Diethyl sulphate, compound with 2-(heptadec-8-enyl)-4,5-dihydro-1H-imidazole-1-ethanol (1:1)

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-09-23 to 2021-12-29

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:

Adopted: 13 April 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- lot number of test material: 10419
- Purity: 93%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Dry and dark at ambient temperature (20 – 30 °C)
Date of Manufacture: 23/04/2021
- Expiry Date: 23/04/2023

Radiolabelling:

no

Analytical monitoring:

not specified

Details on sampling:

- Sampling intervals for the parent/transformation products:
- Sampling method:
- Sampling methods for the volatile compounds, if any:
- Sampling intervals/times for pH measurements:
- Sampling intervals/times for sterility check:
- Sample storage conditions before analysis:
- Other observation, if any (e.g.: precipitation, color change etc.):

Buffers:

- pH:
pH 4: An aliquot of 4.0 mL of 0.1 N sodium hydroxide solution and 500.0 mL of 0.1 M potassium biphthalate solution was transferred into a 1000 mL volumetric flask and the volume was made up to the mark using Milli-Q water. The pH of the resulting buffer solution was found to be 4.00.
An aliquot of 4.0 mL of 0.1 N sodium hydroxide solution and 500.0 mL of 0.1 M potassium biphthalate solution was transferred into a 1000 mL volumetric flask and the volume was made up to the mark using Milli-Q water. The pH of the resulting buffer solution was found to be 4.01.

pH 7:
An aliquot of 889.90 mL of 0.1 N sodium hydroxide solution and 1500.0 mL of 0.1 M potassium phosphate solution was diluted to 3000 mL with Milli-Q water. The pH of the resulting buffer solution was found to be 7.00.
An aliquot of 296.30 mL of 0.1 N sodium hydroxide solution and 500.0 mL of 0.1 M potassium phosphate solution was transferred into a 1000 mL volumetric flask and the volume was made up to the mark using Milli-Q water.
The pH of the resulting buffer solution was found to be 7.00.

pH 9:
An aliquot of 639.0 mL of 0.1 N sodium hydroxide solution and 1500.0 mL of 0.1 M boric acid solution was diluted to 3000 mL with Milli-Q water. The pH of the resulting buffer solution was found to be 9.01.
An aliquot of 213.0 mL of 0.1 N sodium hydroxide solution and 500.0 mL of 0.1 M boric acid solution was transferred into a 1000 mL volumetric flask and the volume was made up to the mark using Milli-Q water. The pH of the resulting buffer solution was found to be 9.01.

- Type and final molarity of buffer: 0.1 M

Details on test conditions:

TEST SYSTEM
- Sterilisation method: The glassware (before use), Milli-Q water and prepared buffer solutions were sterilized by autoclaving at 121.0 °C for about 15 minutes and filtered by passing through 0.2 μm sterilized filter and oxygen in the solutions was excluded by sonication for five minutes.

- Measures taken to avoid photolytic effects: The prepared test item solutions taken in test tubes covered with aluminium foil and kept in dark incubator in order to avoid photolytic effects

- Measures to exclude oxygen: Bubbled with nitrogen to avoid oxygen.


TEST MEDIUM
- Kind and purity of water: Milli-Q water

Number of replicates:

The test item was fortified in three different buffer solutions of pH 4, 7 and 9 at two different levels in five replicates.

Positive controls:

no

Negative controls:

no

Remarks:

blank solutions

Preliminary study:

The preliminary test results revealed that the rate of hydrolysis (percent degradation) of the test item after 5 days of incubation at 50 ± 0.5 °C was 21.67 % in pH 4 buffer, 71.06 % in pH 7 buffer and 92.82 % in pH 9 buffer, respectively. Based on the Tier 1 test results, the test item was considered as hydrolytically unstable as more than 10 % hydrolysis were obtained in pH 4, pH 7 and pH 9 buffers at 50 ± 0.5 °C after 5 days.

Transformation products:

not measured

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.01 d-1

DT50:

71.44 d

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.061 d-1

DT50:

11.38 d

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.151 d-1

DT50:

4.58 d

Details on results:

At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.2218 day-1 and 3.12 days, respectively.

Validity criteria fulfilled:

yes

Conclusions:

The results show that the hydrolytic degradation of the test item under sterile conditions strongly depends on the temperature and the pH value.
In Tier 2 test, the hydrolysis of the test item was investigated as a function of pH (4, 7 and 9) at three temperatures of 20 ± 0.5 °C, 35 ± 0.5 °C and 50 ± 0.5 °C respectively.

At pH 4, the rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.0097 day-1 and 71.44 days, respectively.
At pH 7, the rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.0609 day-1 and 11.38 days, respectively.
At pH 9, the rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.1512 day-1 and 4.58 days, respectively.
At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.2218 day-1 and 3.12 days, respectively.

Executive summary:

The hydrolysis of Diethyl sulphate, compound with 2-(heptadec-8-enyl)-4,5-dihydro-1H-imidazole-1-ethanol (1:1) as a function of pH in sterile aqueous buffer solutions of pH 4, 7 and 9 was carried out according to OECD guideline 111. The hydrolysis of the test item was analyzed by analyzing the analyte concentration at the predetermined intervals by the validated HPLC method.

At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.2218 day^-1 and 3.12 days, respectively.

 

Description of key information

In Tier 2 test, the hydrolysis of the test item was investigated as a function of pH (4, 7 and 9) at three temperatures of 20 ± 0.5 °C, 35 ± 0.5 °C and 50 ± 0.5 °C respectively.
At pH 4, the rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.0097 day-1 and 71.44 day, respectively.
At pH 7, the rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.0609 day-1 and 11.38 day, respectively.
At pH 9, the rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.1512 day-1 and 4.58 day, respectively.
At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25 ºC was calculated and found to be 0.2218 day-1 and 3.12 day, respectively.

Key value for chemical safety assessment

Half-life for hydrolysis:

3.12 d

at the temperature of:

25 °C