OO-tert-butyl O-(2-ethylhexyl) peroxycarbonate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 06/09/2011 to 13/12/2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was performed according to OECD Guideline 111 with GLP statement. This study report is composed of the preliminary test and the definitive test at pH 8. This study is considered reliable with restrictions based on results obtained at 15 °C, showing differences with a pseudo-first order behaviour.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

2012-07-18

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
None

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

No data

Buffers:

For pH 4, 7 and 9 of preliminary test, see "cross-reference to other study".
The definitive test was carried out at pH 8. The corresponding buffer solutions were prepared using reagent grade chemicals and ultra-pure water:
- KCl: Potassium chloride: 7.45 g (Prolabo Ref. 26764232, batch 10C310004);
- H3BO3: boric acid : 6.183 g (Sigma Ref. 33,906-7-100G, batch: 01823KE);
- NaOH 1 M: 7.94 mL (Merck Titrisol Ref. 1.09956.0001 batch: HC825834)

Estimation method (if used):

Not applicable

Details on test conditions:

PRELIMINARY TEST:
Test item was dissolved into each buffer (at pH 4, 7 and 9) at a concentration of 3 mg/L. This was obtained by adding 3.26 µL of test item into 1L of each buffer where stirring was maintained during 40 min. The solutions were then allowed to separate during 30 min. The upper parts were discarded and the solutions were transferred to 100 mL flasks. 2 replicates were prepared for each buffer. All test vessels were incubated at 50 +/- 0.5°C under stirring and kept protected from light during 5 days. The solutions were then analysed by GC.

DEFINITIVE TEST:
A stock solution at 3 mg/L of test item was prepared in pH 8 buffer (de-oxygenated by nitrogen bubbling). This concentration is close to half the solubility of the test item in water (5.39 mg/L). Temperatures used were 50, 37 and 15°C. Test vessels (100 mL) were entirely filled with test solutions. They were incubated in 3 thermostatic baths and kept protected from light during the test.

Duration:

27 h

pH:

8

Temp.:

50

Initial conc. measured:

0.88 mg/L

Duration:

73 h

pH:

8

Temp.:

37

Initial conc. measured:

0.88 mg/L

Duration:

720 h

pH:

8

Temp.:

15

Initial conc. measured:

0.88 mg/L

Number of replicates:

2

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

None

Preliminary study:

See table 1 in "Any other information on results incl. tables".
GC results showed a decrease of test item with all buffers. Hydrolysis reached 90% within 5 days with formation of 2-ethylhexanol and probably t-butanol as degradation products. GC-MS allowed only the observation of 2-ethylhexanol, quantitatively for pH 9 and at lower levels for pH 7 and 4. This result may be explained by the formation of 2-ethylhexanol derivatives that cannot be analysed in the same conditions.

Test performance:

The definitive test was performed at pH 8.

Transformation products:

yes

No.:

#1

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

Preliminary test (see "cross-reference to other study"): At pH 9, recovery was in the order of 100%, either with or without acetone added. However, in the samples at pH 4 and 7, only 10% of 2-ethylhexanol recovery was observed, even with acetone added to take possible adsorption into account.

% Recovery:

2.27

pH:

8

Temp.:

50 °C

Duration:

27 h

% Recovery:

8.52

pH:

8

Temp.:

37 °C

Duration:

73 h

% Recovery:

28.41

pH:

8

Temp.:

15 °C

Duration:

720 h

pH:

8

Temp.:

50 °C

Hydrolysis rate constant:

0.148 h-1

DT50:

4.7 h

Type:

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

pH:

8

Temp.:

37 °C

Hydrolysis rate constant:

0.036 h-1

DT50:

19.2 h

Type:

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

pH:

8

Temp.:

15 °C

Hydrolysis rate constant:

0.002 h-1

DT50:

301 h

Type:

other: At 15 °C, results show differences with a pseudo-first order behaviour. The t1/2 calculation was however used to obtain the corresponding half-life and seems to correlate well with the two points at higher temperature.

pH:

8

Temp.:

25 °C

Hydrolysis rate constant:

0.008 h-1

DT50:

83 h

Type:

