurosoil 3 (pH 6.0) 0.084 h, Eurosoil 4 (pH 7.5) 0.021 h, LUFA 2.4 (pH 7.8) 0.015 h, LUFA 5M (pH 7.7) 0.015 h. Concentrations in soil samples were found to decrease within 5 minutes, indicating that the substance is unstable; half-lives were not determined.

The complete hydrolysis of CAS No. 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 three consecutive 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.

It is noted that the half-life is slower at pH 5 than at pH 7 and pH 4. In general, alkoxysilane hydrolysis is slowest at around pH 7 and faster as the pH is raised or lowered. However, a possible intermolecular catalysis mechanism has been identified for this substance which speeds up the hydrolysis at pH 7 relative to that observed for similar alkoxysilanes. This different mechanism is proposed as the cause of the different pH-dependent behaviour.

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]

 

Therefore, at low pH:

kobs≈kH3O+[H3O+]

 

At pH 4 [H3O+]=10-4mol dm-3and at pH 2 [H3O+]=10-2mol dm-3; therefore, kobs at 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

The calculated half-life of N-(3-(trimethoxysilyl)propyl)ethylenediamine at pH 2 is therefore 0.001 hours (3.6 seconds). However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10. As a worst-case it can therefore be considered that the half-life for the substance at pH 2 and 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 N-(3-(trimethoxysilyl)propyl)ethylenediamine the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 0.0089 hours (32 seconds). 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 products of hydrolysis are N-(3-(trihydroxysilyl)propyl)ethylenediamine and methanol.