Bis(trimethoxysilylpropyl)amine

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Please refer to attached justification documents

Principles of method if other than guideline:

The result was obtained using an appropriate QSAR method.

GLP compliance:

no

Transformation products:

yes

No.:

#1

No.:

#2

pH:

4

DT50:

0.3 h

Remarks on result:

other: 20 - 25 °C

pH:

7

DT50:

6.9 h

Remarks on result:

other: 20 - 25 °C

pH:

9

DT50:

0.1 h

Remarks on result:

other: 20 - 25 °C

pH:

2

Temp.:

37.5 °C

DT50:

0.083 min

Conclusions:

The predicted hydrolysis half life of bis(trimethoxysilylpropyl)amine is 6.9 hours at 20 °C and pH 7 was obtained using an accepted QSAR model.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

- The test item is prone to hydrolysis. Therefore in the frame of the biodegradation test (see cross reference) according to national standards, a preliminary test on the hydrolysis of the substance was performed. The hydrolysis test was performed in purified water for 2 h duration. The test item hydrolyses to methanol and a silanol hydrolysis product. Methanol was analytically monitored at several timepoints in order to gather information on the hydrolysis rate of the test item.

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: samples were taken just after preparation of the test solution and after 0.5, 1 and 2 h.
- Sampling method: 2 mL were taken from the test solution.

Details on test conditions:

TEST MEDIUM
- Volume used/treatment: 300 mL
- Kind and purity of water: purified water
- Preparation of test solution: In each test vessel, 29.0 µL (test item 30.2 mg) of the test sample was taken out by microsyringe and added to 300 mL of stirring purified water, so that the concentration of the test item reached 100 mg/L.

OTHER TEST CONDITIONS
- Adjustment of pH: not mentioned

Duration:

2 h

Remarks:

initial concentration of test item added: 100 mg/L (corresponds to 17 mg methanol). Room Temperature

Number of replicates:

2

Negative controls:

no

Transformation products:

yes

No.:

#1

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

- Formation of transformation product during test: the produced amount of methanol reached to the theoretical amount already at the first measurement just after preparation of the solution, showing that the test item hydrolyzes rapidly.

Remarks on result:

other: see field "details on results"

Details on results:

- The produced amount of methanol reached to the theoretical amount already at the first measurement just after preparation of the solution, showing that the test item hydrolyzes rapidly.

Table 1: Produced amount of methanol (in mg and %)

Sampling Point		Production of methanol (GC)
		just after preparation	0.5 h	1 h	2 h
water + test item_1	mg	16.4	16.1	16.4	16.5
	%	96	95	96	97
water + test item_2	mg	16.4	16.3	16.3	16.4
	%	96	96	96	96
Theoretical amount		17

Validity criteria fulfilled:

not applicable

Conclusions:

The test item is prone to hydrolysis. Therefore in the frame of the biodegradation study, a preliminary test on the hydrolysis of the substance was performed. Since the test item hydrolyses to methanol and a silanol hydrolysis product, methanol was analytically monitored at several timepoints in order to gather information on the hydrolysis rate of the test item. The produced amount of methanol reached to the theoretical amount already at the first measurement just after preparation of the solution, showing that the test item hydrolyzes rapidly.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

- The test item is prone to hydrolysis. Therefore in the frame of the environmental toxicity studies (see cross references) conducted according to national standards, a preliminary test on the hydrolysis of the substance was performed. The hydrolysis test was performed in purified water for 2 h duration. The test item hydrolyses to methanol and a silanol hydrolysis product. Methanol was analytically monitored at several timepoints in order to gather information on the hydrolysis rate of the test item.

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: samples were taken just after preparation of the test solution and after 0.5, 1 and 2 h.

Details on test conditions:

TEST MEDIUM
- Kind and purity of water: ultra pure water.
- Preparation of test solutions: test samples and ultra pure water were mixed and stirred.

