(3-chloropropyl)triethoxysilane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-08-15 to 2007-11-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

April 13, 2004

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Version / remarks:

December 1992

Principles of method if other than guideline:

The test item was dissolved in an aqueous solution at a specific pH value (pH 4.0, pH 7.0 and pH 9.0) and was incubated at a specific temperature with a maximum deviation of ±0.5 °C and then kept constant within ±0.1 °C. The concentration of the test items was determined as a function of time, using a suitable analytical method. In case of decreasing concentrations, the logarithms of the concentrations are plotted against time (log10(ct)). If the plot is a straight line, the reaction is considered to be of (pseudo-) first order. The rate constant and the half life-live time was then calculated using the slope. Otherwise, the rate constant can be estimated by the use of the Arrhenius relationship.

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Sample Preparation
Before and after incubation at the relevant temperature, 1mL aliquot of the test solutions at each pH were added to 2mL of acetonitrile. After filtration (0.45 µm Nylon) 1 µl aliquots were analysed by measuring the FID signal of (3-chloropropyl)triethoxysilane after GC separation of the injected sample solution.

Buffers:

Buffer pH4, Biphthalate: Art. No. 5657
Buffer pH7, Phosphate: Art. No. 5656
Buffer pH9, Borate: Art. No. 7145

Filter Nylon (0.2µm): BGB Art. No.F2503-1
Filter Nylon (0.45 µm): BGB Art. No.F2503-2

The buffer solutions were sterilized for 25 minutes in an autoclave prior to first use. Nitrogen was passed through the buffer solutions for at least 1 minute except when freshly sterilized.

Details on test conditions:

Reagent:
Acetone: Art. No. 9254
Water: from Milli-Q supply
Filter Nylon (0.2µm): BGB Art. No.F2503-1
Filter Nylon (0.45 µm): BGB Art. No.F2503-2
The buffer solutions were sterilized for 25 minutes in an autoclave prior to first use. Nitrogen was passed through the buffer solutions for at least 1 minute except when freshly sterilized.

Equipment:
Glassware
All glassware, which must be inert in the pH range applied, was rinsed with sterile buffer. The hydrolysis was carried out in flasks, which were stoppered or sealed with an inert material (e.g. glass).

The test vessels were labelled accordingly.

Balances: Mettler XP205DR, AX205DR
GC Equpment
pH meter: Metrohm 692 with electrode Metrohm 6.0258.000
Water baths: Thermostically controlled water baths. Julabo F34, SW2 and SW22-2. Infors Aquatron

Principle of the test:
The test item was dissolved in an aqueous solution at a specific pH-value (pH 4, 7 and 9) and was incubated at a specific temperature with a maximum deviation of ±0.5°C and then kept constant within ±0.1°C. The concentration of the test item was determined as a function of time, using suitable analytical method.

Performance of the test:
General procedure:
According to the guidance, a preliminary hydrolysis tests was performed at 50±0.1°C at pH 4, 7 and 9 each.

Aliquots of each test solution were analysed at the beginning and after 2.4 hours and 120 hours using the analytical condition described above.

Duration:

2.4 h

pH:

4

Temp.:

50 °C

Duration:

120 h

pH:

7

Temp.:

25 °C

Duration:

120 h

pH:

9

Temp.:

25 °C

Number of replicates:

Duplicate

Positive controls:

no

Negative controls:

no

Preliminary study:

pH 4
The results of pH4.0 showed a significant degradation of (3-chloropropyl)triethoxysilane at 50.0°C. The test was repeated with two samples at pH 4.0 and 20°C. After 25 min and 23 mins of incubation at 20°C at least 86% of the test item was hydrolysed. Therefore, no main test according to the guideline could be performed. The half –life time was evaluated from the time between the sample preparation and the GC measurement.

pH 7
The results of the preliminary test show, that (3-chloropropyl)triethoxysilane is not stable at pH 7.0. Therefore further tests at 30°C, 40°C, and 60°C were performed.

pH 9
The results of the preliminary test show, that (3-chloropropyl)triethoxysilane is not stable at pH 9.0. Therefore further tests at 10°C, 20°C, and 30°C were performed.

