3-(triethoxysilyl)propanethiol

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-07-02 to 2019-09-07

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:

2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Type and Frequency of Measurements:
Samples were taken at test start (0 h) and at 8 - 10 spaced points, normally between 10 and at least 75% of hydrolysis (e.g. 2 half lives). For details please see section 7.3.
The incubation temperature was checked automatically every minute for samples at pH 4, once in an hour for samples at 7 and 9 and at least once per day manually.

Buffers:

Buffer solutions with pH values 4, 7 and 9.

Buffer solutions were prepared from chemicals with analytical grade or better quality following the composition guidance given in “KÜSTER-THIEL, Rechentafeln für die Chemische Analytik” and the OECD Guideline No. 111, respectively, by direct weighing of the buffer components (nominal values are given below). Buffers were purged with nitrogen for 5 min and then the pH was checked to a precision of at least 0.1 at the test temperatures. Buffers were sterilized by filtration through 0.2 μm.

Buffer solution pH 4:
0.18 g of sodium hydroxide and 5.7555 g of mono potassium citrate were dissolved in 500 mL ultrapure water.

Buffer solution pH 7:
3.854 g of ammonium acetate were dissolved in 500 mL ultrapure water.

Buffer solution pH 9:
0.426 g sodium hydroxide, 1.8638 g potassium chloride and 1.5458 g boric acid were dissolved in 500 mL ultrapure water.

Additionally higher volumes of buffer solutions were prepared. The weighed portions of the chemicals were adapted.

Buffer details:
Chemical Origin Batch number Purity [%]
NaOH VWR 17F284110 ≥ 97
H3BO3 ROTH 028261978 ≥ 99.5
KCl ROTH 079279869 ≥ 99.5
Ammonium acetate VWR 18C204114 99.2
KH2 Citrate SIGMA-ALDRICH BCBW9888 ≥ 98
Ultrapure water MERCK In-house device

Details on test conditions:

Test container (sterile): Headspace vials, volume: 21 mL
Test volume: 10 mL
Stock solution: 10000 mg/L
Test concentration / solution: 40 mg/L

Application:
The test solutions were prepared at test start via stock solution. The test item was dissolved in MTBE and diluted with MTBE to a concentration of 4000 mg/L. 9.9 mL of sterile buffer solution were spiked with 0.1 mL of the dilution inside the test containers.

After the vials were sealed, they were transferred into the thermostat. The time between test item application and transfer to thermostat / analysis did not exceed 30 min, except at pH 7 (32 min).

Incubation times: The longest incubation time was 144 h, corresponding to 6 d.

Definitive test:
pH 4, 20, 30, 50°C: 2019-07-03 to 2019-08-28
pH 4, 10°C: 2019-08-28
pH 4, 20°C: 2019-08-29
pH 4, 30°C: 2019-08-30
pH 7, 20°C: 2019-07-02 to 2019-07-08
pH 7, 30°C: 2019-07-02 to 2019-07-05
pH 7, 50°C: 2019-07-02 to 2019-07-03
pH 9, 50°C: 2019-08-28
pH 9, 20, 30°C: 2019-08-27 to 2019-08-28

Temperature:
50 ± 0.5°C for the preliminary test;
10, 20 and 30 ± 0.5°C for the definitive test for pH 4;
20, 30 and 50 ± 0.5°C for the definitive test for pH 7 and 9

Light: Photolytic effects were avoided by using opaque water baths.

Sterility:
The sterility of the test solutions was checked at test end by colony forming units (CFU)-determination with Water Plate Count Agar from additional samples of the definitive test by incubation at 36 ± 1°C for 48 ± 4 h and at 22 ± 1°C for 72 ± 4 h.

Equipment:
Autoclave, 25-2-2, KSG STERILISATOREN GMBH
Balances, SARTORIUS and KERN
Clean bench, NUNC
Incubator, HERAEUS
Multipette Xstream, Eppendorf
pH-Meter, Lab850, SI ANALYTICS
Pipette, THERMO SCIENTIFIC
Sterile vacuum filtration system 0.2 μm, VWR
Thermometers, GMH 3750 and temperature sensing devices,
GREISINGER ELECTRONIC
Thermostats, LAUDA
Standard laboratory equipment

Duration:

1 d

pH:

4

Temp.:

20 °C

Duration:

6 d

pH:

7

Temp.:

20 °C

Duration:

