Triethoxy(3-thiocyanatopropyl)silane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-12-19 to 2012-03-19

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 31 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

The concentration of the test substance in the test samples was determined immediately after preparation (t=0) and at several sampling points after t=0. The samples taken were cooled to room temperature using running tap water. Immediately after cooling, 4 ml of each sample was extracted with 4 ml hexane and analysed. The shaking time was 30 seconds.

Buffers:

- pH: 4
- Type and final molarity of buffer: Acetate buffer, 0.1 M
- Composition of buffer: 16.6% 0.1 M sodium acetate and 83.4% 0.1 M acetic acid. The buffer contains 0.0009% (w/v) sodium azide

- pH: 7
- Type and final molarity of buffer: Phosphate buffer, 0.1M
- Composition of buffer: 0.1 M potassium di-hydrogenphosphate adjusted to pH 7 using 10 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide

- pH: 9
- Type and final molarity of buffer: Borate buffer, 0.1 M
- Composition of buffer: 0.1 M boric acid and 0.1 M potassium chloride adjusted to pH 9 using 10 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide

Details on test conditions:

- Tier 2-Main study was performed at two (pH 4) or three different temperatures (pH 7 and 9).- The study at pH 4 was performed at 50°C and 21°C. Due to the quick hydrolysis at 21°C it was concluded that it is not possible to determine the hydrolysis rate accurately. Therefore no third temperature was tested.-To obtain sufficiently spaced data points, testing at 40°C at pH 7 and testing at 50°C at pH 9 was performed in two separate tests. The data of the two parts were combined to obtain accurate values for the hydrolysis rate. - The buffer solutions were filter-sterilised through a 0.2 µm filter and transferred into sterile vessels. - To exclude oxygen, nitrogen gas was purged through the solution for 5 minutes. - The test substance was spiked to the solutions at a target concentration of 7.4 mg/l. - For spiking, a solution of the test substance was prepared in acetone. - The spiking volume was < 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.- For each sampling time, duplicate sterile vessels under vacuum were filled with 6 ml test solution and placed in the dark in a temperature-controlled environment. -The pH of the test solutions at pH 4, 7 and 9 (except for the blanks) was determined at least at the beginning and at the end of the test.

Duration:

0.25 h

pH:

4

Initial conc. measured:

>= 3.96 - <= 4.33 mg/L

Duration:

0.33 h

pH:

4

Initial conc. measured:

>= 3.64 - <= 3.68 mg/L

Duration:

167 h

pH:

7

Initial conc. measured:

>= 7.48 - <= 7.77 mg/L

Duration:

26.5 h

pH:

7

Initial conc. measured:

>= 7.41 - <= 7.84 mg/L

Duration:

22.75 h

pH:

7

Initial conc. measured:

>= 6.28 - <= 6.39 mg/L

Duration:

4.33 h

pH:

9

Initial conc. measured:

>= 8.13 - <= 8.3 mg/L

Duration:

2.25 h

pH:

9

Initial conc. measured:

>= 6.82 - <= 7.29 mg/L

Duration:

0.55 h

pH:

9

Initial conc. measured:

>= 7.07 - <= 8.25 mg/L

Number of replicates:

Duplicates

Positive controls:

no

Negative controls:

yes

Remarks:

(no test substance was detected in the blank buffer solutions pH 4, 7 and 9)

Preliminary study:

The preliminary test was not performed since triethoxy(3-thiocyanatopropyl)silane was known to be hydrolytically unstable at pH 4, pH 7 and pH 9 (t0.5 25°C < 1 year).

Test performance:

RECOVERIES- Recovery: concentration analysed at t=0 relative to the nominal concentration. - Mean recovery (see table below): mean of duplicate test samples. - Acceptable range for non-labelled chemicals: 70-110%. - pH 4: The mean recoveries were below the range for non-labelled chemicals due to the quick hydrolysis of the test substance at pH 4. - pH 7: The mean recoveries fell within 70-110%; the analytical method was adequate to support the hydrolysis study on the test substance. - pH 9: The mean recoveries fell within the range of 90-110%; the analytical method was adequate to support the hydrolysis study on the test substance. HYDROLYSIS RATE: For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. Linear relationships were obtained at all temperatures. For pH 7 and 9, the half-lifetimes of the 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. The rate constant and half-life time of the test substance at each temperature was obtained. The Arrhenius equation was used to determine the rate constant and half-life time at 25°C.For pH 4 and 21°C, the logarithms of the relative concentrations were correlated with time using linear regression analysis. No further calculations were performed.