Transformation products:

yes

Remarks:

The transformation products were not determined as part of this study, however, the hydrolysis products are (3-chloropropyl)silanetriol and ethanol

No.:

#1

No.:

#2

Key result

pH:

4

Temp.:

20 °C

DT50:

< 0.4 h

Type:

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

Remarks on result:

other: The test item was very unstable at pH 4

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.02 s-1

DT50:

35 h

Type:

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

Key result

pH:

7

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

23 h

Type:

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

Key result

pH:

7

Temp.:

40 °C

Hydrolysis rate constant:

0 s-1

DT50:

12 h

Type:

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

Key result

pH:

7

Temp.:

60 °C

Hydrolysis rate constant:

0 s-1

DT50:

3 h

Type:

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

Key result

pH:

9

Temp.:

10 °C

Hydrolysis rate constant:

0 s-1

DT50:

7 h

Type:

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

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0 s-1

DT50:

3 h

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0 s-1

DT50:

2 h

Type:

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

Key result

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

1.2 h

Type:

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

Details on results:

(3-chloropropyl)triethoxysilane is very unstable at pH 4.0. The half life time at 20°C is shorter than 24 minutes.
(3-chloropropyl)triethoxysilane at pH 7.0 has half life time of 35 hours at 25°C.
(3-chloropropyl)triethoxysilane at pH 9.0 has half life time of 2 hours at 25°C.

Hydrolysis at 50°C

The concentrations of the test item found in the test solutions before and after incubation times of 2.4 hours and 5 days are given in the table below.

Results according to the preliminary test

	0 hours	2.4 hours	2.4 hours	5 days	5 days
	Initial concentration measured [µg/mL]	Concentration measured [µg/mL]	Hydrolysis reaction	Concentration measured [µg/mL]	Hydrolysis reaction
pH 4	27.770	0	100	0	100
pH 4	14.981	0	100	0	100
pH 7	120.495	46.927	61	0	100
pH 7	94.099	51.404	45	0	100
pH 9	190.415	1.096	99	0	100
pH 9	363.387	4.229	99	0	100

pH 4

The results of the pH 4 showed significant degradation of the test item at 50°C. The test was repeated with two samples at pH 4 and 20°C. After 25 mins and 23 mins of incubation at 20°C, at least 86% of the test item was hydrolysed. Therefore, no main test was performed. The half-life was evaluated from the time between the sample preparation and the GC measurement.

Sample 1	Sample 1	Sample 1	Sample 2	Sample 2	Sample 2
Time [hours]	Concentration measured [µg/mL]	Hydrolysis [%]	Time [hours]	Concentration measured [µg/mL]	Hydrolysis [%]
0.00	79.3	0	0.00	152.0	0
0.38*	10.9	86	0.42**	6.4	96
0.77	8.9	89	0.80	4.2	97

*0.38 hours = 23 minutes

**0.42 hours = 25 minutes

 

pH 7

The results of the preliminary test showed that the test item was not stable at pH 7. Therefore, further tests at 30°C, 40°C and 60°C were performed.

pH 9

The results of the preliminary test showed that the test item was not stable at pH 9. Therefore, further tests at 10°C, 20°C and 30°C were performed.

 

Hydrolysis at pH 7 and different temperatures

Calculation of half-life time

The hydrolysis reaction at pH 7 is relatively fast. Therefore, further hydrolysis tests were performed at 30°C, 40°C and 60°C, each in duplicate. Each buffered test solution was analysed in time intervals.

The results are in the tables below.