2 d

pH:

9

Temp.:

20 °C

Number of replicates:

Duplicates per pH and sampling date, single injections

Positive controls:

no

Negative controls:

no

Statistical methods:

All data were computer generated and rounded for presentation from the full derived data. Consequently, if calculated manually based on the reported data minor deviations may occur from these figures. Calculations were carried out using software:
- Excel, MICROSOFT CORPORATION
- GraphPad Prism, GRAPHPAD SOFTWARE, INC

Preliminary study:

The preliminary test was conducted with a test item concentration of 40 mg/L in buffer solutions at pH 4, 7 and 9 at 50 °C. For all pH-values, the definitive test was performed, as a significant reduction (> 10%) of the test item concentration was observed in the preliminary test.

Transformation products:

not specified

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

Transformation Products (nonGLP):
From the test item structure Transformation products including diethoxy-, monoethoxy- and (3‐sulfanylpropyl)silanol, plus possible condensation products of these molecules, can be postulated. Correspondingly preliminary GC-MS scans were performed to clarify whether these or related molecules are detectable.

Therefore an analytical GC-MS full scan method for qualitative analyses was implemented under non-GLP on a TG-5 MS analytical column using the test item for comparison before and after derivatization with MSTFA.


Non-GLP Analytical Method for Transformation Products:
GC-MS/MS system: AGILENT-CHRONECT compiled of
Gaschromaptograph: 7890B, AGILENT
Autosampler: CHRONECT Robotic RTC PAL, AXEL SEMRAU
Detector: 7010 Quadrupol-MS/MS, AGILENT
Analytical column: TG-5 SIL MS, 30 m x 0.25 mm x 0.25 μm, THERMO SCIENTIFIC
Analytical Liner: Optic Frit Liner, desactivated, AGILENT
Software: MassHunter B 07, AGILENT Chronos 4.9.2-beta.11, AXEL SEMRAU Evolution Workstation 4.6.3, GL SCIENCES
Reagents: N-Methyl-N-trimethylsilyl-trifluoroacetamid (MSTFA), MERCK, for derivatization
Analytical standard: The test item was used as external standard.

Conditions of Analysis:
Injector temperature: splitless: 60 - 260 °C (heating rate 2 °C / s)
derivatised samples: isotherm (260 °C)
Split ratio: splitless / derivatised samples: split ratio 20
Injection volume: 1 μL (liquid)
Carrier gas: Ramped Pressure equaling a constant flow of approximately 2 mL/min

Temperature program:

Temperature [°C] Heating rate [°C/min] Hold time [min]
60 - 3.0
320 15 3.0

Conditions of Detection:
Conditions of detection:
Source Temperature 250°C; Ionization mode Electron impact ionization (EI)
Scan method MS Scan
Scan range m/z 40 -> 350

Preparation of the test sample: The dried organic layers of the samples prepared within the main test (pH 4, 30°C) were analyzed directly. Two samples were further derivatized with MSTFA before analyzes.
Derivatization 500 μL sample were added with 50 μL MSTFA and were incubated at 60°C for 30 min.

Results Transformation Products:
A MS full scan of one extracted replicate of the stored samples of each sampling point at pH4, 30°C gave beside of the main component only minor signals. These signals changed within the time elapsed of the test but a relation between time and concentration could not be demonstrated. Identification was proceeded with a NIST data base, but classification was not unambiguous.

Exemplarily two samples (samples of pH 4, 30°C, at test start and end, respectively) were further derivatized with MSTFA and analysed. These measurements gave similar results, no major signals except of the test item were identified. Therefore the absence of measurable signals indicates the absence of detectable transformation products.

Key result

pH:

4

Temp.:

10 °C

Hydrolysis rate constant:

0.001 s-1

DT50:

9.61 min

Type:

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

Remarks on result:

other: Confidence interval = 8.17 to 11.0 minutes

Key result

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0.004 s-1

DT50:

3.2 min

Type:

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

Remarks on result:

other: Confidence interval = 2.72 to 3.73 minutes

Key result

pH:

4

Temp.:

30 °C

Hydrolysis rate constant:

0.006 s-1

DT50:

1.86 min

Type:

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

Remarks on result:

other: Confidence interval = 1.23 to 2.47 minutes

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0 s-1

DT50:

32.1 h

Type:

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

Remarks on result:

other: Confidence interval = 30.7 to 33.5 hours

Key result

pH:

