tert-butyl peroxypivalate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

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)

Version / remarks:

13 April 2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Version / remarks:

31 May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

- pH: 4, 7, and 9
- Composition of buffer: Buffer solution pH = 4: 5 mL 0.2 M sodium hydroxide and 625 mL 0.2 M potassium hydrogen phthalate were diluted to 2500 mL with ultra-pure water. Buffer solution pH = 7: 369.5 mL 0.2 M sodium hydroxide and 625 mL 0.2 M potassium dihydrogen phosphate were diluted to 2500 mL with ultra-pure water. Buffer solution pH = 9: 267.5 mL 0.2 M sodium hydroxide and 625 mL 0.2 M boric acid and potassium chloride were diluted to 2500 mL with ultra-pure water.

Details on test conditions:

TEST SYSTEM AND CONDITIONS:
The hydrolysis was examined at three different pH values (pH = 4, 7 and 9) in the dark.
Temperature: 50 °C +/-0.5 °C, 37 °C +/- 0.5 °C and 15 °C +/- 0.5 °C.
Light and oxygen: The hydrolysis reaction was carried out using a dark thermostat to avoid photolytic effects. Nitrogen was bubbled into the water before the preparation of the solutions in order to exclude oxygen. All glassware, water and buffer solution were sterilised.
The sterile buffer solutions were prepared using reagent grade chemicals and sterile ultra-pure water.
The pH of each buffer solution was checked with a calibrated pH meter.
The samples were analysed directly after preparation.
Sterility confirmation tests were performed at each pH level at the end of the hydrolysis experiments.

Sample preparation for identification of transformation products (tier 3 study):
The test item was dissolved in different aqueous buffer solutions (pH = 4, 7, 9). The samples were stored at 50 °C for 4 hours. Before and after the storage period the samples were measured by the previously validated reverse phase HPLC method using UV detection.

Duration:

408 h

pH:

4

Temp.:

15 °C

Initial conc. measured:

93.1 other: µg/mL

Duration:

47 h

pH:

4

Temp.:

37 °C

Initial conc. measured:

93.1 other: µg/mL

Duration:

12 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

93.1 other: µg/mL

Duration:

528 h

pH:

7

Temp.:

15 °C

Initial conc. measured:

89.4 other: µg/mL

Duration:

53 h

pH:

7

Temp.:

37 °C

Initial conc. measured:

89.4 other: µg/mL

Duration:

13 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

89.4 other: µg/mL

Duration:

408 h

pH:

9

Temp.:

15 °C

Initial conc. measured:

89.6 other: µg/mL

Duration:

53 h

pH:

9

Temp.:

37 °C

Initial conc. measured:

89.6 other: µg/mL

Duration:

11 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

89.6 other: µg/mL

Number of replicates:

Five samples were analysed at the start of the study at each pH value. Two separate tubes were analysed at each analytical occasion of hydrolysis test. One sample was taken from the control vessel.

Negative controls:

yes

Remarks:

control buffer samples

Statistical methods:

The tert-butyl peroxypivalate concentrations were calculated applying the calibration equations (linear regression curves).
For the calculation of the half lives of reactions at the different pH values the ln-transformed data of tert-butyl peroxypivalate concentrations were plotted against time. Linear regression lines were fitted on the data. The rate constant and the half lives of the reactions were obtained from the slope of this linear regression lines.
Calculation of the half lives of reactions at 20 and 25 °C: Applying Arrhenius equation the rate constant and half-live at pH = 4, 7 and 9 were calculated at 20 and 25°C. The ln-transformed data of rate constants at three temperatures of the hydrolysis test were plotted against 1/T (T= t + 273.15 °C). A line was fitted on the data and the rate constants at 20 and 25 °C were calculated from the constants and slopes of linear regression lines.

Preliminary study:

In the course of the preliminary test tert-butyl peroxypivalate proved to be hydrolytically unstable at pH = 4, pH = 7 and pH = 9.