Hydrolysis result at pH 7 and 30°C

Time [hours]	Sample 1	Sample 1	Sample 2	Sample 2
	Concentration measured [µg/mL]	Hydrolysis [%]	Concentration measured [µg/mL]	Hydrolysis [%]
0.0	110.3	0	124.8	0
5.9	94.5	14	114.4	8
7.5	93.7	15	115.6	7
23.4	63.8	42	74.2	41
25.1	60.7	45	79.5	36
25.9	61.7	44	75.4	40
26.8	53.1	52	64.1	49
27.6	54.0	51	68.7	45
28.5	49.9	55	60.8	51
29.3	58.2	47	62.3	50
30.1	51.4	53	61.8	51
30.9	48.3	56	60.6	51
31.8	49.4	55	56.6	55

 

 

Hydrolysis result at pH 7 and 40°C

Time [hours]	Sample 1	Sample 1	Sample 2	Sample 2
	Concentration measured [µg/mL]	Hydrolysis [%]	Concentration measured [µg/mL]	Hydrolysis [%]
0.0	115.4	0	118.4	0
2.0	97.7	15	100.1	15
2.8	93.4	19	93.8	21
3.5	86.6	25	92.6	22
4.3	93.8	19	89.9	24
4.9	86.0	25	91.4	23
20.0	37.1	68	37.0	69
20.8	35.7	69	35.2	70
21.5	32.8	72	34.0	71
22.3	31.6	73	31.6	73
23.0	31.2	73	31.3	74
23.8	29.7	74	29.4	75

 

Hydrolysis result at pH 7 and 60°C

Time [hours]	Sample 1	Sample 1	Sample 2	Sample 2
	Concentration measured [µg/mL]	Hydrolysis [%]	Concentration measured [µg/mL]	Hydrolysis [%]
0.0	273.4	0	110.0	0
1.1	153.3	44	94.7	14
1.9	131.2	52	73.2	33
2.6	117.4	57	60.4	45
3.4	102.6	62	51.4	53
4.1	87.3	68	44.0	60
4.9	72.8	73	35.1	68
5.6	54.3	80	30.2	73
6.4	50.1	82	23.8	78
7.1	38.0	86	19.6	82
7.9	32.4	88	16.4	85
8.6	26.7	90	14.8	87

 

The first order rate constant and half-life were calculated from where degradation is between 10% and 90%.

The reaction rate constant, k was calculated for all three temperatures by regression analysis.

The half-life time at pH 7 and 30°C was calculated to be 23 hours

The half-life time at pH 7 and 40°C was calculated to be 12 hours

The half-life time at pH 7 and 60°C was calculated to be 3 hours

 

Evaluation of the half-life time at 25°C

The calculated results of the activation energy and the k25 value (at 25°C) for pH 7 are summarised in the table below.

Calculation of the 1^st order rate constant of the hydrolysis reaction at pH 7 according to Arrhenius equation is reported in the table below

Temp [°C]	k [1/hours]	E [kJ/mol]	k at 25°C [1/hours]	k at 25°C [1/s]	t1/2 at 25°C [days]	t1/2 at 25°C [hours]
30	2.59E-2	58.2	1.99E-2	5.53E-6	1.5	35
30	3.74E-2
40	5.54E-2
40	5.65E-2
60	2.37E-1
60	2.48E-1

 

m aus Ahrr. -7000.813732

b aus Ahrr. 19.56450141

 

Hydrolysis at pH 9 and different temperatures

Calculation of half-life time

The hydrolysis reaction at pH 9 is relatively fast. Therefore, further hydrolysis tests at pH 9 were performed at 10°C, 20°C and 30°C, each in duplicate. Each buffered test solution was analysed in time intervals.

The results are in the tables below.