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

Remarks on result:

other: extrapolated from the others (50, 37 and 15°C)

Other kinetic parameters:

None

Details on results:

For pseudo-first order behaviour, the values of hydrolysis rate constant (K.obs) can be obtained from the plots of logarithms of the concentration versus time using the expression: K.obs = - slope.
The hydrolysis rate constant derived from linear regression analysis was subsequently used to calculate the half-life for each set of test conditions, using the following equation: Half-life (t 1/2) = Ln2 / K.obs

Table 5.1.2/1: Hydrolysis of the test item at 50°C - preliminary test

Days	pH	Measured concentration (mg/L)
0	4	9.53
5		0.015
0	7	5.225
5		0.0084
0	9	1.23
5		<0.0029 (DL)

Validity criteria fulfilled:

yes

Conclusions:

The half-life of the test item at pH 8 was determined to be 83 hours at 25°C.

Executive summary:

The hydrolysis as a function of pH of the test item was assessed according to the OECD Guideline 111 with GLP statement.

A preliminary test showed that the item was unstable at pH 4, 7 and 9 at 50°C. 2 -ethylhexanol was quantitatively observed as hydrolysis product at pH 9 but only at lower levels (non-quantifiable) for pH 7 and 4. t-Butanol, the other probable degradation product was not observed. Further studies (see "cross-reference to other study") were performed at pH 7 and 9.

The objective of this study was to determine the rate of hydrolysis of the test substance at pH 8 and at different temperatures. Hydrolysis of the test item (3 mg/L solution) was conducted in order to obtain a hydrolysis rates between 20 and 70%.

At 50°C, 98% hydrolysis was observed within 27 hours. For the other temperatures, 91.4% of the test item was hydrolysed at 37°C after 73 hours and only 72% of the test item was hydrolysed at 15°C after 30 days.

At 15 °C, results show differences with a pseudo-first order behaviour. The t1/2 calculation was however used to obtain the corresponding half-life and seems to correlate well with the two points at higher temperature.

Following the half-life times calculated for the test item at pH 8 and at the 3 temperatures tested: 301 hours at 15°C, 19.2 hours at 37°C and 4.7 hours at 50°C, the value at 25°C was extrapolated from the others. The half life at pH 8 was determined to be 83 hours at 25°C.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 25/02/2009 to 04/08/2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was performed according to OECD Guideline 111 with GLP statement. This study report is composed of the preliminary test and the definitive test at pH 9. All validity criteria were fulfilled and no deviations were observed.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

2008-05-06

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
None

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

No data

Buffers:

For each buffer, solution were prepared with ultra-pure water and used as follow:
- pH4: potassium phthalate monobasic 0.1M (1000 mL) - NaOH 0.1 M (8 mL) for 2L
- pH7: potassium dihydrogen phosphate 0.1M (1000 mL) - NaOH 0.1M (592 mL) for 2L
- pH9: boric acid 0.1 M (1000 mL) - NaOH 0.1M (400 mL) for 2L

Estimation method (if used):

Not applicable

Details on test conditions:

PRELIMINARY TEST:
Test item was dissolved into each buffer (at pH 4, 7 and 9) at a concentration of 3 mg/L. This was obtained by adding 3.26 µL of test item into 1L of each buffer where stirring was maintained during 40 min. The solutions were then allowed to separate during 30 min. The upper parts were discarded and the solutions were transferred to 100 mL flasks. 2 replicates were prepared for each buffer. All test vessels were incubated at 50 +/- 0.5°C under stirring and kept protected from light during 5 days. The solutions were then analysed by GC.

DEFINITIVE TEST:
A stock solution at 3 mg/L of test item was prepared in pH 9 buffer (de-oxygenated by nitrogen bubbling) using the same procedure as for the preliminary test. This concentration is slightly higher than the half-saturation of the test item in water, which is given between 2 mg/L and 4 mg/L. Temperatures used were 50, 37 and 15°C. Test vessels (30 mL) were entirely filled with test solutions and closed with butyl rubber caps. They were incubated in 3 thermostatic baths and kept protected from light during the test.