7

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

15.1 h

Type:

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

Remarks on result:

other: Confidence interval = 14.0 to 16.3 hours

Key result

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0 s-1

DT50:

3.55 h

Type:

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

Remarks on result:

other: Confidence interval = 3.34 to 3.75 hours

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0 s-1

DT50:

4.69 h

Type:

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

Remarks on result:

other: Confidence interval = 3.64 to 5.73 hours

Key result

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

3.58 h

Type:

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

Remarks on result:

other: Confidence interval = 2.25 to 5.20 hours

Key result

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.001 s-1

DT50:

0.316 h

Type:

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

Remarks on result:

other: Confidence interval = 0.175 to 0.433 hours

Other kinetic parameters:

Kinetics Considerations:
For all test conditions the ln concentration vs. time plots have regression graphs with slopes significantly non zero. First order reaction kinetics was applied for data computation. A confirmation of pseudo first order reaction kinetics with coefficients of determination > 0.8 was achieved for each test condition except for 30°C at pH 9. Nevertheless, based on the obtained data the pseudo first order reaction kinetics was deemed to be the best fit model for computation of kinetics data

Details on results:

The test item showed a moderate hydrolysis rate (2.4 h ≤ t1/2 ≤ 30 d) for pH 7 at 20, 30 and 50°C and for pH 9 at 20 and 30°C; and a fast hydrolysis (t1/2 ≤ 2.4 h) for pH 4 at 10, 20 and 30°C and for pH 9 at 50°C.

Results with reference substance:

No reference substance was used during the study because this is not required

Check of the pH-Value:

pH-Value of the Test System:

measured before application

pH-value	Measured pH-value
	at 10°C	at 20°C	at 30°C	at 40°C
4.0 ± 0.1	4.001	4.009	4.011	-
7.0 ± 0.1	-	6.904	6.907	6.911
9.0 ± 0.1	-	8.984	8.991	9.003

 

Temperature Monitoring:

Temperature of the Test System

measured every hour for pH 7 and 9 as well as every minute for pH 4

pH	Intended Temperature	Measured Temperature Mean ± SD	Measured Temperature Min. / Max.
4	10.0 ± 0.5 20.0 ± 0.5 30.0 ± 0.5	10.0 ± 0.09 20.0 ± 0.07 30.1 ± 0.06	9.9 / 10.2 19.9 / 20.2 29.9 / 30.2
7	20.0 ± 0.5 30.0 ± 0.5 50.0 ± 0.5	20.1 ± 0.05 30.0 ± 0.03 50.0 ± 0.03	20.0 / 20.2 29.9 / 30.1 49.9 / 50.0
9	20.0 ± 0.5 30.0 ± 0.5 50.0 ± 0.5	20.1 ± 0.03 30.2 ± 0.06 50.1 ± 0.01	20.0 / 20.1 29.9 / 30.2 50.1 / 50.1

SD = Standard deviation

The additional manually taken values confirm the results of the automated temperature recording of the datalogger.

Sterility:

As transformation occurs the sterility of the test solutions was checked at test end by colony forming units (CFU)-determination with Water Plate Count Agar from additional samples of the definitive test by incubation at 36 ± 1 °C for 48 ± 4 h and at 22 ± 1 °C for 72 ± 4 h.

No colony forming units could be determined. Therefore, sterility was given for all test solutions.

Hydrolysis Results:

Hydrolysis Results for the Test Item at pH 4 and 10°C

Hydrolysis Time [min]	Concentration [mg/L]	Ln Concentration
0.00	41.7	3.73
1.00	35.6	3.57
3.02	32.1	3.47
5.23	26.0	3.26
9.13	16.4	2.80
12.3	15.6	2.75
18.4	8.94	2.19
25.9	5.12	1.63
35.1	2.34	0.848
45.8	1.34	0.292
61.2	0.539	-0.619

 

Hydrolysis Results for the Test Item at pH 4 and 20°C

Hydrolysis Time [min]	Concentration [mg/L]	Ln Concentration
0.00	41.6	3.73
0.517	41.5	3.73
1.03	37.0	3.61
1.53	24.9	3.21
2.02	25.1	3.22
3.00	17.6	2.87
4.02	17.2	2.84
5.02	12.7	2.54
7.05	10.1	2.31
9.05
12.3

