3-chloropropyltrimethoxysilane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-03-13 to 2014-04-04

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)

Deviations:

yes

Remarks:

(i) at pH 4 and 9, main study was performed at 25°C, due to instability of test substance (ii) mean accuracy of 0.3 mg/l was slightly below the criterion of 70-110% in the validation of analytical method

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

(i) at pH 4 and 9, main study was performed at 25°C, due to instability of test substance (ii) mean accuracy of 0.3 mg/l was slightly below the criterion of 70-110% in the validation of analytical method

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2110 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

(i) at pH 4 and 9, main study was performed at 25°C, due to instability of test substance (ii) mean accuracy of 0.3 mg/l was slightly below the criterion of 70-110% in the validation of analytical method

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

pH 4
Acetate buffer pH 4, 0.01 M: solution of 16.7% 0.01 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. The buffer contains 0.0009% (w/v) sodium azide.

pH 7
Phosphate buffer pH 7, 0.01 M: solution of 0.01 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

pH 9
Borate buffer pH 9, 0.01 M: solution of 0.01 M boric acid in water and 0.01 M potassium chloride in water adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Details on test conditions:

List of protocol deviations
- Due to the hydrolytically instability of the test substance at pH 4 and pH 9, the main (Tier 2) hydrolysis study was performed at 25°C. An estimation for pH 4 and pH 9 is the best approach to present the hydrolysis rate at 25°C which is comparable to environmental conditions.

- In the validation of an analytical method. the mean accuracy at 0.3 mg/l concentration level was slightly below the criterion of 70-110%. Though the coefficient of variation was ≤ 20% and the mean accuracy at 10 mg/l did meet the criterion. Since the rate of hydrolysis is determined as a relative value the analytical method was accepted for the analysis of the test substance in water in the target concentration range of 0.3 - 10 mg/l.

Duration:

23 d

Initial conc. measured:

10 mg/L

Number of replicates:

The study was performed in duplicates

Preliminary study:

The preliminary study was not performed since (3-chloropropyl)trimethoxysilane was known to be hydrolytically unstable at pH 4, pH 7 and pH 9 (half-life at 25°C= < 1 year).

Transformation products:

not measured

% Recovery:

ca. 4.5 - ca. 5.8

pH:

4

Temp.:

25 °C

Duration:

ca. 0 - ca. 0.33 h

% Recovery:

ca. 81 - ca. 85

pH:

7

Temp.:

20 °C

Duration:

ca. 0 - ca. 22.3 h

% Recovery:

ca. 91 - ca. 98

pH:

7

Temp.:

40 °C

Duration:

ca. 0 - ca. 20.7 h

% Recovery:

ca. 88 - ca. 93

pH:

7

Temp.:

50 °C

Duration:

ca. 0 - ca. 1.83 h

% Recovery:

ca. 20 - ca. 22

pH:

9

Temp.:

25 °C

Duration:

ca. 0 - ca. 0.33 h

Key result

pH:

4

Temp.:

25 °C

DT50:

< 0.083 h

Type:

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

Remarks on result:

other: The rate constant at pH 4 could not be determined due to the fast hydrolysis of the test substance

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.152 h-1

DT50:

4.5 h

Type:

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

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.224 h-1

DT50:

3.1 h

Type:

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

Remarks on result:

other: The half-life time at 25°C was calculated from the Arrhenius equation using the results at 20, 40 and 50°C

Key result

pH:

7

Temp.:

40 °C

Hydrolysis rate constant:

0.664 h-1

DT50:

1 h

Type:

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

Key result

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

1.36 h-1

DT50:

0.51 h

Type:

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

Key result

pH:

9

Temp.:

25 °C

DT50:

< 0.1 h

Type:

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

Remarks on result:

other: The rate constant at pH 9 could not be determined due to the fast hydrolysis of the test substance

Details on results:

The main study (Tier 2) was performed for the determination of the rate of hydrolysis of (3-chloropropyl)trimethoxysilane at pH values normally found in the environment (pH 4-9).

The half-lives at different pHs are summarised below:

pH 4 and 25°C = <5 minutes (<0.083 hour)
pH 7 and 20°C = 4.5 hours
pH 7 and 25°C = 3.1 hours
pH 7 and 40°C = 1.0 hour
pH 7 and 50°C = 0.51 hours
pH 9 and 25°C = <6 minutes (<0.1 h)

Main study Tier 2, pH 4:

The analytical results of the main study - Tier 2 performed at pH 4 are given in Table 1 and Table 2.

 

No test substance was detected in the blank buffer solutions.

