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Reference
Endpoint:
hydrolysis
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Calculated using a suitable predictive method
Justification for type of information:
QSAR prediction
Principles of method if other than guideline:
The result was obtained using an appropriate QSAR method.
GLP compliance:
no
Transformation products:
not specified
pH:
4
DT50:
0.2 h
Remarks on result:
other: 20-25°C
pH:
7
DT50:
4 h
Remarks on result:
other: 20-25°C
pH:
9
DT50:
0.07 h
Remarks on result:
other: 20-25°C

Outcome: The substance is hydrolytically unstable with a half-life of 0.2 h at pH 4 and 0.07 h at pH 9 and 20-25°C.

Outcome: The substance is hydrolytically unstable with a half-life of 4 h at pH 7 at 20-25°C.

Conclusion: The accuracy of the prediction is considered sufficient for the regulatory purpose.

Conclusions:
The predicited hydrolysis half life of N-[3-(trimethoxysilyl)propyl]butylamine is 3.6 hours at 20-25°C and pH 7 was obtained using an accepted QSAR

Description of key information

DT50 (pH 7, 20 - 25 °C) = 4.0 h (QSAR)

Key value for chemical safety assessment

Half-life for hydrolysis:
4 h
at the temperature of:
20 °C

Additional information

Please note: A study according to OECD guideline 111 is ongoing. The dossier will be updated once the final study report is available.


 


A half-life value of approximately 4.0 h at 20-25°C and pH 7 was obtained using an accepted validated QSAR method (Peter Fisk Associates 2012a). The result is considered to be reliable and has been assigned as key study.


A QSAR that is currently being developed (Peter Fisk Associates 2012b) predicts half-lives at 20-25°C of 0.2 h at pH 4 and 0.3 at pH 5 and 0.07 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 2012b).


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


The calculated half-life ofN-[3-(trimethoxysilyl) propyl]butylamine at pH 2 is therefore 5 seconds. However, it is likely that factors such as diffusion become rate-determining when the half-life is less than 5-10 seconds. As a worst-case it can therefore be considered that the half-life forN-[3-(trimethoxysilyl) propyl]butylamineat 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 N-[3-(trimethoxysilyl) propyl]butylaminethe hydrolysis half-life 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.