Transformation products:

yes

No.:

#1

No.:

#2

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

- Pathways for transformation (reaction equation): tert-butyl peroxypivalate + water -> tert-butyl hydroperoxide + pivalic acid

% Recovery:

59

pH:

4

Temp.:

15 °C

Duration:

408 h

% Recovery:

29

pH:

4

Temp.:

37 °C

Duration:

47 h

% Recovery:

12

pH:

4

Temp.:

50 °C

Duration:

12 h

% Recovery:

52

pH:

7

Temp.:

15 °C

Duration:

528 h

% Recovery:

26

pH:

7

Temp.:

37 °C

Duration:

53 h

% Recovery:

11

pH:

7

Temp.:

50 °C

Duration:

13 h

% Recovery:

64

pH:

9

Temp.:

15 °C

Duration:

408 h

% Recovery:

18

pH:

9

Temp.:

37 °C

Duration:

53 h

% Recovery:

13

pH:

9

Temp.:

50 °C

Duration:

11 h

pH:

4

Temp.:

15 °C

Hydrolysis rate constant:

0.001 min-1

DT50:

500 h

Type:

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

pH:

4

Temp.:

37 °C

Hydrolysis rate constant:

0.026 min-1

DT50:

26 h

Type:

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

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

0.189 min-1

DT50:

4 h

Type:

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

pH:

7

Temp.:

15 °C

Hydrolysis rate constant:

0.001 min-1

DT50:

695 h

Type:

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

pH:

7

Temp.:

37 °C

Hydrolysis rate constant:

0.026 min-1

DT50:

27 h

Type:

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

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.181 min-1

DT50:

4 h

Type:

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

pH:

9

Temp.:

15 °C

Hydrolysis rate constant:

0.001 min-1

DT50:

721 h

Type:

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

pH:

9

Temp.:

37 °C

Hydrolysis rate constant:

0.033 min-1

DT50:

21 h

Type:

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

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

0.212 min-1

DT50:

3 h

Type:

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

Other kinetic parameters:

Applying Arrhenius equation the rate constant and half-live at pH = 4, 7 and 9 were calculated at 20 and 25 °C:
- Temperature: 20 °C, pH = 4: half-live 247 hours,
- Temperature: 20 °C, pH = 7: half-live 319 hours,
- Temperature: 20 °C, pH = 9: half-live 309 hours,
- Temperature: 25 °C, pH = 4: half-live 118 hours,
- Temperature: 25 °C, pH = 7: half-live 145 hours,
- Temperature: 25 °C, pH = 9: half-live 136 hours

Details on results:

Applying Arrhenius equation the rate constant and half-live at pH = 4, 7 and 9 were calculated at 20 and 25 °C. Results of the sterility confirmation test: There were no microorganisms detected by the sterility confirmation tests.

Tier 3 results (Identification of transformation products):

On the basis of retention times in the HPLC-UV spectra the hydrolysis degradation products of tert-butyl peroxypivalate (tert-butyl hydroperoxide and pivalic acid) were identified successfully.

Validity criteria fulfilled:

yes

Conclusions:

The hydrolysis of tert-butyl peroxypivalate in different aqueous buffer solutions (pH = 4, 7 and 9) at 15, 37 and 50 °C was investigated using HPLC-UV. Measurements revealed a fast hydrolysis of tert-butyl peroxypivalate (half-live: 4 hours) at pH = 4 and 50 °C. The degradation products of the hydrolysis of tert-butyl peroxypivalate are tert-butyl hydroperoxide and pivalic acid.

Executive summary:

The hydrolysis of tert-butyl peroxypivalate and the identifiaction of the decomposition products was assessed in accordance with the OECD guideline 111 and the EU method C.7. The hydrolysis of tert-butyl peroxypivalate in different aqueous buffer solutions (pH = 4, 7 and 9) at 15, 37 and 50 °C was investigated using HPLC-UV. Measurements revealed a fast hydrolysis of TBPPI (half-live: 4 hours) at pH = 4 and 50 °C. Applying Arrhenius equation the rate constant and half-live at pH = 4, 7 and 9 were calculated at 20 and 25 °C. The half-life at pH = 4, 7 and 9 at 20 °C are 247 hours, 319 hours and 309 hours, respectively. The half-life at pH = 4, 7 and 9 at 25 °C are 118 hours, 145 hours and 136 hours, respectively. It could be shown that the hydrolysis of tert-butyl peroxypivalate was dependent from the pH and the temperature of the aqueous media. The degradation products (tert-butyl hydroperoxide and pivalic acid) were successfully identified using HPLC-UV.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2018-09-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

yes

Remarks:

please refer to principles of method

Principles of method if other than guideline:

Objective
The purpose of this study is to investigate the decomposition of Tert-butyl peroxypivalate (CAS 927-07-1) and Tertamyl peroxypivalate (CAS 29240-17-3) at conditions representing physiological conditions in the stomach (pH 1.2 at 37 °C), and at pH7 at 23 °C as a control. It is hypothesized that these structurally similar test materials degrade via a comparable route and rate to similar types of degradation products. When these are alike is considered robust evidence of similar fate and (eco) toxicological properties. The data in this study is therefore considered of value when gathering evidence to support a read-across.