* Deemed to be outlier (no logical values); not taken into further accounts

Hydrolysis Results for the Test Item at pH 4 and 30°C

Hydrolysis Time [min]	Concentration [mg/L]	Ln Concentration
0.00	26.5	3.28
0.550	25.5	3.24
0.767	35.5	3.57
1.02	37.6	3.63
1.27	37.3	3.62
1.50	15.8	2.76
2.02	18.0	2.89
2.52
3.02	11.3	2.43
4.03	9.42	2.24
5.08	5.14	1.64

* Deemed to be an outlier (significantly outside the 95% confidence interval); not taken into further accounts

Hydrolysis Results for the Test Item at pH 7 and 20°C

Hydrolysis Time [h]	Concentration [mg/L]	Ln Concentration
0.00	37.9	3.63
0.833	36.1	3.58
2.27	36.0	3.58
4.88	31.4	3.45
7.43	34.4	3.54
21.5	24.3	3.19
30.1	18.6	2.93
47.4	13.6	2.61
51.1	12.9	2.56
71.1	7.75	2.05
144	1.68	0.521

 

Hydrolysis Results for the Test Item at pH 7 and 30°C

Hydrolysis Time [h]	Concentration [mg/L]	Ln Concentration
0.00	37.9	3.63
0.833	36.4	3.59
1.42	36.0	3.58
2.27	37.0	3.61
4.88	33.7	3.52
7.43	24.6	3.20
9.17	30.0	3.40
21.5	15.2	2.72
30.1	10.0	2.30
47.4	4.39	1.48
71.6	1.48	0.391

 

Hydrolysis Results for the Test Item at pH 7 and 50°C

Hydrolysis Time [h]	Concentration [mg/L]	Ln Concentration
0.00	37.9	3.63
0.833	34.3	3.53
1.20	31.6	3.45
1.75	31.5	3.45
2.27	26.6	3.28
3.68	18.9	2.94
4.88	16.9	2.94
6.02	12.6	2.53
7.43	9.26	2.23
9.17	6.65	2.89
21.5	0.117*	2.15*

* Value below the LOQ; not taken into further accounts

Hydrolysis Results for the Test Item at pH 9 and 20°C

Hydrolysis Time [h]	Concentration [mg/L]	Ln Concentration
0.00	30.6	3.42
0.517	30.9	3.43
1.03	36.9	3.61
1.53	28.4	3.35
2.07	25.3	3.23
2.98	25.1	3.22
4.08	25.6	3.24
5.12	26.7	3.28
6.23	16.6	2.81
7.90	17.3	2.85
22.4	1.19	0.171

 

Hydrolysis Results for the Test Item at pH 9 and 30°C

Hydrolysis Time [h]	Concentration [mg/L]	Ln Concentration
0.00	30.6	3.42
0.517	34.2	3.53
1.03	34.1	3.53
1.53	27.1	3.30
2.07	29.5	3.39
2.98	37.4	3.62
4.08	19.0	2.95
5.12	22.3	3.11
6.23	15.8	2.76
7.90	5.03	1.61
22.4	0.0514*	2.97*

* Value below the LOQ; not taken into further accounts

 

Hydrolysis Results for the Test Item at pH 9 and 50°C

Hydrolysis Time [min]	Concentration [mg/L]	Ln Concentration
0.00	35.2	3.56
3.08	48.0	3.87
5.25	28.7	3.36
10.3	33.6	3.51
15.5	27.3	3.31
20.1	50.3	3.92
30.9	15.4	2.74
46.0	7.17	1.97
60.7	7.13	1.96
90.4	1.43	0.357
151	0.198*	1.62*

* Value below the LOQ; not taken into further accounts

Reaction Rate Constants and Half-Lives at pH 4

	pH 4	pH 4	pH 4
	10°C	20°C	30°C
Slope of regression graph	-0.0721	-0.271	-0.375
Correlation factor [r2]	0.993	0.944	0.829
Reaction rate constant kobs[1/s]	0.00120	0.00361	0.00620
Half-life T½[min]	9.61	3.20	1.86
Confidence interval of half-life T½[min]	8.17 to 11.0	2.72 to 3.73	1.23 to 2.47
Half-life T½ [h]	0.160	0.0533	0.0310
Confidence interval of half-life T½[h]	0.136 to 0.183	0.0453 to 0.0622	0.0205 to 0.0412

 