 

The mean recovery of the buffer solutions did not meet the acceptable range for non-labelled chemicals of 70-110%. The mean recovery of the buffer solution pH 4 at 25°C was outside this range. The low recovery was caused by the fast hydrolysis of the test substance at pH 4.

Table 1: Main test – hydrolysis of the test substance at pH 4 and 25°C

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	0.453	88	1.94	4.0
0	0.579	112	2.05	4.0
0.083	<0.200	n.a.	n.a.	4.0
0.083	<0.200	n.a.	n.a.	4.0
0.17	<0.200	n.a.	n.a.	4.0
0.17	<0.200	n.a.	n.a.	4.0
0.25	<0.200	n.a.	n.a.	4.0
0.25	<0.200	n.a.	n.a.	4.0
0.33	<0.200	n.a.	n.a.	4.0
0.33	<0.200	n.a.	n.a.	4.0

Table 2: Recoveries (t= 0) at pH 4

Temperature (°C)	Nominal concentration [mg/l]	Analysed concentration [mg/l]	Recovery [%]	Mean recovery [%]
25	10	0.453	4.5	5.2
	10	0.579	5.8

 

In the chromatograms of the t=0 hour samples, 5.2% of nominal concentration was observed at the retention time of the test substance. In the chromatograms of the t=0.083 hours samples, no response was seen. Based on this, it was concluded that hydrolysis at 25°C is too quick to determine the half-life time accurately. The half-lifetime at pH 4 was determined to be <5 minutes, i.e. the time between spiking of the buffer pH 4 solution with test substance and time of sampling t=0 hours.

Main study Tier 2, pH 7:

The analytical results of the main study are given in Table 3 to Table 6.

 

No test substance was detected in the blank buffer solutions. The mean recoveries of the buffer solutions met the acceptable range for non-labelled chemicals of 70-110%.

Table 3: Main test – hydrolysis of the test substance at pH 7 and 20°C

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0.00	8.05	97	1.99	7.0
0.00	8.50	103	2.01	7.0
1.00	7.09	86	1.93
1.00	7.06	85	1.93
2.00	5.34	64	1.81
2.00	5.41	65	1.82
3.00	4.66	56	1.75
3.00	4.65	56	1.75
4.00	4.46	54	1.73
4.00	4.44	54	1.73
5.00	4.22	51	1.71
5.00	4.12	50	1.70
5.75	3.44	42	1.62	7.0
5.75	3.53	43	1.63	7.0
22.33	0.272	3.3	0.52	7.0
22.33	0.255	3.1	0.49	7.0

 

Table 4: Main test – hydrolysis of the test substance at pH 7 and 40°C

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0.00	9.05	96	1.98	7.0
0.00	9.84	104	2.02	7.0
0.25	7.90	84	1.92
0.25	8.12	86	1.93
0.83	5.94	63	1.80
0.83	5.66	60	1.78
1.25	4.31	46	1.66
1.25	4.35	46	1.66
1.75	3.07	32	1.51
1.75	3.24	34	1.54
2.00	2.69	28	1.45
2.00	2.67	28	1.45
2.33	1.98	21	1.32
2.33	2.08	22	1.34
2.83	1.41	15	1.17	7.0
2.83	1.50	16	1.20	7.0
3.33	0.992	11	1.02	7.0
3.33	1.09	12	1.06	7.0
20.7	<0.200	n.a.	n.a.	7.0
20.7	<0.200	n.a.	n.a.	7.0

 

Table 5: Main test – hydrolysis of the test substance at pH 7 and 50°C

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0.00	8.83	97	1.99	7.0
0.00	9.29	103	2.01	7.0
0.17	7.52	83	1.92
0.17	7.29	80	1.91
0.25	6.65	73	1.87
0.25	4.96	55	1.74
0.33	5.81	64	1.81
0.33	5.76	64	1.80
0.42	5.23	58	1.76
0.42	5.33	59	1.77
0.50	4.73	52	1.72
0.50	4.66	51	1.71
0.58	4.43	49	1.69
0.58	4.35	48	1.68
0.67	4.03	45	1.65
0.67	3.92	43	1.64
0.75	3.18	35	1.55
0.75	3.21	35	1.55
0.83	3.41	38	1.58
0.83	3.37	37	1.57
1.00	2.29	25	1.40	7.0
1.00	2.20	24	1.39	7.0
1.50	1.25	14	1.14	7.0
1.50	1.33	15	1.17	7.0
1.83	0.682	7.5	0.88	7.0
1.83	0.692	7.6	0.88	7.0

 

Table 6: Recoveries (t=0) at pH 7

Temperature (°C)	Nominal concentration [mg/l]	Analysed concentration [mg/l]	Recovery [%]	Mean recovery [%]
20	10	8.05	81	83
	10	8.50	85
40	10	9.05	91	94
	10	9.84	98
50	10	8.83	88	91
	10	9.29	93

 

For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. At all temperatures linear relationships were obtained using all individual results.

