1-Butanone, 2-(dimethylamino)-2-[(4-methylphenyl)methyl]-1-[4-(4-morpholinyl)phenyl]-

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

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:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

After incubation, 20 μL aliquots of the test solutions at each pH value (4, 7 and 9) were analyzed without dilution by measuring the UV/VIS signal of the test substance after HPLC separation of the injected sample solution.

Buffers:

Buffer pH 4, biphthalate (Baker, Art. n. 5657)
Buffer pH 7, phosphate (Baker, Art. no. 5656)
Buffer pH 9, borate/potassium chloride/NaOH (Baker, Art. no. 7145)

The buffer solutions were sterilized for 25 minutes in an autoclave prior to first use. Nitrogen was passed through the buffer solutions for 5 minutes except when freshly sterilized.

Details on test conditions:

EQUIPMENT:
- Glassware: all glassware, which must be inert in the pH range applied, was rinsed with sterile buffer. The hydrolysis was carried out in flasks, which were stoppered or sealed with an inert material (e.g. PTFE)
- Water bath: themostatically controlled water bath (Haake SWB 25)

STUDY DESIGN:
- Method:
The test item was dissolved in the buffer solutions and incubated at a specified temperature with the water bath kept constant at +/- 0.1°C. The concentration of the test item was determined as a function of time at each pH.
- Performance of the test:
A preliminary test was performed at 50°C +/-0.5°C at each of pH 4.0, 7.0 and 9.0.
Aliquots of each test solution were analysed in time intervals using the analytical method. Analysis was performed before incubation, after 2.4 hours and after 120 hours.
- Preparation of test solution:
pH 4, 7 and 9:
About 20 mg sample of the test substance was dissolved in 2 mL methanol. The mixture was diluted up to 100 mL with buffer solution (pH 4, 7 or 9). This mixture was ultrasonified for 5 minutes and submitted to a 0.45 μm filtration. To obtain a test solution of not more than half the water solubility, the solution was diluted 1:1 with the respective buffer. Two aliquots of this test solution of approxiamtely 50 mL each were transferred into 50 mL Erlenmeyer flasks in order to perform a duplicate test.

The test item is light sensitive therefore the equilibration of the water samples was performed in the dark. The test item handling was performed under red light.

Duration:

5 d

pH:

4

Temp.:

50

Duration:

5 d

pH:

7

Temp.:

50

Duration:

5 d

pH:

9

Temp.:

50

Number of replicates:

2 for each pH

Positive controls:

no

Negative controls:

no

Preliminary study:

The solubility of the test substance in buffer solution pH 7.0 is much lower than the solubility in buffer solution pH 4.0. In buffer solution pH 9.0, the test item is not detectable due to the low solubility.
The hydrolysis reaction after 5 days incubation is 6% for pH 4 and 8% for the pH 7.0.

Test performance:

The results of pH 4.0 and pH 7.0 showed no significant degradation of the test substance at 50 °C. The degradation of the test substance was less than 10 % after 5 days. At pH 9.0 the test substance was not detectable in any of the test solutions during the 50 °C preliminary test.
According to the EEC Directive 92/69, Section C.7, it can be concluded that the estimated half-life time of pH 4.0 and pH 7.0 is higher than one year under representative environmental conditions (25°C). At pH 9.0 no test item was detectable.
Therefore, the test subtance was considered to be hydrolytically stable at pH 4.0 and pH 7.0 and no further tests were necessary.

Transformation products:

not measured

pH:

4

Temp.:

50 °C

DT50:

> 1 yr

Type:

not specified

pH:

7

Temp.:

50 °C

DT50:

> 1 yr

Type:

not specified

Validity criteria fulfilled:

yes

Conclusions:

The test substance is considered to be hydrotically stable at pH 4 and 7 (half-life time > 1 year at 25°C). At pH 9.0 the test item was not detectable in the buffer solution at any sample time point. This indicates that the solubility of the test item in buffer solution pH 9.0 is very low. Therefore no further test was performed.

Executive summary:

In this guideline (OECD 111) study conducted to GLP standards, the test material (EC 438-340-0) was determined to be hydrolytically stable at pH 4 and 7 (half-life time > 1 year at 25°C).

Description of key information

Study conducted to recognised testing guidelines with GLP.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

50 °C

Additional information

A study on hydrolysis was conducted according to GLP and OECD 111 (RCC Ltd. 2002a). The estimated half-life time of the test substance at pH 4 and pH 7 is higher than one year under representative environmental conditions (25°C). Therefore, the test substance was considered to be hydrotically stable at pH 4 and pH 7, and no further testing was necessary.

At pH 9.0 the test substance was not detectable in any of the test solutions during the 50 °C preliminary test. This indicates that the solubility of the test subtance in buffer solution pH 9.0 is very low. Therefore no further test was performed.