Approach
Based on the adapted Tier 3 OECD Guideline No. 111 decomposition at pH 1.2 at 37 °C and at pH7 at 20 °C were studied. It was the intention to run testing in parallel under identical conditions. The decreasing concentrations of the parent test materials were monitored in time using Nuclear Magnetic Resonance (NMR), and simultaneously the increasing concentrations of the formed hydrolysis/degradation products were monitored. The SADT’s of the substances are 20 °C and 25 °C. Therefore the data is not restricted to hydrolysis only but degradation by thermal and reactive
mechanisms may occur. The intention is to monitor all degradation products from both materials regardless of the mechanism involved. Results can then be compared and conclusions drawn regarding substance behavior.

GLP compliance:

no

Remarks:

GLP-like conditions

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

5 mm NMR tubes were filled with 1 mL of each of the the prepared test solutions. The NMR tubes with buffer solutions at pH 1.2 were placed at a temperature of 37 ± 0.5 °C and the tubes with buffer solutions at pH 7 were placed at 23 ± 0.5 °C. At different time intervals the NMR tubes were analyzed to determine the percentage of parent degradation and to identify which degradation products were formed. Hence the same vials were followed during the test period and not a vial per sample point.

Buffers:

Test vessels and buffer solutions were sterilised. Test vessels were kept under dark conditions. The pH 7 solutions for both substances at room temperature (23 °C) were kept in the NMR auto sampler during testing and hence were stored under identical conditions. Temperature was not thermostatically maintained. A GC oven set at 37 °C was used for the pH 1.2 replicates for both test substances. Temperature was checked using a calibrated thermometer, pH was measured using a pH meter. The pH buffers 1.2 and 7 were made according to Clak and Lubs, described in Annex 3 of OECD 111.
Sterilized test buffer solutions of pH 1.2 and 7 were prepared in glass bottles according to the description in Annex 3 of OECD 111 (OECD, 2004). Stock solutions were also prepared as indicated in Annex 3. Both test substances were spiked at a nominal concentration of 100 mg/kg while not exceeding 1 % (w/w) of solvent.

Duration:

96 h

pH:

1.2

Temp.:

37 °C

Remarks:

CAS 927-07-1

Duration:

96 h

pH:

1.2

Temp.:

37 °C

Remarks:

CAS 29240-17-3

Duration:

216 h

pH:

7

Temp.:

23 °C

Remarks:

CAS 927-07-1

Duration:

216 h

pH:

7

Temp.:

23 °C

Remarks:

CAS 29240-17-3

Positive controls:

no

Negative controls:

no

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

No.:

#4

% Recovery:

> 76 - < 81

Remarks on result:

other: under all test conditions (pH 1.2 and 7, at 23 and 37 °C)

Key result

pH:

1.2

Temp.:

37 °C

DT50:

13.6 h

Remarks on result:

other: CAS 927-07-1

Key result

pH:

1.2

Temp.:

37 °C

DT50:

10.6 h

Remarks on result:

other: CAS 29240-17-3

Key result

pH:

7

Temp.:

23 °C

DT50:

188 h

Remarks on result:

other: CAS 927-07-1

Key result

pH:

7

Temp.:

23 °C

DT50:

88 h

Remarks on result:

other: CAS 29240-17-3

Degradation

Both materials were found to degrade under both conditions.

 

Buffer pH 1.2

The half-lives (t½) of the test substances at pH 1.2, 37 °C were calculated to be 13.6 and 10.6 hours for, Tert-butyl peroxypivalate and Tert amyl peroxypivalate respectively. Detailed results are displayed in the following tables 1 – 4 and figures attached under "background material".

Tert-amyl peroxypivalate follows a similar degradation profile as tert-butyl peroxypivalate. Both materials degrade to their corresponding alcohols, pivalic acid, and acetone at pH1.2 and 37 °C. In addition tert-amyl peroxypivalate yields not only tert-amyl alcohol as may have been expected but also tert butyl alcohol and ethanol.

 

Buffer pH 7

The half-lives (t½) of the test substances at pH 7, 20 °C were indicated to be above 188 and 88 hours for Tert-butyl peroxypivalate and Tert amyl peroxypivalate respectively. Detailed results are displayed in Tables 1 – 4 and figures attached under "background material". Tert-amyl peroxypivalate follows a similar degradation profile as tert-butyl peroxypivalate. Both materials degrade to their corresponding alcohols, acetone and isobutene at pH7 and 23 °C. For tert-butyl peroxypivalate no pivalic acid was detected. For tert-amyl peroxypivalate pivalic acid was detected.

