Ethyl 2-methyl-1,3-dioxolane-2-acetate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 April 2013 to 11 June 2013

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

SAMPLES
An aliquot (5 mL) of each sample was extracted with an aliquot (5 mL) of methyl tert-butyl ether (approximately 0.5 g of sodium chloride was added to aid the extraction process). These were shaken vigorously for 1 minute then left to separate and the top layer sampled for analysis.

SAMPLE BLANKS
An aliquot (5 mL) of the relevant buffer solution was extracted as per the samples.

Buffers:

The test system used sterile buffer solutions at pH’s 4, 7 and 9 (see Table 1). These solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.

Details on test conditions:

PREPARATION OF THE TEST SOLUTIONS
Stock solutions were prepared at a nominal concentration of 50 mg/L in the three buffer solutions. A 1% co-solvent of acetonitrile was used to aid dissolution. The stock solutions were split into individual glass vessels for each data point. These test solutions were shielded from light whilst maintained at the test temperatures.

PRELIMINARY TEST / TIER 1
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5 °C for a period of at least 120 hours.

TIER 2
Results from the Preliminary Test/Tier 1 showed it was necessary to undertake further testing at pH 4 and pH 9, with solutions being maintained at pH 4 at 60.0 ± 0.5 °C and 70.0 ± 0.5 °C and at pH 9 at 40.0 ± 0.5 °C, 50.0 ± 0.5 °C and 60.0 ± 0.5 °C.

Duration:

624 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

>= 49.2 - <= 50.1 mg/L

Duration:

312 h

pH:

4

Temp.:

60 °C

Initial conc. measured:

>= 48.3 - <= 48.8 mg/L

Duration:

144 h

pH:

4

Temp.:

70 °C

Initial conc. measured:

>= 48 - <= 48.5 mg/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

>= 49.2 - <= 49.5 mg/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

>= 49.1 - <= 49.4 mg/L

Duration:

72 h

pH:

9

Temp.:

40 °C

Initial conc. measured:

>= 46.8 - <= 47.1 mg/L

Duration:

54 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

>= 46.6 - <= 46.7 mg/L

Duration:

30 h

pH:

9

Temp.:

60 °C

Initial conc. measured:

>= 45.2 - <= 47.8 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Preliminary study:

- pH 4 at 50°C
The extent of hydrolysis after 624 hours indicated that further testing (Tier 2), conducted at 60.0 °C and 70.0 °C, was required to estimate the rate constant and half-life at 25 °C.
Slope = -7.27 x 10^-4
kobs = 1.67 x 10^-3 hour^-1
t½ = 414 hours

- pH 7 at 50°C
Approximately 10 % hydrolysis after 120 hours at 50 °C, equivalent to a half-life of greater than 1 year at 25 °C.

- pH 9 at 50°C
The extent of hydrolysis after 120 hours indicated that further testing (Tier 2), conducted at 40 °C, 50 °C and 60 °C, was required to estimate the rate constant and half-life at 25 °C.

Transformation products:

not specified

Key result

pH:

4

Temp.:

25 °C

DT50:

ca. 388 d

Type:

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

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Type:

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

Key result

pH:

9

Temp.:

25 °C

DT50:

ca. 11.4 d

Type:

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

Details on results:

TIER 2
- pH 9 at 40°C
Slope = -4.68 x 10^-3
kobs = 1.08 x 10^-2 hour^-1
t½ = 64.3 hours

- pH 9 at 50°C
Slope = -1.45 x 10^-2
kobs = 3.34 x 10^-2 hour^-1
t½ = 20.8 hours

- pH 9 at 60°C
Slope = -2.85 x 10^-2
kobs = 6.56 x 10^-2 hour^-1
t½ = 10.6 hours

pH 4 at 60°C
Slope = -2.42 x 10^-3
kobs = 5.58 x 10^-3 hour^-1
t½ = 124 hours

- pH 4 at 70°C
Slope = -6.44 x 10^-3
kobs = 1.48 x 10^-2 hour^-1
t½ = 46.7 hours

Table 3: Test Parameters and Half-Lives

pH	Temperature / Time period	Half-Life (t1/2)
4	50°C / 624 hrs	414 hrs
	60°C / 312 hrs	124 hrs
	70°C / 144 hrs	46.7 hrs
7	50°C / 120 hrs	846 hrs
9	50°C / 120 hrs	23.2 hrs
	40°C / 72 hrs	64.3 hrs
	50°C / 54 hrs	20.8 hrs
	60°C / 30 hrs	10.6 hrs

Table 4: Rate Constants and Estimated Half-Lives at 25 °C

pH	Rate Constant (hr^-1)	Estimated Half-Live at 25 °C
4	7.44 x 10^-5	388 days
7	n/a	> 1 year
9	2.52 x 10^-3	11.4 days

Arrhenius plots were constructed using the results generated during the study (pH 4 and pH 9 data). From the graphs, the rate constant and half-lives at 25°C were estimated to be as follows:

388 days at pH 4

11.4 days at pH 9

Identification of Hydrolysis Products - Tier 3

Based on the chemical structure of the test material, hydrolysis was considered to have occurred at the ester functional group, the hydrolysis products being 1,3-dioxolane-2-acetic acid, 2-methyl and ethanol.

The cyclic-diether group (dioxolan) was considered to be hydrolytically stable under the conditions of the test as ethers do not readily hydrolyse.

Validity criteria fulfilled:

yes

Conclusions:

The half-lives of the test material at 25°C were estimated to be 388 days at pH 4, > 1 year at pH 7, and 11.4 days at pH 9.

Executive summary:

The hydrolytic stability of the test material was investigated as a function of pH during a study which was conducted under GLP conditions and in accordance with the standardised guidelines EU Method C.7 and OECD 111.

Under the conditions of the test the half-lives of the test material at 25°C were estimated to be 388 days at pH 4, > 1 year at pH 7, and 11.4 days at pH 9.

Description of key information

t½ = 388 days (25°C at pH 4);

t½ = > 1 year (25°C at pH 7);

t½ = 11.4 days (25°C at pH 9),

EU Method C.7, OECD 111, Fox (2013)

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

The hydrolytic stability of the test material was investigated as a function of pH during a study which was conducted under GLP conditions and in accordance with the standardised guidelines EU Method C.7 and OECD 111.

Under the conditions of the test the half-lives of the test material at 25°C were estimated to be 388 days at pH 4, > 1 year at pH 7, and 11.4 days at pH 9.

The study was assigned a reliability score of 1 in line with the criteria of Klimisch (1997).