Duration:

123.5 h

pH:

9

Temp.:

15

Initial conc. measured:

2.11 mg/L

Duration:

25.5 h

pH:

9

Temp.:

37

Initial conc. measured:

0.98 mg/L

Duration:

6 h

pH:

9

Temp.:

50

Initial conc. measured:

0.58 mg/L

Number of replicates:

2

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

None

Preliminary study:

See table 1 in "Any other information on results incl. tables".
GC results showed a decrease of test item with all buffers. Hydrolysis reached 90% within 5 days with formation of 2-ethylhexanol and probably t-butanol as degradation products. GC-MS allowed only the observation of 2-ethylhexanol, quantitatively for pH 9 and at lower levels for pH 7 and 4. This result may be explained by the formation of 2-ethylhexanol derivatives that cannot be analysed in the same conditions.

Test performance:

Results of the preliminary test allow deciding to perform a definitive test at pH9 and pH7 (see "cross-reference to other study").

Transformation products:

yes

No.:

#1

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

At pH 9, recovery was in the order of 100%, either with or without acetone added. However, in the samples at pH 4 and 7, only 10% of 2-ethylhexanol recovery was observed, even with acetone added to take possible adsorption into account.

% Recovery:

6.03

pH:

9

Temp.:

50 °C

Duration:

6 h

% Recovery:

2.55

pH:

9

Temp.:

37 °C

Duration:

25.5 h

% Recovery:

27.25

pH:

9

Temp.:

15 °C

Duration:

123.5 h

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.484 h-1

DT50:

1.43 h

Type:

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

pH:

9

Temp.:

37 °C

Hydrolysis rate constant:

0.147 h-1

DT50:

4.72 h

Type:

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

pH:

9

Temp.:

15 °C

Hydrolysis rate constant:

0.01 h-1

DT50:

69.31 h

Type:

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

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.036 h-1

DT50:

19.36 h

Type:

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

Remarks on result:

other: extrapolated from the others (50, 37 and 15°C)

Other kinetic parameters:

None

Details on results:

For pseudo-first order behaviour, the values of hydrolysis rate constant (K.obs) can be obtained from the plots of logarithms of the concentration versus time using the expression: K.obs = - slope.
The hydrolysis rate constant derived from linear regression analysis was subsequently used to calculate the half-life for each set of test conditions, using the following equation: Half-life (t 1/2) = Ln2 / K.obs

Table 5.1.2/1: Hydrolysis of the test item at 50°C - preliminary test

Days	pH	Measured concentration (mg/L)
0	4	9.53
5		0.015
0	7	5.225
5		0.0084
0	9	1.23
5		<0.0029 (DL)

Validity criteria fulfilled:

yes

Conclusions:

The half-life of the test item at pH 9 was determined to be 19.36 hours at 25°C.

Executive summary:

The hydrolysis as a function of pH of the test item was assessed according to the OECD Guideline 111 with GLP statement. The objective of the study was to determine the rate of hydrolysis of the test item in different buffers and at different temperatures.

A preliminary test showed that the item was unstable at pH 4, 7 and 9 at 50°C. 2 -ethylhexanol was quantitatively observed as hydrolysis product at pH 9 but only at lower level for pH 7 and 4. t-Butanol, the other probable degradation product was not observed. A definitive test was conducted at pH 9 and 7 (see "cross-reference to other study) and at 15, 37 and 50°C. Hydrolysis of the test item (3 mg/L solution) was conducted in order to obtain a hydrolysis rates between 20 and 70%.

For the definitive test at pH 9 (first part of the study), 94% hydrolysis was observed within 6 hours at 50°C. For the other temperatures, 97% of the test item was hydrolysed at 37°C after 25 hours and 73% after 124 hours at 15°C. Following the half-life times calculated for the test item at pH 9 and at the 3 temperatures tested: 69.31 hours at 15°C, 4.72 hours at 37°C and 1.43 hours at 50°C, the value at 25°C was extrapolated from the others. The half life at pH 9 was determined to be 19.36 hours at 25°C.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 16/05/2013 to 18/06/2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was performed according to OECD Guideline 111 with GLP statement. This study report is composed of the definitive test at pH 4. The preliminary test was already reported in pH 7 and pH 9 reports. All validity criteria were fulfilled and no deviations were observed.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

2012-07-18

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
None

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Processing of samples: dilution 2 to 100 in acetonitrile and pH 4.0 medium (final composition 50/50).

