2-(3,5-dimethylhex-3-en-2-yloxy)-2-methylpropyl cyclopropanecarboxylate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 25 August 2008 to 27 February 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

no

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:

EPA OPPTS 835.2110 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 17 and 18 March 2008 / Date of signature: 23 June 2008

Radiolabelling:

no

Analytical monitoring:

yes

Remarks:

GC-FID and GC-MS

Buffers:

pH 4:
- Type of buffer: Sodium acetate / acetic acid buffer pH 4.00 at 20°C
- Composition of buffer: acetic acid = 0.042 mol/L; CH3COONa.3H2O = 0.007 mol/L.

pH 7:
- Type of buffer: Ready-made concentrate (Titrisol, MERCK, Darmstadt, Germany, art. No. 9887) pH 7.00 +/- 0.02 at 20°C, concentrations after dilution
- Composition of buffer: KH2PO4 = 0.026 mol/L; Na2HPO4 = 0.041 mol/L.

pH 9:
- Type of buffer: Ready-made concentrate (Titrisol, MERCK, Darmstadt, Germany, art. No. 9889) pH 9.00 +/- 0.02 at 20°C, concentrations after dilution
- Composition of buffer: H3BO3 = 0.05 mol/L; KCl = 0.05 mol/L; NaOH = 0.022 mol/L.

In order to avoid any unnecessary excess of inorganic salts that could reduce the solubility of the test substance, these buffer solutions were diluted to 10% with double distilled water before being used as test media.

Details on test conditions:

TEST SYSTEM
Hydrolysis reactions were performed in 20 mL crimp cap amber-glass vials. A constant temperature water baths is used to maintain to +/-0.1°C the bottles temperature. For temperatures close to ambiant temperature (20°C, 25°C) a cooling unit is used. Analytical equipment capable of detecting a 10% depletion of the concentration of aqueous solutions was used.

TEST CONDITIONS
- Test substance solution: The water solubility of the test substance at 20°C is 14.0 mg/L. According to the guidelines, the initial concentration to be used for the hydrolysis reaction should not exceed the half of the saturation concentration. A nominal concentration of 5.0 mg/L was used throughout the study. Therefore, a stock solution containing 5.0 g/L of test substance in acetone was prepared. By a 1:1000 dilution of this solution with buffer solution, the test concentration, 5.0 mg/L, was obtained. The amount of carrier solvent (acetone) did not exceed 0.1%, as required by the guidelines. The solutions were stirred for minimum of 16 hours at room temperature, to allow for equilibration and complete homogenisation.
- Preliminary test (Tier 1): As the test substance was expected to be hydrolytically unstable, the preliminary test at 50°C, was performed in the conditions of the main test, to say analysis were made in time intervals which provide a minimum of six spaced data points. Solutions of the test substance in the different buffer solutions were prepared as described above. For each pH, 20 crimp cap vials (20 mL) were filled with 15.0 mL of the solution, sealed with teflon coated rubber septa, and placed in the water bath at 50°C. After temperature equilibration, a first pair of vials was extracted for each pH. This is time zero of the experiment. At given times other vials were sacrificed for analysis.
- Main test (Tier 2): The main test was performed in the exact same manner as the preliminary test, with the test temperatures and sampling times adapted to the hydrolysis rates at the different pH values.
At pH 4, the preliminary test at 50°C showed a very rapid hydrolysis, so that the minimum of six spaced data points between 10% and 90% hydrolysis was not obtained. The main test was performed at 20°C, 25°C and 30°C.
At pH 7, the preliminary test at 50°C provided results that could directly be used for the main study. In addition, the main test was performed at 60°C and 70°C.
At pH 9, the preliminary test at 50°C provided results that could directly be used for the main study. In addition, the main test was performed at 40°C and 60°C.