Hydrolysis result at pH 9 and 10°C

Time [hours]	Sample 1	Sample 1	Time [hours]	Sample 2	Sample 2
	Concentration measured [µg/mL]	Hydrolysis [%]		Concentration measured [µg/mL]	Hydrolysis [%]
0.0	86.1	0	0.0	118.2	0
1.0	100.1	-16	1.1	135.9	-15
3.1	78.5	9	2.0	112.4	5
4.1	67.0	22	3.0	99.6	16
5.1	63.9	26	4.0	96.4	18
6.1	56.8	34	5.0	83.2	30
7.1	52.0	40	6.0	77.5	34
8.1	46.9	46	7.0	66.6	44
9.1	41.8	51	8.0	59.4	50
10.1	38.4	55	9.0	59.0	50
			10.0	54.5	54

 

Hydrolysis result at pH 9 and 20°C

Time [hours]	Sample 1	Sample 1	Time [hours]	Sample 2	Sample 2
	Concentration measured [µg/mL]	Hydrolysis [%]		Concentration measured [µg/mL]	Hydrolysis [%]
0.0	210.8	0	0.0	107.6	0
0.8	163.0	23	0.4	101.2	6
1.6	128.6	39	1.0	91.2	15
2.0	118.9	44	1.6	73.9	31
2.4	99.2	53	2.0	70.9	34
2.7	103.4	51	2.4	57.0	47
3.1	84.2	60	3.0	51.8	52
3.9	77.0	63	3.4	45.9	57
4.3	66.1	69	3.8	39.8	63
4.7	57.6	73	4.2	38.1	65
5.1	51.9	75	4.6	33.8	69
5.4	49.0	77	5.0	30.7	71
			5.4	27.5	74

 

Hydrolysis result at pH 9 and 30°C

Time [hours]	Sample 1	Sample 1	Time [hours]	Sample 2	Sample 2
	Concentration measured [µg/mL]	Hydrolysis [%]		Concentration measured [µg/mL]	Hydrolysis [%]
0.0	122.0	0	0.0	122.3	0
0.4	99.3	19	0.4	101.2	17
0.8	75.4	38	0.8	72.6	41
1.2	56.5	54	1.2	61.2	50
1.6	45.6	63	1.6	50.0	59
2.1	32.2	74	1.9	37.0	70
2.5	26.3	78	2.3	30.8	75
2.9	22.0	82	2.7	23.6	81
3.3	14.7	88	3.1	19.5	84
3.7	12.5	90	3.5	16.1	87
4.1	10.0	92	4.1	11.8	90

 

The reaction rate constant, k was calculated for all three temperatures by regression analysis.

The half-life time at pH 9 and 10°C was calculated to be 7 hours

The half-life time at pH 9 and 20°C was calculated to be 3 hours

The half-life time at pH 9 and 30°C was calculated to be 1.2 hours

 

Evaluation of the half-life time at 25°C

The calculated results of the activation energy and the k25 value (at 25°C) for pH 9 are summarised in the table below.

 

Calculation of the 1^st order rate constant of the hydrolysis reaction at pH 9 according to Arrhenius equation is reported in the table below

Temp [°C]	k [1/hours]	E [kJ/mol]	k at 25°C [1/hours]	k at 25°C [1/s]	t1/2 at 25°C [days]	t1/2 at 25°C [hours]
10	9.68E-2	66.0	3.97E-1	1.10E-4	0.1	2
10	9.32E-2
20	2.59E-1
20	2.69E-1
30	6.22E-1
30	5.48E-1

 

m aus Ahrr. -7934.098654

b aus Ahrr. 25.68832332

The results are summarised below (the value typed in italics and were calculated using the Arrthenius equation)

pH	Temperature	Reaction rate constant	Reaction rate constant	Half life time
7.0	25	5.53 *10^-6	1.99 * 10^-2	35
	30	3.32 * 10^-2 *	8.79 * 10^-6	23
	40	5.6 * 10^-2 *	1.55 *10^-5	12
	60	2.42 *10^-1 *	6.74 * 10^-5	3
9.0	25	3.97 *10^-1	1.10 *10^-4	2
	10	9.5 * 10^-2 *	2.64 * 10^-5	7
	20	2.63 *10^-1 *	7.33 * 10^-5	3
	30	6.02 *10^-1 *	1.67 *10^-4	1.2

* The tabulated value is the mean of two samples

The test substance is very unstable at pH4.0. Its half life time at 20°C is shorter than 24 minutes.