Transformation products:

not measured

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

Research to investigate the identity or nature and rates of formation and decline of hydrolysis products was not required since the studies were conducted according to the testing guidelines provided in Annex VIII (volume 10-100 tons/year).

% Recovery:

56

pH:

4

Temp.:

20 °C

Duration:

>= 0 - <= 0.25 h

% Recovery:

49

pH:

4

Temp.:

50 °C

Duration:

>= 0 - <= 0.33 h

% Recovery:

103

pH:

7

Temp.:

20 °C

Duration:

>= 0 - <= 167 h

% Recovery:

>= 100 - <= 104

pH:

7

Temp.:

40 °C

Duration:

>= 0 - <= 26.5 h

% Recovery:

86

pH:

7

Temp.:

50 °C

Duration:

>= 0 - <= 22.75 h

% Recovery:

110

pH:

9

Temp.:

20 °C

Duration:

>= 0 - <= 4.3 h

% Recovery:

95

pH:

9

Temp.:

30 °C

Duration:

>= 0 - <= 2.25 h

% Recovery:

>= 97 - <= 110

pH:

9

Temp.:

50 °C

Duration:

>= 0 - <= 0.55 h

Key result

pH:

4

Temp.:

20 °C

DT50:

< 0.1 h

Type:

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

Remarks on result:

other: Rate constant was not determined due to fast hydrolysis rate

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.02 h-1

DT50:

35 h

Type:

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

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.03 h-1

DT50:

23 h

Type:

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

Key result

pH:

7

Temp.:

40 °C

Hydrolysis rate constant:

0.09 h-1

DT50:

7.7 h

Type:

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

Key result

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.198 h-1

DT50:

3.5 h

Type:

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

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.583 h-1

DT50:

1.2 h

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.834 h-1

DT50:

0.83 h

Type:

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

Key result

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

1.14 h-1

DT50:

0.61 h

Type:

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

Key result

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

5.58 h-1

DT50:

0.12 h

Type:

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

Details on results:

At pH 4, 20°C and 50°C, the mean recoveries of the buffer solutions did not fall within the recommended range for non-labelled chemicals of 70 - 110%. The lower recoveries are due to rapid hydrolysis of the test substance at these conditions.

Results at pH 4

Table 1: Main test: hydrolysis of the test substance at 20°C and pH4

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	3.96	96	1.98	4.0
0	4.33	104	2.02	4.0
0.08	1.75	42	1.62	4.0
0.08	1.73	42	1.62	4.0
0.17	0.910	22	1.34	4.0
0.17	0.819	20	1.30	4.0
0.25	0.404	9.7	0.99	4.0
0.25	0.415	10	1.00	4.0

 

Table 2: Main test: hydrolysis of the test substance at 50°C and pH4

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	3.64	99	2.00	4.0
0	3.68	101	2.00	4.0
0.17	n.d.
0.17	n.d.
0.33	n.d.			4.0
0.33	n.d.			4.0

n.d = not detected

Table 3: Recoveries at pH4

Temperature (°C)	Nominal concentration [mg/l]	Analysed concentration [mg/l]	Recovery [%]	Mean recovery [%]
20	7.44	3.96	53	56
20	7.44	4.33	58
50	7.41	3.64	49	49
50	7.41	3.68	50

 

Results at pH 7

Table 4: Main test: hydrolysis of the test substance at 20°C and pH7

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	7.48	98	1.99	7.0
0	7.77	102	2.01	7.0
7.00	5.88	77	1.89
7.00	6.21	81	1.91
23.00	4.56	60	1.78
23.00	4.55	60	1.78
30.00	4.00	52	1.72
30.00	3.98	52	1.72
46.50	2.79	37	1.56
46.50	2.80	37	1.56
71.00	1.61	21	1.33
71.00	1.63	21	1.33
78.00	1.60	21	1.32	7.0
78.00	1.66	22	1.34	7.0
101.50	0.894	12	1.07	7.0
101.50	0.956	13	1.10	7.0
167.00	0.245	3.2	0.51	7.0
167.00	0.277	3.6	0.56	7.0

 