Duration:

75 h

pH:

4

Temp.:

20 °C

Initial conc. measured:

2.477 mg/L

Remarks:

mean value of two independent measurements / Main test

Duration:

75 h

pH:

4

Temp.:

25 °C

Initial conc. measured:

2.382 mg/L

Remarks:

mean value of two independent measurements / Main test

Duration:

120 h

pH:

4

Temp.:

30 °C

Initial conc. measured:

3.404 mg/L

Remarks:

mean value of two independent measurements / Main test

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

3.693 mg/L

Remarks:

mean value of two independent measurements / Preliminary test

Duration:

144 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

5.822 mg/L

Remarks:

mean value of two independent measurements / Preliminary test

Duration:

96 h

pH:

7

Temp.:

60 °C

Initial conc. measured:

4.634 mg/L

Remarks:

mean value of two independent measurements / Main test

Duration:

96 h

pH:

7

Temp.:

70 °C

Initial conc. measured:

4.5 mg/L

Remarks:

mean value of two independent measurements / Main test

Duration:

168 h

pH:

9

Temp.:

40 °C

Initial conc. measured:

3.714 mg/L

Remarks:

mean value of two independent measurements / Main test

Duration:

144 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

5.784 mg/L

Remarks:

mean value of two independent measurements / Preliminary test

Duration:

72 h

pH:

9

Temp.:

60 °C

Initial conc. measured:

3.658 mg/L

Remarks:

mean value of two independent measurements / Main test

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Preliminary study:

See total recovery results

Transformation products:

not measured

Remarks:

Transformation products were not quantified during the study. Complimentary analytics were performed in order to identify transformation products in selected samples- see document "Proposed Pathways of Hydrolysis_nonGLP" under Attached Background Material

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

- Pathways for transformation: See document attached in "Attached background material".

% Recovery:

0.5

pH:

4

Temp.:

50 °C

Duration:

120 h

Remarks on result:

other: Preliminary test - Average concentration determined at 120 hrs = 0.017 mg/L, T0 = 3.693 mg/L

% Recovery:

2.5

pH:

4

Temp.:

30 °C

Duration:

120 h

Remarks on result:

other: Main test - Average concentration determined at 120 hrs = 0.084 mg/L, T0 = 3.404 mg/L

% Recovery:

27.2

pH:

4

Temp.:

25 °C

Duration:

75 h

Remarks on result:

other: Main test - Average concentration determined at 75 hrs = 0.648 mg/L, T0 = 2.382 mg/L

% Recovery:

47.8

pH:

4

Temp.:

20 °C

Duration:

75 h

Remarks on result:

other: Main test - Average concentration determined at 75 hrs = 1.184 mg/L, T0 = 2.477 mg/L

% Recovery:

73.5

pH:

7

Temp.:

50 °C

Duration:

144 h

Remarks on result:

other: Preliminary test - Average concentration determined at 144 hrs = 4.281 mg/L, T0 = 5.822 mg/L

% Recovery:

68.1

pH:

7

Temp.:

60 °C

Duration:

96 h

Remarks on result:

other: Main test - Average concentration determined at 96 hrs = 3.156 mg/L, T0 = 4.634 mg/L

% Recovery:

55.6

pH:

7

Temp.:

70 °C

Duration:

96 h

Remarks on result:

other: Main - Average concentration determined at 96 hrs = 2.502 mg/L, T0 = 4.500 mg/L

% Recovery:

64.9

pH:

9

Temp.:

40 °C

Duration:

168 h

Remarks on result:

other: Main test - Average concentration determined at 168 hrs = 2.410 mg/L, T0 = 3.714 mg/L

% Recovery:

39.4

pH:

9

Temp.:

50 °C

Duration:

144 h

Remarks on result:

other: Preliminary test - Average concentration determined at 144 hrs = 2.276 mg/L, T0 = 5.784 mg/L

% Recovery:

31.5

pH:

9

Temp.:

60 °C

Duration:

72 h

Remarks on result:

other: Main test - Average concentration determined at 72 hrs = 1.152 mg/L, T0 = 3.658 mg/L

Key result

pH:

4

Temp.:

25 °C

DT50:

39 h

Type:

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

Remarks on result:

other: values calculated using the Arrhenius law

Key result

pH:

7

Temp.:

25 °C

DT50:

2 572 h

Type:

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

Remarks on result:

other: values calculated using the Arrhenius law

Key result

pH:

9

Temp.:

25 °C

DT50:

1 181 h

Type:

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

Remarks on result:

other: values calculated using the Arrhenius law

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

Results with reference substance:

No reference substance is used during the performance of the test.

