9-[2-(2-methoxyethoxy)ethoxy]-9-[3-(oxiranylmethoxy)propyl]-2,5,8,10,13,16-hexaoxa-9-silaheptadecane

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

This study was conducted between 24 June 2016 and 18 December 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC No. 440/2008 30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

13 April 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Specification of Buffer Solutions

Buffer solution(pH) Components Concentration(mol dm-3)
4 Potassium hydrogen phthalate 0.005
7 Disodium hydrogen orthophosphate (anhydrous) 0.003
Potassium dihydrogen orthophosphate 0.002
Sodium chloride 0.002
9 Disodium tetraborate 0.001
Sodium chloride 0.002
These solutions were subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen content, all solutions cooled to test temperature before preparation of test solutions.

Details on test conditions:

Performance of the Test

Preparation of the Test Solutions
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 5.0 g/L in the three buffer solutions.
The solutions were shielded from light whilst maintained at the test temperature.
Tier 2
Results from the method development showed it was necessary to undertake further testing carried out as outlined in the following table:

pH Temperature Time Period (hours)
4 10.0 ± 0.5 °C 1.02
4 20.0 ± 0.5 °C 0.68
4 30.0 ± 0.5 °C 0.42
7 10.0 ± 0.5 °C 61.0
7 20.0 ± 0.5 °C 31.1
7 30.0 ± 0.5 °C 12.2
9 10.0 ± 0.5 °C 3.22
9 20.0 ± 0.5 °C 1.61
9 30.0 ± 0.5 °C 1.10

Positive controls:

no

Negative controls:

no

Preliminary study:

Preliminary Test/Tier 1
Tier 1 testing was not carried out as fast hydrolysis (<7 hours with 50% solvent present) of the sample was seen during the development of the method. Therefore testing was carried out at Tier 2 only.

Transformation products:

not measured

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

Identification of Hydrolysis Products – Tier 3
Usually, hydrolysis products should be identified using LC-MS or GC-MS. However, this procedure implies sufficient separation of the individual components that are present in the incubated test item solution (i.e. parent compound and hydrolysis products).
The chromatography of the incubated test item solution resulted in several peaks that could not be separated sufficiently from each other. Thus, identification of the hydrolysis products was technically not feasible. The chemical structure of the hydrolysis product(s) is most probably quite similar to the one of the parent compound.
Analysis of the hydrolyzed test solutions was further hampered due to the fast hydrolysis of the test item. The test item showed an increase and then decrease of the peaks at 1.2 and 2.0 mins as the main peak at 2.4 mins decreased. This would suggest a two fold hydrolysis as the primary break down product forms a secondary breakdown product.
Analysis of the structure of the main constituent could propose that the primary break down produce would be the cleaving of the epoxide group, the weakest link of the structure and prone cleaving under harsher pH conditions.

% Recovery:

ca. 12.1

pH:

4

Temp.:

10.4 °C

Duration:

<= 1.02 h

% Recovery:

ca. 8.31

pH:

4

Temp.:

20.4 °C

Duration:

ca. 0.68 h

% Recovery:

ca. 5.72

pH:

4

Temp.:

30.2 °C

Duration:

ca. 0.42 h

% Recovery:

ca. 47.7

pH:

7

Temp.:

10.4 °C

Duration:

ca. 61 h

% Recovery:

ca. 28.4

pH:

7

Temp.:

20.4 °C

Duration:

ca. 31.3 h

% Recovery:

ca. 26.6

pH:

7

Temp.:

30.2 °C

Duration:

<= 12.24 h

% Recovery:

ca. 18.4

pH:

9

Temp.:

10.2 °C

Duration:

ca. 3.22 h

% Recovery:

ca. 14

pH:

9

Temp.:

20.4 °C

Duration:

ca. 1.61 h

% Recovery:

ca. 7.02

pH:

9

Temp.:

30.4 °C

Duration:

ca. 1.1 h

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

ca. 4.9 h-1

DT50:

ca. 0.142 h

Type:

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

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

ca. 0.058 h-1

DT50:

ca. 12 h

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

ca. 1.8 h-1

DT50:

ca. 0.385 h

Type:

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

Details on results:

Validation
The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 500 to 7500 mg/L, with standards prepared in acetonitrile. The results were satisfactory with correlation coefficients (r) of ≥ 0.9998 being obtained.

Discussion
During method development and validation the test item was observed to hydrolyze quickly and could be analyzed directly in the buffer solutions without further sample treatment, the rates were calculated by plotting the logarithm of the measured peak areas rather than the concentrations of the test solutions. This is regarded as acceptable as the linearity assessment showed that the measured areas are directly proportional to the concentration of test item. In addition the repeatability assessment showed there was negligible error in the measured areas arising from the analytical methodology. Therefore a plot of log10 area against time has the same slope as a plot of log10 concentration, and hence gives the same calculated rate constant.
The incubation device used during the testing had a limited operating range (nominal 5 °C to 40 °C) and the set points were in 1 °C increments. However the actual test temperatures were recorded to a suitable accuracy with a calibrated thermocouple and thus can be used to suitably model the relationship between temperature and reaction rate.
The nominal 30 °C test at pH 4 hydrolyzed too rapidly to obtain the 6 data points within 90 to 10% hydrolysis. However as the plots of the available points for this test and the subsequent Arrhenius plots both showed good correlation this was considered not to have impacted the result.
The kinetics of the study have been determined to be consistent with that of a pseudo-first order reaction as the graphs of log10 area versus time are straight lines.
No significant peaks were observed at the approximate retention time of the test item on analysis of any matrix blank solutions.
It has been observed that the rate of hydrolysis increases with a move away from neutrality.

The estimated rate constant and half-life at 25 °C of the test item are shown in the following table:

pH	Estimated rate constant (hr-1) at 25 °C	Estimated half-life at 25 °C (hr)
4	4.90	0.142
7	0.0576	12.0
9	1.80	0.385

Validity criteria fulfilled:

yes

Conclusions:

The estimated rate constant and half-life at 25 °C of the test item are shown in the following table:

pH Estimated rate constant (hr-1) at 25 °C Estimated half-life at 25 °C (hr)
4 4.90 0.142
7 5.76 x 10-2 12.0
9 1.80 0.385

Executive summary:

The general physico-chemical properties of 9-[2-(2-METHOXYETHOXY)ETHOXY]-9-[3(OXIRANYLMETHOXY)PROPYL]-2,5,8,10,13,16-HEXAOXA-9-SILAHEPTADECANE have been determined.

Abiotic Degradation, Hydrolysis as a Function of pH.

Assessment of hydrolytic stability was carried out using a procedure designed to be compatible with Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. The results are as follows:

pH	Estimated rate constant (hr-1) at 25 °C	Estimated half-life at 25 °C (hr)
4	4.90	0.142
7	0.0576	12.0
9	1.80	0.385

Description of key information

Assessment of hydrolytic stability was carried out using a procedure designed to be compatible with Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. The results are as follows:

pH	Estimated rate constant (hr-1) at 25 °C	Estimated half-life at 25 °C (hr)
4	4.90	0.142
7	0.0576	12.0
9	1.80	0.385

Key value for chemical safety assessment

Half-life for hydrolysis:

12 h

at the temperature of:

25 °C