 

The half-life times of the test substance were determined according to the model for pseudo-first order reactions. All logarithms of the relative concentrations were correlated with time using linear regression analysis since the coefficient of correlation (r) was >0.99. Figure 4 (attached) illustrates the regression curves and Table 7 shows the statistical parameters.

 

Table 7: Statistical parameters of the regression curves

Temperature (°C)	Slope [hours^-1]	Intercept	Coefficient of correlation
20	-6.62x10^-2	1.99	0.997
40	-2.88x10^-1	2.01	0.998
50	-5.90x10^-1	2.01	0.992

 

The rate constant (k_obs) and half-life time of the test substance at each temperature was obtained and the Arrhenius equation (i.e E/R-6.88x10³ and ln A 21.6) was used to determine the rate constant and half-life time at 25°C (see Table 8).

Table 8: Rate constants (k_obs) and half-life time (t_½)

Temperature [°C]	kobs [hours^-1]	t½
20	1.52x10^-1	4.5 hours
25	2.24x10^-1	3.1 hours
40	6.64x10^-1	1.0 hours
50	1.36x10^0	0.51 hours

Main study Tier 2, pH 9:

The analytical results of the main study are given in Table 9 to Table 10.

 

No test substance was detected in the blank buffer solutions.

 

The mean recoveries of the buffer solutions did not meet the acceptable range for non-labelled chemicals of 70-110%. The mean recoveries of the buffer solutions in the test at 25°C were outside this range. The lower recoveries are caused by the fast hydrolysis of the test substance at pH 9.

Table 9: Main test – hydrolysis of the test substance at pH 9 and 25°C

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	2.21	105	2.02	9.0
0	2.01	95	1.98	9.0
0.083	0.524	25	1.40	9.0
0.083	0.516	24	1.39	9.0
0.17	0.219	10	1.02	9.0
0.17	0.248	12	1.07	9.0
0.25	<0.200	n.a.	n.a.	9.0
0.25	<0.200	n.a.	n.a.	9.0
0.33	<0.200	n.a.	n.a.	9.0
0.33	<0.200	n.a.	n.a.	9.0

 

Table 10: Recoveries (t=0) at pH 9

Temperature (°C)	Nominal concentration [mg/l]	Analysed concentration [mg/l]	Recovery [%]	Mean recovery [%]
25	10	2.21	22	21
	10	2.01	20

 

In the chromatograms of the t=0 hour samples, 21% of nominal concentration was observed at the retention time of the test substance. In the chromatograms of the t=0.083 hours samples, 24-25% relative concentration was seen. Based on this, it was concluded that hydrolysisat 25°C is too quick to determine the half-life time accurately. The half-lifetime at pH 9 was determined to be <6 minutes i.e. the time between spiking of the buffer pH4 solution with test substance and time of sampling t=0 hours.

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis half-lives of <0.083 h at pH 4, 3.1 h at pH 7 and <0.1 h at pH 9 and 25°C were determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP. The result is considered reliable.

Description of key information

Hydrolysis half-lives: <0.083 h at pH 4 and <0.1 h at pH 9 and 25°C. At pH 7, half-lives are 4.5 h at 20°C, 3.1 h at 25°C, 1.0 h at 40°C and 0.51 h at 50°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

3.1 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 (Schaap 2014). Hydrolysis half-lives are reported below:

- At pH 4, half-life is <0.083 h (<5 minutes) at 25°C

- At pH 9, half-life is <0.1 h at 25°C

- At pH 7, half-lives are 4.5 h at 20°C, 3.1 h at 25°C, 1.0 h at 40°C and 0.51 h at 50°C

At pH 4 and pH 9, the hydrolysis half-lives were estimated at 25°C because the test substance was hydrolytically unstable. The result is considered to be reliable and is selected as key study.

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

The key study was selected as:

- The study most recently conducted (Schaap 2014)

- The study that used the submission substance as the test material

- The study with the highest reliability

- The study conducted according to a relevant test guideline (OECD 111)

The available data are in agreement that the substance undergoes rapid hydrolytic degradation in contact with water.

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 25°C is therefore approximately 3 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)trimethoxysilane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 1.1 hours. 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. 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 and methanol.