Buffers:

The definitive test was carried out at pH 4. The corresponding buffer solution was prepared using reagent grade chemicals and ultra-pure water. One litre of solution was prepared with ultra-pure water and used as follow:
- C8H5KO4: Potassium phtalate monobasic for 0.1 M solution (Merck Ref: 1.04874.0250, batch: A0332774 204): 1500 mL
- NaOH 0.1M (Merck Titrisol Ref. 1.09959.0001, batch: HC36315): 12 mL

Estimation method (if used):

Not applicable

Details on test conditions:

PRELIMINARY TEST:
Premilinary test conditions were already reported in pH 7 and 9 reports (see "cross-reference to other study").

DEFINITIVE TEST:
A stock solution at 3 mg/L of test item was prepared in pH 4 buffer (de-oxygenated by nitrogen bubbling). This concentration is close to half the solubility of the test item in water. Three temperatures were used 50, 37 and 15°C. Test vessels were entirely filled with 100 mL test solutions. They were incubated in 3 thermostatic baths and kept protected from light during the test.

Duration:

768 h

pH:

4

Temp.:

15

Initial conc. measured:

1.24 mg/L

Duration:

124 h

pH:

4

Temp.:

37

Initial conc. measured:

1.24 mg/L

Duration:

25 h

pH:

4

Temp.:

50

Initial conc. measured:

1.24 mg/L

Number of replicates:

2

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

None

Preliminary study:

see "cross-reference to other study"

Test performance:

The definitive test was performed at pH 4.

Transformation products:

not measured

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

Not applicable

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

0.116 h-1

DT50:

6 h

Type:

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

pH:

4

Temp.:

37 °C

Hydrolysis rate constant:

0.054 h-1

DT50:

12.9 h

Type:

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

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.007 h-1

DT50:

98 h

Type:

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

Remarks on result:

other: calculated using Arrhenius equation: Ln(K) = f(1/T).

pH:

4

Temp.:

15 °C

Hydrolysis rate constant:

0.002 h-1

DT50:

462 h

Type:

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

Other kinetic parameters:

None

Details on results:

For pseudo-first order behaviour, the values of hydrolysis rate constant (K.obs) can be obtained from the plots of logarithms of the concentration versus time using the expression: K.obs = - slope.
The hydrolysis rate constant derived from linear regression analysis was subsequently used to calculate the half-life for each set of test conditions, using the following equation: Half-life (t 1/2) = Ln2 / K.obs

Table 5.1.2/1: Hydrolysis of the test item at pH 4 and 50°C - definitive test

Hydrolysis of the test substance at pH 4 and 50°C
Time (hours)	pH	Measured concentration (mg/L)			Measured hydrolysis
		Sample 1	Sample 2	Mean	Remaining concentration (%)	Ln Remaining	Hydrolysis (%)
0 1 3 5 23 25	3.96 4.01 4.01 4.01 4.01 4.01	1.24 1.41 0.89 0.70 0.09 0.075	1.24 1.42 0.87 0.64 0.10 0.076	1.24 1.42 0.88 0.67 0.09 0.077	100.00 114.11 70.97 54.03 7.46 6.21	4.61 4.74 4.26 3.99 2.01 1.83	0.00 -14.11 29.03 45.97 92.54 93.79

Table 5.1.2/2: Hydrolysis of the test item at pH 4 and 37°C - definitive test

Hydrolysis of the test substance at pH 4 and 37°C
Time (hours)	pH	Measured concentration (mg/L)			Measured hydrolysis
		Sample 1	Sample 2	Mean	Remaining concentration (%)	Ln Remaining	Hydrolysis (%)
0 1 3 5 23 28 124	3.96 4.04 4.04 4.04 4.04 4.04 4.04	1.24 1.53 1.23 1.08 0.39 0.32 <QL	1.24 1.59 1.29 1.14 0.48 0.30 <QL	1.24 1.56 1.26 1.11 0.44 0.31 -	100.00 125.81 101.61 89.52 35.08 25.00 -	4.61 4.83 4.62 4.49 3.56 3.22 -	0.00 -25.81 -1.61 10.48 64.92 75.00 -