Reaction Rate Constants and Half-Lives at pH 7

	pH 7	pH 7	pH 7
	20°C	30°C	50°C
Slope of regression graph	-0.0216	-0.0458	-0.195
Correlation factor [r2]	0.998	0.996	0.993
Reaction rate constant kobs[1/s]	0.00000601	0.0000127	0.0000542
Half-life T½[h]	32.1	15.1	3.55
Confidence interval of half-life T½[h]	30.7 to 33.5	14.0 to 16.3	3.34 to 3.75
Half-life T½ [d]	1.34	0.630	0.148
Confidence interval of half-life T½[d]	1.28 to 1.40	0.585 to 0.680	0.139 to 0.156

 

Reaction Rate Constants and Half-Lives at pH 9

	pH 9	pH 9	pH 9
	20°C	30°C	50°C
Slope of regression graph	-0.148	-0.194	-0.0366
Correlation factor [r2]	0.951	0.725	0.911
Reaction rate constant kobs[1/s]	0.0000411	0.0000538	0.000610
Half-life T½[h]	4.69	3.58	0.316
Confidence interval of half-life T½[h]	3.64 to 5.73	2.25 to 5.20	0.175 to 0.433
Half-life T½ [d]	0.195	0.149	0.0132
Confidence interval of half-life T½[d]	0.152 to 0.239	0.0936 to 0.217	0.00730 to 0.0181

 

Arrhenius calculations

Results of Arrhenius Calculations

pH value	Temperature [°C]	-EA/R	ln A	EA [J*mol-1]
4	10 20 30	-7065	18.31	5.87E4
7	20 30 50	-6964	11.72	5.79E4
9	20 30 50	-8924	20.06	7.42E4

 

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis half-lives of 3.2 minutes at pH 4, 32.1 hours at pH 7 and 4.69 hours at pH 9 and 20°C were obtained for the substance using a relevant test method and in compliance with GLP. The result is considered to be reliable.

Executive summary:

Hydrolysis as a function of pH was determined according to OECD Guideline No. 111 and Council Regulation (EC) No. 440/2008, Method C.7 for the test item 3-(triethoxysilyl)propanethiol (batch number: 4263180522) from 2019-07-02 to 2019-09-07 at the test facility.

Analyses of the test item 3-(triethoxysilyl)propanethiol were performed via GC-MS/MS on a capillary analytical column using the test item as external standard. The analytical method was validated with satisfactory results with regard to linearity, accuracy, precision and specificity.

The preliminary test was conducted with a test item concentration of 40 mg/L in buffer solutions at pH 4, 7 and 9 at 50°C. For all pH-values, the definitive test was performed, as a significant reduction (> 10%) of the test item concentration was observed in the preliminary test.

The definitive test was conducted with a test item concentration of 40 mg/L in buffer solutions at pH 7 and 9 at temperatures of 20, 30 and 50 °C as well as in buffer solution at pH 4 at temperatures of 10, 20 and 30°C, respectively. Samples were taken at test start (0 h) and at 8 - 10 spaced points until test end. Pure test system (buffer solution at the respective pH-value) was analyzed at test start and test end and there was no analytical interference with the test item.

Reaction rate constants, half-lives and activation energies were calculated from the analyzed samples based on a first order reaction kinetics model and are presented below.

Reaction Rate Constants and Half-Lives at pH 4

	pH 4	pH 4	pH 4	pH 4
	10°C	20°C	30°C	25°C*
Reaction rate constant kobs[1/s]	0.00120	0.00361	0.00620	0.00457
Half-life T½[min]	9.61	3.20	1.86	2.53
Half-life T½[h]	0.160	0.0533	0.0310	0.0421
Number of data points	11	9	10	EA = 5.87 · 10^4J * mol-1
Slope of regression graph	significantly non-zero	significantly non-zero	significantly non-zero

*values calculated via Arrhenius equation

EA = activation energy

Reaction Rate Constants and Half-Lives at pH 7

	pH 7	pH 7	pH 7	pH 7
	10°C	20°C	30°C	25°C*
Reaction rate constant kobs[1/s]	0.00000601	0.0000127	0.0000542	0.00000883
Half-life T½[h]	32.1	15.1	3.55	21.8
Half-life T½[d]	1.34	0.630	0.148	0.909
Number of data points	11	11	10	EA = 5.79 · 10^4J * mol-1
Slope of regression graph	significantly non-zero	significantly non-zero	significantly non-zero