Table 5.1.2/1: Analytical results for the hydrolysis tests at pH 4

Test	Temperature	Measured pH	Time (hours)	Concentration test substance (mg/L)*	Av. Relative concentration (%)
Preliminary test	50°C	4.04 / 4.03           4.05 / 4.06	0 6 24 30 48 54 120	3.653 / 3.733 0.551 / 0.516 0.023 / 0.023 0.023 / 0.023 0.018 / 0.018 0.018 / 0.018 0.017 / 0.017	100.0 14.4 0.6 0.6 0.5 0.5 0.5
Main test	30°C	4.04 / 4.03             4.05 / 4.06	0 6 24 30 48 51 54 120	3.457 / 3.350 2.585 / 2.678 1.563 / 1.437 1.256 / 1.249 0.697 / 0.615 0.580 / 0.579 0.602 / 0.536 0.085 / 0.082	100.0 77.3 44.1 36.8 19.3 17.0 16.7 2.5
Main test	25°C	4.04 / 4.03               4.08 / 4.07	0 6 24 30 48 51 54 72 75	2.398 / 2.365 0.818** / 0.737** 1.517 / 1.418 1.398 / 1.430 1.026 / 0.966 0.935 / 0.889 0.884 / 0.920 0.680 / 0.677 0.658 / 0.638	100.0 - 61.6 59.4 41.8 38.3 37.9 28.5 27.2
Main test	20°C	4.04 / 4.05               4.07 / 4.07	0 6 24 30 48 51 54 72 75	2.466 / 2.488 2.092 / 2.044 1.726 / 1.702 1.778 / 1.797 1.506 / 1.462 1.313 / 1.306 1.309 / 1.241 1.209 / 1.165 1.295 / 1.073	100.0 83.5 69.2 72.2 59.9 53.2 51.5 47.9 47.8

* two independent samples at each sampling time

** sample was considered to be an outlier and are not used during further calculations

Table 5.1.2/2: Analytical results for the hydrolysis tests at pH 7

Test	Temperature	Measured pH	Time (hours)	Concentration test substance (mg/L)*	Av. Relative concentration (%)
Preliminary test	50°C	7.04 / 7.05             7.06 / 7.08	0 6 24 48 54 120 126 144	5.767 / 5.876 5.578 / 5.290 5.162 / 5.024 5.039 / 5.005 4.985 / 5.059 4.731 / 4.332 4.629 / 4.631 4.271 / 4.291	100.0 93.3 87.5 86.3 86.3 77.8 79.5 73.5
Main test	60°C	7.04 / 7.03                 7.08 / 7.05	0 16 40 48 64 68 72 88 92 96	4.944 / 4.324 3.932 / 3.856 3.703 / 3.573 3.625 / 3.539 3.757 / 3.826 3.382 / 3.326 3.465 / 3.357 3.274 / 3.239 3.192 / 3.449 3.099 / 3.213	100.0 84.0 78.5 77.7 81.8 72.4 73.6 70.3 71.7 68.1
Main test	70°C	7.03 / 7.02                 7.04 / 7.04	0 16 40 48 64 68 72 88 92 96	4.638 / 4.361 4.044 / 3.452 3.318 / 3.456 3.464 / 3.003 3.074 / 3.167 2.890 / 2.858 2.795 / 2.948 2.652 / 2.511 2.436 / 2.375 2.520 / 2.484	100.0 83.3 75.3 71.9 69.4 63.9 63.8 57.4 53.5 55.6