Table 5.1.2/3: Hydrolysis of the test item at pH 4 and 15°C - definitive test

Hydrolysis of the test substance at pH 4 and 15°C
Time (hours)	pH	Measured concentration (mg/L)			Measured hydrolysis
		Sample 1	Sample 2	Mean	Remaining concentration (%)	Ln Remaining	Hydrolysis (%)
0 3 5 23 28 120 188 288 456 768	-	1.24 1.23 1.30 1.21 0.88 0.52 0.80 0.46 0.48 0.38	1.24 1.58 1.63 1.43 1.40 0.75 1.01 0.62 0.71 0.55	1.24 1.41 1.47 1.32 1.14 0.64 0.91 0.54 0.60 0.47	100.00 113.31 118.15 106.45 91.94 51.21 72.98 43.55 47.98 37.50	4.61 4.73 4.77 4.67 4.52 3.94 4.29 3.77 3.87 3.62	0.00 -13.31 -18.15 -6.45 8.06 48.79 27.02 56.45 52.02 62.50

Validity criteria fulfilled:

yes

Conclusions:

The half-life time for the test substance at pH 4 and 25°C was determined using Arrhenius equation to be 98 hours.

Executive summary:

This study was performed according to OECD Guideline 111 with GLP statement to determine the rate of hydrolysis of the test substance at pH 4.

In the preliminary test, the test substance was added into each buffer (pH 4, 7 and 9; de-oxygenated by bubbling nitrogen) as follow: 3.26 µL of test item were mixed with 1L of each buffer during 45 min under stirring. The solutions were then separated during 30 min. The upper parts were discarded and the solutions were transferred to 100 mL flasks. Two replicates were prepared for each buffer. All test vessels were incubated at 50 +/- 0.5 °C under stirring and kept protected from light during five days. The solutions were then analysed by Gas Chromatography.

Gas chromatography results showed a decrease of the test substance with all buffers. Hydrolysis reached 90% within 5 days with formation of 2 -ethylhexanol and probably t-butanol as degradation products. GC-MS allowed only the observation of 2 -ethylhexanol, quantitatively for pH 9 and at lower levels for pH 7 and 4. t-Butanol, the other expected degradation product was not observed.

In the definitive test, a stock solution at 3 mg/L of test substance was prepared in pH 4 buffer (de-oxygenated by nitrogen bubbling). This concentration is close to half the solubility of the test item in water. Three temperatures were used 50, 37 and 15°C. Test vessels were entirely filled with 100 mL test solutions. They were incubated in 3 thermostatic baths and kept protected from light during the test. Samples were analyzed using UPLC/MS/MS.

At 50°C, 93.7% hydrolysis was obtained within 25 hours. At 37°C, 75% of the test item was hydrolysed after 28 hours and 98.7% after 124 hours. Only 62.5% of the test item was hydrolysed after 32 days at 15°C. The results of this test indicated pseudo-first order reaction kinetics. Therefore, the half-life time at 25°C was extrapolated from the results obtained at the 3 temperatures tested.

At pH 4, the test substance is hydrolytically unstable.

The half-life time for the test substance at pH 4 and 25°C was determined using Arrhenius equation to be 98 hours.

Reference 4

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 29/09/2009 to 17/11/2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was performed according to OECD Guideline 111 with GLP statement. This study report is composed of the preliminary test and the definitive test at pH 7. All validity criteria were fulfilled and no deviations were observed.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

2009-10-19

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
None

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

No data

Buffers:

For each buffer, solution were prepared with ultra-pure water and used as follow:
- pH4: potassium phthalate monobasic 0.1M (1000 mL) - NaOH 0.1 M (8 mL) for 2L
- pH7: potassium dihydrogen phosphate 0.1M (1000 mL) - NaOH 0.1M (592 mL) for 2L
- pH9: boric acid 0.1 M (1000 mL) - NaOH 0.1M (400 mL) for 2L