*values calculated via Arrhenius equation

EA = activation energy

Reaction Rate Constants and Half-Lives at pH 9

	pH 9	pH 9	pH 9	pH 9
	10°C	20°C	30°C	25°C*
Reaction rate constant kobs[1/s]	0.0000411	0.0000538	0.000610	0.0000513
Half-life T½[h]	4.69	3.58	0.316	3.75
Half-life T½[d]	0.195	0.149	0.0132	0.156
Number of data points	11	10	10	EA = 7.42 · 10^4J * mol-1
Slope of regression graph	significantly non-zero	significantly non-zero	significantly non-zero

*values calculated via Arrhenius equation

EA = activation energy

 

The test item showed a moderate hydrolysis rate (2.4 h ≤ t1/2 ≤ 30 d) for pH 7 at 20, 30 and 50°C and for pH 9 at 20 and 30°C; and a fast hydrolysis (t1/2 ≤ 2.4 h) for pH 4 at 10, 20 and 30°C and for pH 9 at 50°C.

From the test item structure transformation products including diethoxy-, monoethoxy- and (3‐sulfanylpropyl)silanol, plus possible condensation products, can be postulated. Correspondingly non-GLP GC-MS scans were performed to clarify whether these or related molecules are detectable, with and without derivatisation. During these analyses no significant transformation product signals could be observed, therefore no further determinations were performed

Description of key information

Hydrolysis half-lives: 0.0533 hours at pH 4, 32.1 hours at pH 7 and 4.69 hours at pH 9 and 20°C (OECD 111)

Key value for chemical safety assessment

Half-life for hydrolysis:

32.1 h

at the temperature of:

20 °C

Additional information

The hydrolysis of the submission substance has been determined in accordance with OECD 111 Test Guideline and in compliance with GLP. The measured hydrolysis half-life values are:

 

pH 4: 9.61 minutes (0.16 hours) at 10°C, 3.2 minutes (0.0533 hours) at 20°C, 1.86 minutes (0.031 h) at 50°C

pH 7: 32.1 hours (1.34 days) at 20°C, 15.1 hours (0.63 days) at 30°C, 3.55 hours (0.148 days) at 50°C

pH 9: 4.69 hours (0.195 days) at 20°C, 3.58 hours (0.149 days) at 30°C, 0.316 hours (0.0132 days) at 50°C

 

At 25°C, the hydrolysis half-lives were calculated using the Arrhenius equation as follows: 2.53 minutes (0.0421 hours) at pH 4, 21.8 hours (0.909 days) at pH 7 and 3.75 hours (0.156 days) at pH 9.

 

The results are considered to be reliable and are used for assessment purposes.

 

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 0.000533 hours (approximately 2 seconds). However, it is not appropriate or necessary to attempt to predict accurately when the half-life is less than 5-10 seconds. The half-life is therefore reported as 5 seconds as a worst case.

 

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-(triethoxysilyl)propanethiol the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 7.9 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, i.e. 0.013 hours and 7.9 hours.

 

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

 

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

 

 

Hydrolysis of the read-across substance 3-(trimethoxysilyl)propane-1-thiol (CAS 4420 -74 -0)

Data for the substance, 3-(trimethoxysilyl)propane-1-thiol (CAS 4420-74-0, EC No. 224-588-5) are read across to the submission substance [3-(triethoxysilyl)propanethiol] for the following endpoints: biodegradation in water, short-term toxicity to soil macroorganisms, toxicity to STP microorganisms, skin irritation and eye irritation. For the short-term toxicity to fish, short-term toxicity to aquatic invertebrates and toxicity to algae, the available studies for 3-(trimethoxysilyl)propane-1-thiol are used as supporting studies. The formation of the same silanol hydrolysis product by the two substances is relevant to this read-across, as discussed in the appropriate sections of each endpoint.

 

For 3-(trimethoxysilyl)propane-1-thiol, hydrolysis half-lives at 20-25°C of 0.2 h at pH 4, 2.6 h at pH 7 and 0.1 h at pH 9 were determined using validated QSAR estimation methods.

 

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 0.002 h (approximately 7 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 hour. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), the half-life is approximately 5 seconds.

 

The hydrolysis products are 3-(trihydroxysilyl)propanethiol (1 mole) and methanol (3 moles).