(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 Jan 2020 - 19 Jun 2020

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:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Appearance/Physical state: clear, colourless, liquid
- Batch: 09892803
- Purity: 99.9% (98.8% which excludes optical isomer)
- Expiry / Retest date: 15 February 2023
- Storage conditions: room temperature, in the dark

Analytical monitoring:

yes

Details on sampling:

Duplicate sample solutions were taken initially (0 hours) from the stock solution and from the waterbath at various time points. The pH of each solution was recorded. The concentration of test item in the sample solutions was determined by high performance liquid chromatography (HPLC).

An aliquot of each sample solution was diluted by a factor of 2 using methanol (pH 4, pH 7 and pH 9 during tier 1) or acetonitrile (pH 9 during tier 2).

The standard and sample solutions were analyzed by HPLC using the following conditions:
- HPLC System: Agilent Technologies 1200, incorporating workstation and autosampler
- Detector type: variable wavelength (VW)
- Column: YMC Triart C8 (150 x 4.6 mm id)
- Column temperature: 30 °C
- Mobile phase: methanol:purified water (50:50 v/v)
- Flow-rate: 1.0 mL/min
- Injection volume: 100 µL
- VW detector wavelength: 210 nm
- Retention time: ~ 10 min

Buffers:

- pH 4: Composition of buffer: Citric acid - 30 mmol/dm; Sodium chloride - 20 mmol/dm; Sodium hydroxide - 35 mmol/dm
- pH 7: Composition of buffer: Disodium hydrogen orthophosphate (anhydrous) - 15 mmol/dm; Potassium dihydrogen orthophosphate - 10 mmol/dm; Sodium chloride - 10 mmol/dm
- pH 9: Composition of buffer: Boric acid - 25 mmol/dm; Potassium chloride - 25 mmol/dm; Sodium hydroxide - 10 mmol/dm

The buffer solutions were passed through a 0.2 µm membrane filter to sterilize and subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen.

Details on test conditions:

PREPARATION
Stock solutions of test item were prepared at a nominal concentration of 100 mg/L in the three buffer solutions; A 1% co-solvent of acetonitrile was used to aid solubility. The stock solutions were split into individual glass vessels, sealed with minimal headspace, for each data point. These sample solutions were shielded from light whilst maintained at the test temperature.

Preliminary Test/Tier 1
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5 °C for a period of 120 hours. This was extended to 336 hours for pH 7.

Tier 2
Results from the Preliminary test/Tier 1 showed it was necessary to undertake further testing at pH 4 (40 °C, 50 °C and 60 °C), pH 7 (60 °C and 70 °C) and pH 9 (30 °C, 40 °C and 50 °C) at the temperatures (± 0.5 °C) indicated. Various time points were chosen depending on the expected hydrolytic rate at that pH and temperature.

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Transformation products:

yes

No.:

#1

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

As the test item contained an ester functional group, the proposed hydrolysis products were (2-ethyl-2-methyl-1,3-dioxolan-4-yl)methanol and acrylic acid.

An example pH 4, pH 7 and pH 9 sample that had all undergone significant hydrolysis were analysed using the same analytical method but with detection by mass spectrometry (MS). In the chromatography for all three, a peak was observed that had a dominant ion with an m/z of 147 in positive mode. As the alcohol containing proposed hydrolysis product had a molecular mass of 146.2, it was considered that the ion detected by MS was the protonated form. The carboxylic acid containing proposed hydrolysis product was not observed by MS.

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

ca. 0.004 h-1

DT50:

ca. 7.04 d

Type:

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

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

ca. 0 h-1

DT50:

ca. 297 d

Type:

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

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

ca. 0.009 h-1

DT50:

ca. 3.4 d

Type:

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

Validity criteria fulfilled:

yes

Conclusions:

The estimated rate constant (hr^-1) and half-life at 25 °C of the test item are as follows:
pH 4: 4.10 x 10^-3; 169 hours/ 7.04 days
pH 7: 9.74 x 10^-5; 7120 hour/ 297 days
pH 9: 8.51 x 10^-3; 81.5 hours/ 3.40 days

Executive summary:

The hydrolysis as a function of pH of MEDOL-10 has been determined. 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 ad Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. The results are as follows:

pH	Estimated Rate Constant at 25 °C (hr^-1)	Estimated Half-Life at 25 °C
4	4.10 x 10^-3	169 hours	7.04 days
7	9.74 x 10^-5	7.12 x 10^3 hours	297 days
9	8.51 x 10^-3	81.5 hours	3.40 days

Description of key information

The estimated rate constant (hr^-1) and half-life at 25 °C of the test item are as follows:

pH 4: 4.10 x 10^-3; 169 hours/ 7.04 days

pH 7: 9.74 x 10^-5; 7120 hour/ 297 days

pH 9: 8.51 x 10^-3; 81.5 hours/ 3.40 days

Key value for chemical safety assessment

Half-life for hydrolysis:

297 d

at the temperature of:

25 °C

Additional information

A study was performed (Covance Laboratories Limited, 2020, Study PP82TC) to determine the rate of hydrolysis of MEDOL-10 as a function of pH. The procedure was designed to be compatible the EC Method C.7 and the OECD test guidelines 111, and was conducted in compliance with GLP.

The estimated rate constant (hr^-1) (pseudo-first order) at 25 °C of the test item were 4.10 x 10^-3, 9.74 x 10^-5 and 8.51 x 10^-3 at pH 4, 7 and 9, respectively.  The half-life at 25 °C of the test item at pH 4, 7 and 9 were 169 hours/ 7.04 days, 7120 hours/ 297 days and 81.5 hours/ 3.40 days, respectively. The transformation product believed to be 2-ethyl-2-methyl-1,3-dioxolan-4-yl)methanol.