Table 5: Main test – hydrolysis of the test substance at 40°C and pH 7 – part 1

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0.00	7.41	100	2.00	7.0
0.00	7.43	100	2.00	7.0
2.50	5.31	72	1.85
2.50	5.45	74	1.87
4.00	5.24	71	1.85
4.00	5.27	71	1.85
5.00	5.14	69	1.84
5.00	4.63	62	1.80
6.00	4.34	59	1.77
6.00	4.38	59	1.77
7.00	3.94	53	1.73
7.00	3.97	54	1.73
23.00	0.936	13	1.10
23.00	0.963	13	1.11
24.00	0.882	12	1.07	7.0
24.00	0.866	12	1.07	7.0
26.50	0.663	8.9	0.95	7.0
26.50	0.683	9.2	0.96	7.0

 

Table 6: Main test – hydrolysis of the test substance at 40°C and pH 7 – part 2

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	7.84	102	2.01	7.0
0	7.60	98	1.99	7.0
16.00	1.64	22	1.34
16.00	1.64	22	1.35
17.50	1.45	20	1.29
17.50	1.45	19	1.29
19.00	1.26	17	1.23	7.0
19.00	1.30	18	1.24	7.0

 

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

Sampling time [hours]	Analysed concentration [mg/]	Relative concentration [%]	Logarithm relative concentration	Actual pH
0	6.39	101	2.00	7.0
0	6.28	99	2.00	7.0
0.50	6.11	96	1.98
0.50	6.36	100	2.00
1.00	5.59	88	1.95
1.00	5.61	89	1.95
2.25	4.42	70	1.84
2.25	4.36	69	1.84
4.00	3.04	48	1.68
4.00	2.94	46	1.67
5.00	2.48	39	1.59
5.00	2.47	39	1.59
6.00	2.02	32	1.50
6.00	1.96	31	1.49
6.75	1.76	28	1.44
6.75	1.78	28	1.45
7.75	1.42	22	1.35	7.0
7.75	1.47	23	1.36	7.0
22.75	n.d.			7.1
22.75	n.d.			7.1

 

Table 8: Recoveries at pH 7

Temperature (°C)	Nominal concentration [mg/l]	Analysed concentration [mg/l]	Recovery [%]	Mean recovery [%]
20	7.44	7.48	101	103
20	7.44	7.77	104
40	7.44	7.41	100	100
40	7.44	7.43	100
40	7.44	7.84	105	104
40	7.44	7.60	102
50	7.41	6.39	86	86
50	7.41	6.28	85

 

Table 9: Statistical parameters of the regression curves at pH 7

Temperature (°C)	Slope [hours-1]	Intercept	Coefficient of correlation
20	-0.00869	1.98	0.998
40	-0.0391	1.99	0.998
50	-0.0861	2.02	0.998

 

Table 10:Rate constants (kobs) and half-life time (t½)at pH 7

Temperature [°C]	kobs [hours-1]	t½
20	0.0200	35 hours
25	0.0297	23 hours
40	0.0901	7.7 hours
50	0.198	3.5 hours

Validity criteria fulfilled:

yes

Conclusions:

A hydrolysis half-life of < 0.1 h at pH 4 and 20°C, 23 h at pH 7 and 25°C and 0.8 h at pH 9 and 25°C was determined for the substance in accordance with OECD 111 and in compliance with GLP. The result is considered reliable.

Description of key information

Hydrolysis: half-life < 0.1 h at pH 4 and 20°C, 23 h at pH 7 and 25°C, 0.8 h at pH 9 and 25°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

23 h

at the temperature of:

25 °C

Additional information

The hydrolysis potential of the registered substance has been measured in accordance with OECD Test Guideline 111 and in compliance with GLP. The hydrolysis half-lives are:

 

pH 4; < 0.1 h at 20°C (very rapid hydrolysis was observed at pH 4)

pH 7; 35 h at 20°C, 23 h at 25°C, 7.7 h at 40°C and 3.5 h at 50°C

pH 9; 1.2 h at 20°C, 0.83 h at 25°C, 0.61 h at 40°C and 0.12 h at 50°C

 

The study is considered to be reliable and has been assigned as key study.

 

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.

 

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 triethoxy(3-thiocyanatopropyl)silane (CAS 34708-08-2; EC No. 200-578-6) at pH 2 and 25°C 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 seconds. As a worst-case it can therefore be considered that the half-life of the submission 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 triethoxy(3-thiocyanatopropyl)silane the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is 8.5 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 to temperature to the limit value and the hydrolysis half-life is therefore approximately 5 seconds.

 

The hydrolysis products are (3-thiocyanatopropyl)silanetriol and ethanol (CAS 64-17-5; EC No. 200-578-6).