* two independent samples at each sampling time

Table 5.1.2/3: Analytical results for the hydrolysis tests at pH 9

Test	Temperature	Measured pH	Time (hours)	Concentration test substance (mg/L)*	Av. Relative concentration (%)
Main test	40°C	8.87 / 8.89               8.88 / 8.87	0 6 24 27 30 48 72 144 168	3.986 / 3.442 3.640 / 3.328 3.529 / 3.285 2.738 / 3.157 3.154 / 3.213 3.113 / 2.942 2.730 / 2.757 2.252 / 2.188 2.322 / 2.499	100.0 93.8 91.4 79.4 85.7 81.5 73.9 59.8 64.9
Preliminary test	50°C	8.81 / 8.82             8.79 / 8.82	0 6 24 48 54 120 126 144	5.713 / 5.856 5.370 / 5.529 4.676 / 4.533 4.284 / 4.196 4.199 / 4.103 2.661 / 2.572 2.612 / 2.553 2.235 / 2.318	100.0 94.2 79.6 73.3 71.8 45.2 44.6 39.4
Main test	60°C	8.79 / 8.81               8.81 / 8.82	0 6 24 27 30 48 51 54 72	3.917 / 3.400 3.371 / 3.046 2.665 / 2.367 2.230 / 2.284 2.178 / 2.005 1.616 / 1.616 1.660 / 1.794 1.531 / 1.273 1.189 / 1.114	100.0 87.7 68.6 51.7 57.2 44.2 47.2 38.3 31.5

* two independent samples at each sampling time

Validity criteria fulfilled:

yes

Conclusions:

The half-life time of the test substance at 25°C is 39 hours in aqueous buffer solution at pH 4.
The half-life time of the test substance at 25°C is 2572 hours in aqueous buffer solution at pH 7.
The half-life time of the test substance at 25°C is 1181 hours in aqueous buffer solution at pH 9.

Executive summary:

An abiotic degradation study (hydrolysis as a function of pH) was carried out with the test substance according to OECD Guideline 111 under GLP compliance.

Hydrolysis is one of the most common reactions controlling abiotic degradation and is therefore potentially a significant degradation pathway for substances in the environment.

Hydrolysis behaviour needs to be examined at pH values normally found in the environment (pH 4 to 9). Other potentially degrading agents (light, oxygen, microorganisms) must be excluded. In dilute solutions, the kinetics of hydrolysis is generally pseudo-first order at fixed pH and temperature. The concentration of the test substance is determined as a function of time. The logarithms of the concentrations are plotted against time and the slope of the resulting straight line (assuming first order or pseudo-first order behaviour) gives the rate constant and the half-life time.

Preliminary tests, performed at 50°C, showed that after 120 hours, more than 10% hydrolysis occurred at all three pH values of 4, 7 and 9.

Therefore, at all three pH values of 4, 7 and 9, a main test (Tier 2) was performed.

The half-life time of the test substance at 25°C is 39 hours in aqueous buffer solution at pH 4.

The half-life time of the test substance at 25°C is 2572 hours in aqueous buffer solution at pH 7.

The half-life time of the test substance at 25°C is 1181 hours in aqueous buffer solution at pH 9.

Description of key information

OECD Guideline 111, EU Method C.7, GLP, key study, validity 2:

Half life time at 25°C and pH 4 = 39 hours, equivalent to 1.6 days;

Half life time at 25°C and pH 7 = 2572 hours, equivalent to 107.2 days;

Half life time at 25°C and pH 9 = 1181 hours, equivalent to 49.2 days.

Key value for chemical safety assessment

Half-life for hydrolysis:

107.2 d

at the temperature of:

25 °C

Additional information

A key study is available, to assess the abiotic degradation of the registered substance as a function of pH in aqueous solution, according to international guidelines with GLP statement. Preliminary tests, performed at 50°C, showed that after 120 hours, more than 10% hydrolysis occurred at all three pH values of 4, 7 and 9. Therefore, at all three pH values of 4, 7 and 9, a main test (Tier 2) was performed.

The half-life time of the test substance at 25°C is 39 hours in aqueous buffer solution at pH 4.

The half-life time of the test substance at 25°C is 2572 hours in aqueous buffer solution at pH 7.

The half-life time of the test substance at 25°C is 1181 hours in aqueous buffer solution at pH 9.