Estimation method (if used):

Not applicable

Details on test conditions:

PRELIMINARY TEST:
Test item was dissolved into each buffer (at pH 4, 7 and 9) at a concentration of 3 mg/L. This was obtained by adding 3.26 µL of test item into 1L of each buffer where stirring was maintained during 40 min. The solutions were then allowed to separate during 30 min. The upper parts were discarded and the solutions were transferred to 100 mL flasks. 2 replicates were prepared for each buffer. All test vessels were incubated at 50 +/- 0.5°C under stirring and kept protected from light during 5 days. The solutions were then analysed by GC.

DEFINITIVE TEST:
A stock solution at 3 mg/L of test item was prepared in pH 7 buffer (de-oxygenated by nitrogen bubbling) using the same procedure as for the preliminary test. This concentration is slightly higher than the half-saturation of the test item in water, which is given between 2 mg/L and 4 mg/L. Temperatures used were 50, 37 and 15°C. Test vessels (30 mL) were entirely filled with test solutions and closed with butyl rubber caps. They were incubated in 3 thermostatic baths and kept protected from light during the test.

Duration:

792.5 h

pH:

7

Temp.:

15

Initial conc. measured:

1.39 mg/L

Duration:

97.5 h

pH:

7

Temp.:

37

Initial conc. measured:

2.43 mg/L

Duration:

24 h

pH:

7

Temp.:

50

Initial conc. measured:

1.26 mg/L

Number of replicates:

2

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

None

Preliminary study:

See table 1 in "Any other information on results incl. tables".
GC results showed a decrease of test item with all buffers. Hydrolysis reached 90% within 5 days with formation of 2-ethylhexanol and probably t-butanol as degradation products. GC-MS allowed only the observation of 2-ethylhexanol, quantitatively for pH 9 and at lower levels for pH 7 and 4. This result may be explained by the formation of 2-ethylhexanol derivatives that cannot be analysed in the same conditions.

Test performance:

Results of the preliminary test allow deciding to perform a definitive test at pH9 (see "cross reference to other study") and pH7.

Transformation products:

yes

No.:

#1

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

At pH 9, recovery was in the order of 100%, either with or without acetone added. However, in the samples at pH 4 and 7, only 10% of 2-ethylhexanol recovery was observed, even with acetone added to take possible adsorption into account.

% Recovery:

4.76

pH:

7

Temp.:

50 °C

Duration:

24 h

% Recovery:

10.29

pH:

7

Temp.:

37 °C

Duration:

97.5 h

% Recovery:

39.21

pH:

7

Temp.:

15 °C

Duration:

792.5 h

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.124 h-1

DT50:

5.6 h

Type:

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

pH:

7

Temp.:

37 °C

Hydrolysis rate constant:

0.028 h-1

DT50:

25 h

Type:

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

pH:

7

Temp.:

15 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

563 h

Type:

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

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.005 h-1

DT50:

131.3 h

Type:

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

Remarks on result:

other: extrapolated from the others (50, 37 and 15°C)

Other kinetic parameters:

None

Details on results:

For pseudo-first order behaviour, the values of hydrolysis rate constant (K.obs) can be obtained from the plots of logarithms of the concentration versus time using the expression: K.obs = - slope.
The hydrolysis rate constant derived from linear regression analysis was subsequently used to calculate the half-life for each set of test conditions, using the following equation: Half-life (t 1/2) = Ln2 / K.obs

Table 5.1.2/1: Hydrolysis of the test item at 50°C - preliminary test

Days	pH	Measured concentration (mg/L)
0	4	9.53
5		0.015
0	7	5.225
5		0.0084
0	9	1.23
5		<0.0029 (DL)

Validity criteria fulfilled:

yes

Conclusions:

The half-life of the test item at pH 7 was determined to be 131.3 hours at 25°C.

Executive summary:

The hydrolysis as a function of pH of the test item was assessed according to the OECD Guideline 111 with GLP statement. The objective of the study was to determine the rate of hydrolysis of the test item in different buffers and at different temperatures.