Duration:

2 h

Initial conc. measured:

156 mg/L

Remarks:

Temperature: Room Temperature

Number of replicates:

Not reported

Positive controls:

not specified

Negative controls:

no

Transformation products:

yes

No.:

#1

Remarks on result:

other: see field "details on results"

Details on results:

- The produced amount of methanol reached to the theoretical amount already at the first measurement just after preparation of the solution, showing that the test item hydrolyzes rapidly.

It was considered that hydrolysis was completed when theoretical formed concentration of the methanol was detected.

Table 1: measured concentrations of methanol.

Settlement time [h]	Measured Concentration (mg/L) (% of measured concentration versus theoretical formed concentration)*
0	82.8 (94.3)
0.5	83.6 (95.2)
1	86.4 (98.5)
2	89.5 (102)

* Theoretical formed concentration is 87.8 mg/L

The concentration of methanol was 94.3% of the theoretical formed concentration right after preparation and 102% after 2 h. Therefore the test item is hydrolyzed completely within 2 h.

Validity criteria fulfilled:

not applicable

Conclusions:

The test item is prone to hydrolysis. Therefore in the frame of environmental toxicity studies, a preliminary test on the hydrolysis of the substance was performed. Since the test item hydrolyses to methanol and a silanol hydrolysis product, methanol was analytically monitored at several timepoints in order to gather information on the hydrolysis rate of the test item. The produced amount of methanol reached to the theoretical amount already at the first measurement just after preparation of the solution, showing that the test item hydrolyzes rapidly.

Description of key information

Hydrolysis half-life: 6.9 h at 20-25°C and pH 7

Key value for chemical safety assessment

Half-life for hydrolysis:

6.9 h

Additional information

A preliminary test on the hydrolysis of the substance was performed within the frame of the biodegradation test according to national guideline standards and GLP. The hydrolysis test was performed in purified water with the duration of 2 h. The test item hydrolyses to methanol and the respective silanol hydrolysis product. Methanol was analytically monitored at time points 0, 0.5, 1 and 2 h and room temperature by GC in order to gather information on the hydrolysis rate of the test item. Based on the analytically measured emerged methanol, the test item was hydrolyzed right after the preparation of the solution at time point 0 (96% measured methanol compared to the theoretical amount in the substance).

Furthermore a preliminary hydrolysis test was conducted within the purposes of the environmental toxicity studies. The hydrolysis test was performed in purified water. It was considered that hydrolysis was completed when theoretical formed concentration of the methanol was detected. Methanol was analytically monitored at time points 0, 0.5, 1 and 2 h and the test was performed at room temperature. Based on the analytically measured emerged methanol, the test item was almost completely hydrolyzed right after the preparation of the solution at time point 0. 94.3% methanol was measured right after preparation of the solution and 102% methanol was measured after 2 h.

Furthermore a half-life value of 6.9 h at 20 - 25°C and pH 7 was obtained using an accepted validated QSAR method (Peter Fisk Associates, 2012).

The QSAR method was developed by Peter Fisk Associates (2012) and predicts half-lives at 20 -25°C of 0.3 h at pH 4 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.

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. 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 (Peter Fisk Associates 2012a).

Therefore, at low pH:

k_obs˜k_H3O+[H₃O⁺]

At pH 4 [H₃O⁺]=10^-4mol dm^-3and at pH 2 [H₃O⁺]=10^-2mol dm^-3; therefore, k_obsat pH 2 should be approximately 100 times greater than k_obsat 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 bis(trimethoxysilylpropyl) amine at pH 2 is 0.003 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 for bis(trimethoxysilylpropyl)amine 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 bis(trimethoxysilylpropyl)amine the 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.

The hydrolysis products are bis(trihydroxysilylpropyl)amine and methanol.

In conclusion all data reveal in a weight of evidence approach a fast hydrolysis of the substance. Based on the experimental data retrieved in preliminary tests of biodegradation and environmental toxicity studies, the substance hydrolyses rapidly in water and its half-life is less than the trigger value of 1 h given by the guidelines. However since no pH is mentioned in these preliminary tests the t1/2 = 6.9 h at pH from the QSAR results is used as key value.