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis half-lives of <0.4 h at pH 4 and 20°C, 35 h at pH 7 and 2 hours at pH 9 and 25°C were determined for the substance in a reliable study conducted according to OECD test guideline 111 and EU test method C7, and in compliance with GLP.

Description of key information

Hydrolysis half-lives: <0.4 hours at pH 4 and 20°C, 35 hours at pH 7 and 2 hours at pH 9 and 25°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

35 h

at the temperature of:

25 °C

Additional information

The hydrolysis of the substance has been determined in accordance with OECD Test Guideline 111 and in compliance with GLP. Hydrolysis half-lives are reported below:

- At pH 4, half-life is <0.4 hours (<24 minutes) at 20°C

- At pH 7, half-lives are 35 hours at 25°C, 23 hours at 30°C, 12 hours at 40°C and 3 hours at 60°C

- At pH 9, half-lives are 7 hours at 10°C, 3 hours at 20°C, 2 hours at 25°C and 1.2 hours at 30°C

At pH 4, the hydrolysis half-life was estimated at 20°C because the test substance was hydrolytically unstable. At pH 8 and 25°C, the half-life has been estimated to be approximately 19 hours.

The result is considered to be reliable and is selected as key study.

As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at around 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.

 

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 the substance at pH 2 and 20°C is therefore approximately <0.004 hours (<14 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 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) * e^(0.08.(T-X))

 

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

 

Thus, for (3-chloropropyl)triethoxysilane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 13 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is 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 37.5°C is therefore approximately 5 seconds. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC.

 

The hydrolysis products in this case are (3-chloropropyl)silanetriol (1 mole) and ethanol (3 moles).

The hydrolysis half-lives of substances used for read across are discussed below.

Hydrolysis of the read-across substance (3-chloropropyl)trimethoxysilane (CAS 2530-87-2)

Data for the substance (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) are currently read-across to the submission substance (3-chloropropyl)triethoxysilane for the repeated dose toxicity: inhalation, toxicity to reproduction and developmental toxicity endpoints. The presence of common functional group (3-chloropropyl), and the formation of the same silanol hydrolysis product, (3-chloropropyl)silanetriol in the two substances are relevant for this read-across.

(3-Chloropropyl)trimethoxysilane has measured half-lives of <0.083 hours (<5 minutes) at pH 4 and 20°C, 4.5 hours at pH 7 and 20°C, 3.1 h at pH 7 and 25°C, 1.0 hour at pH 7 and 40°C and 0.51 hour at pH 7 and 50°C. At pH 9 and 25°C, the hydrolysis half-life is <0.1 hours. The study was conducted in accordance with OECD Test Guideline 111.At pH 4 and pH 9.

In a non-standard study (Gorman 1995), the disappearance of the methoxy groups was monitored by the use of ¹H-NMR; hydrolysis half-lives of 0.88 hours at pH 7 and 0.37 h at pH 9 and 25°C was determined for (3-chloropropyl)trimethoxysilane. In the supporting study, 3-chloropropyltrimethoxysilane was an impurity in another substance and the study was designed primarily to determine the half-life of the major constituent.

The half-lives at pH 2 and 20-25°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 approximately 3 seconds at pH 2 and 20-25°C. 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. At pH 7 and 37.5°C, the half-life is approximately 1.1 hour. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately 5 seconds. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half -life will be in between the half-lives at pH 4 and pH 7 at 37.5ºC.

The hydrolysis products in this case are (3-chloropropyl)silanetriol (1 mole) and methanol (3 moles).