A preliminary test showed that the item was unstable at pH 4, 7 and 9 at 50°C. 2 -ethylhexanol was quantitatively observed as hydrolysis product at pH 9 but only at lower level for pH 7 and 4. t-Butanol, the other probable degradation product was not observed. A definitive test was conducted at pH 9 (see "cross-reference to other study") and 7 and at 15, 37 and 50°C. Hydrolysis of the test item (3 mg/L solution) was conducted in order to obtain a hydrolysis rates between 20 and 70%.

For the definitive test at pH 7, 95% hydrolysis was observed within 24 hours at 50°C. For the other temperature, 89.7% of the test item was hydrolysed at 37°C after 97.5 hours and 60.8% after 792.5 hours at 15°C. Following the half-life times calculated for the test item at pH 7 and at the 3 temperatures tested: 563 hours at 15°C, 25 hours at 37°C and 5.6 hours at 50°C, the value at 25°C was extrapolated from the others. The half life at pH 7 was determined to be 131.3 hours at 25°C.

Description of key information

The results of key studies performed according to OECD Guideline 111 correspond to:
- Half-life (pH 4; 25°C) = 98 hours;
- Half-life (pH 7; 25°C)= 131.3 hours;
- Half-life (pH 8; 25°C) = 83 hours;
- Half-life (pH 9; 25°C) = 19.36 hours.

Key value for chemical safety assessment

Half-life for hydrolysis:

131.3 h

at the temperature of:

25 °C

Additional information

Four valid key studies are available to assess the hydrolysis potential of the substance as a function of pH. These studies were performed according to the OECD Guideline 111 with GLP statement.

The same preliminary test was performed for the four studies. In this preliminary test, the test substance was added into each buffer (pH 4, 7 and 9; de-oxygenated by bubbling nitrogen) as follow: 3.26 µL of test item were mixed with 1L of each buffer during 45 min under stirring. The solutions were then separated during 30 min. The upper parts were discarded and the solutions were transferred to 100 mL flasks. Two replicates were prepared for each buffer. All test vessels were incubated at 50 +/- 0.5 °C under stirring and kept protected from light during five days. The solutions were then analysed by Gas Chromatography (GC). GC results showed a decrease of the test substance with all buffers. Hydrolysis reached 90% within 5 days with formation of 2-ethylhexanol and probably t-butanol as degradation products. GC-MS allowed only the observation of 2-ethylhexanol, quantitatively for pH 9 and at lower levels for pH 7 and 4. t-Butanol, the other expected degradation product was not observed.

The definitive tests were performed at pH 4, 7, 8 and 9 (corresponding to the four key studies).

For this, a stock solution at 3 mg/L of the test substance was prepared into each buffer. All test vessels were incubated at 50, 37 and 15 °C. The solutions were then analysed along with time.

At pH 4 and 50°C, 93.7% hydrolysis was obtained after 25 hours. For the other temperatures, 98.7% of the test item was hydrolysed after 124 hours at 37°C and 62.5% after 32 days at 15°C.

At pH 7 and 50°C, 95% hydrolysis was obtained after 24 hours. For the other temperatures, 89.7% of the test item was hydrolyzed after 97.5 hours at 37°C and 60.8% after 33 days at 15°C.

At pH 8 and 50°C, 98% hydrolysis was obtained after 27 hours. For the other temperatures, 91.4% of the test item was hydrolyzed after 73 hours at 37°C and 72% after 30 days at 15°C.

At pH 9 and 50°C, 94% hydrolysis was obtained after 6 hours. For the other temperature, 97% of the test item was hydrolysed after 25 hours at 37°C and 73% after 124 hours at 15°C.

The results of these studies indicated pseudo-first order reaction kinetics. Therefore, the half-life time at 25°C was extrapolated from the results obtained at the 3 temperatures tested, for each pH, using Arrhenius equation.

The half-life times for the test substance as a function of pH are presented below:

- Half-life (pH 4; 25°C) = 98 hours;

- Half-life (pH 7; 25°C)= 131.3 hours;

- Half-life (pH 8; 25°C) = 83 hours;

- Half-life (pH 9; 25°C) = 19.36 hours.