1,3-dimethyl-3-phenylbutyl acetate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

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 (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: Preliminary test: at test start (0 h) and test end (120 h); Advanced test: at test start (0 h) and at additionally 9 spaced points (21 -22.4 h, 46.1 - 47.2 h, 70.1 - 71.3 h, 142 - 144 h, 197 - 198 h, 239 - 240h, 359 - 360 h, 503 - 504 h and 724 - 725 h)
- Sampling method: Not reported
- Sampling intervals/times for pH measurements: pH measured before start of hydrolysis.
- Sampling intervals/times for sterility check: The sterility of the test solutions checked at test end.
- Sample storage conditions before analysis: samples were analysed immediately (if possible less than 30 min until start of analyses, but at least not more than 5 % of the total hydrolysis time)

Buffers:

- pH: 4, 7 (preliminary test) and 9 (preliminary and advanced tests)
- Composition of buffer:
Buffer pH 4: 0.18 g of NaOH and 5.7555 g of mono potassium citrate dissolved in 500 mL double distilled water.
Buffer pH 7: 0.7358 g of NaOH and 4.3012 g of KH2PO4 were dissolved in 500 mL double distilled water.
Buffer pH 9: 0.426 g NaOH, 1.8638 g KCI and 1.5458 g H3BO3 were dissolved in 500 mL double distilled water.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: HPLC vials, volume 4 mL
- Sterilisation method: Filtration through 0.2 µm.
- Lighting: Opaque water baths used to avoid photolytic effects.
- Measures taken to avoid photolytic effects: Opaque water baths used.
TEST MEDIUM
- Volume used/treatment: 2 mL
- Preparation of test medium: Sterile buffer solutions were spiked to a test item concentration of 40 mg/L and filled into the test containers. After the vials were sealed they were transferred into the thermostat.
- Renewal of test solution: No
- Identity and concentration of co-solvent: Acetonitrile, < 1 % (v/v)

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

40 mg/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

40 mg/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

40 mg/L

Duration:

30 d

pH:

9

Temp.:

20 °C

Initial conc. measured:

40 mg/L

Duration:

30 d

pH:

9

Temp.:

30 °C

Initial conc. measured:

40 mg/L

Duration:

30 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

40 mg/L

Number of replicates:

Duplicate samples per pH value and sampling date, single injected.

Positive controls:

no

Negative controls:

yes

Remarks:

buffer solutions

Preliminary study:

After 120 h at 50 °C, 2.58 % of the test item degraded at pH 4, 2.88 % at pH 7 and 27.4 % at pH 9.

Transformation products:

yes

No.:

#1

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

- Formation and decline of each transformation product during test: 4-Methyl-4-phenylpentan-2-ol was identified for the test condition pH 9 at 30 and 50 °C.

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0 s-1

DT50:

13 010 h

Type:

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

Remarks on result:

other: r2: 0.207; T1/2 = 542 d; Half-life estimated

pH:

9

Temp.:

30 °C

Hydrolysis rate constant:

0 s-1

DT50:

3 167 h

Type:

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

Remarks on result:

other: r2: 0.838; T1/2 = 132 d

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0 s-1

DT50:

295 h

Type:

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

Remarks on result:

other: r2: 0.998; T 1/2 = 12.3 d

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: The temperature did not differ more than 0.5 °C of the intended temperature (except pH 9 at 30 °C for 6 h with a maximum of 30.8 °C). The pH values were in the range of ± 0.1 pH. Sterility of test solutions was confirmed.

Validity criteria fulfilled:

yes

Conclusions:

The test item showed moderate hydrolysis (t1/2 ≤ 30 d) at pH 9, 50 °C. At pH 9, 20 and 30 °C only a slow hydrolysis (t1/2 > 30 d) was observed. The test item was considered hydrolytically stable at pH 4 and 7 with a half-life of > 1 year for environmentally typical temperatures.

Executive summary:

Hydrolysis as a function of pH was determined in a study according to OECD Guideline 111 and EC Method C.7 for the test item. Analyses of the test item as well as the transformation product 4-methyl-4-phenylpentan-2-ol were performed via HPLC-DAD on a reversed phase column using the test item and 4-Methyl-4-phenylpentan-2-ol as external standards. The preliminary test was conducted with a test item concentration of 40 mg/L in buffer solutions at pH 4, 7 and 9 and 50 °C. The advanced test was conducted with a test item concentration of 40 mg/L in buffer solution of pH 9 at temperatures of 20, 30 and 50 °C. Samples were taken at test start (0 h) and at 9 spaced points until test end. Buffer solutions were analysed at test start and test end and there was no analytical interference with the test item. Reaction rate constants and half-lives were calculated from the analysed samples based on a first / pseudo first order reaction kinetic model.

At pH 4 and 7 no significant elimination was observed and therefore the test item was considered as hydrolytically stable under this condition and a half-life of > 1 year could be assumed for environmentally typical temperatures. The test item showed a moderate hydrolysis rate (t1/2 ≤ 30 d) for pH 9 at 50 °C. At pH 9 at 20 and 30 °C only a slow hydrolysis (t1/2 > 30 d) was observed and at 20 °C the half live was > 1 year indicating no significant hydrolysis of the test item. 4-methyl-4-phenylpentan-2-ol was identified as transformation product via co-chromatography and quantified for the test condition pH 9 at 30 and 50 °C.

Description of key information

The test item showed moderate hydrolysis (t1/2 ≤ 30 d) at pH 9, 50 °C. At pH 9, 20 and 30 °C only a slow hydrolysis (t1/2 > 30 d) was observed. The test item was considered hydrolytically stable at pH 4 and 7 with a half-life of > 1 year for environmentally typical temperatures.

Key value for chemical safety assessment

Half-life for hydrolysis:

542 d

at the temperature of:

20 °C

Additional information

Hydrolysis as a function of pH for the test item was determined in a study according to OECD Guideline 111 and EC Method C.7 (2015). Analyses were performed by HPLC-DAD on a reversed phase column. The preliminary test was conducted with a test item concentration of 40 mg/L in buffer solutions at pH 4, 7 and 9 and 50 °C. The advanced test was conducted with a test item concentration of 40 mg/L in buffer solution of pH 9 at temperatures of 20, 30 and 50 °C. Samples were taken at test start (0 h) and at 9 spaced points until test end. Reaction rate constants and half-lives were calculated from the analysed samples based on a first / pseudo first order reaction kinetic model.

No significant elimination was observed at pH 4 and 7 and therefore the test item was considered as hydrolytically stable under this condition and a half-life of > 1 year could be assumed for environmentally typical temperatures. The test item showed a moderate hydrolysis rate (t1/2 ≤ 30 d) for pH 9 at 50 °C. At pH 9 at 20 and 30 °C only a slow hydrolysis (t1/2 > 30 d) was observed and at 20 °C the half live was > 1 year indicating no significant hydrolysis of the test item.