 

Table 1 Tert-Butyl peroxypivalate concentrations in buffer pH 1.2 at 37 °C

Sample name	Time (hours)	Concentration (mg/kg)	Log Ct	Degradation (%)
1	0	69.7	1.84	0
2	2	68.2	1.83	2
3	24	31.5	1.50	55
4	48	12.6	1.10	82
5	96	0.5	-0.30	99

 

Table 2 Tert-amyl peroxypivalate concentrations in buffer pH 1.2 at 37 °C

Sample name	Time (hours)	Concentration (mg/kg)	Log Ct	Degradation (%)
1	0	59.0	1.77	0
2	2	49.5	1.69	16
3	24	12.3	1.09	79
4	48	3.4	0.53	94
5	96	0.1	-1.0	100

 

Table 3 Tert-Butyl peroxypivalate concentrations in buffer pH 7 at 23 °C

Sample name	Time (hours)	Concentration (mg/kg)	Log Ct	Degradation (%)
1	0	62.0	1.79	0
2	2	60.9	1.78	2
3	24	56.4	1.75	9
4	48	47.9	1.68	23
5	96	40.3	1.61	35
6	216	28.4	1.45	54

 

Table 4 Tert-amyl peroxypivalate concentrations in buffer pH 7 at 23 °C

Sample name	Time (hours)	Concentration (mg/kg)	Log Ct	Degradation (%)
1	0	65.0	1.81	0
2	2	63.2	1.80	3
3	24	49.0	1.69	25
4	48	41.9	1.62	36
5	96	26.2	1.42	60
6	216	11.9	1.08	82

 

 

Quality Criteria

The following quality criteria were met:

· The test temperature at 37 °C was kept constant +/- 1 °C

· The test temperature at 23 °C was room temperature and will have fluctuated slightly. Both materials were however stored under identical conditions tested in parallel.

· Extraction efficiency of analytical control standards (for identification) were determined as 90 - 108 %

· Extraction efficiency of the parent material at T=0 was at least 80 %. (Consideration should be made to the long measurement time of the NMR. In reality these concentrations were higher still)

· The detection limit of the analytical method was sufficiently sensitive for the conducted test

· A Total mass balance was achieved in all cases at >76 %

Validity criteria fulfilled:

yes

Conclusions:

The analytical method was determined capable of measuring the parent and the main degradation products of both test materials with sufficient accuracy and recovery. A mass balance of >76 % was achieved in all cases and the degradation products were conclusively identified. The test substances are believed to have the similar degradation mechanisms. Both peroxyesters hydrolyze to the corresponding alcohol and in most cases pivalic acid. Some radical decomposition
occurs leading to the formation of isobutyl radicals CO2 and Alkoxyl radicals. The formed isobutyl radicals can react with another radical to form the observed isobutene and TBA or TAA. The formed alkoxyl radicals react and via beta scission give rise to acetone and a methyl or ethyl radical. The ethyl radical can react further with O2 to form the observed ethanol. It is unclear why no methyl radicals or the products thereof (Methanol or Methane) were observed. It is also unclear why under for tertbutylperoxypivalate no pivalic acid was observed at 23 °C pH 7.However the mass balance of 76 - 81 % suggests that other products have not been missed. Under these conditions another mechanism appears to be taking place thought to be carboxy-inversion and subsequent attack by the phosphate group in the test buffer in which the pivalic acid structure is rearranged to isobutene and CO2.

Description of key information

The hydrolysis of tert-butyl peroxypivalate in different aqueous buffer solutions (pH = 4, 7 and 9) at 15, 37 and 50 °C was investigated using HPLC-UV. Measurements revealed a fast hydrolysis of  tert-butyl peroxypivalate (half-live: 4 hours) at pH = 4 and 50 °C.  The degradation products of the hydrolysis of tert-butyl peroxypivalate are tert-butyl hydroperoxide and pivalic acid.

Key value for chemical safety assessment

Half-life for hydrolysis:

145 h

at the temperature of:

25 °C

Additional information

Key study

The hydrolysis of tert-butyl peroxypivalate and the identification of the decomposition products was assessed in accordance with the OECD guideline 111 and the EU method C.7. The hydrolysis of tert-butyl peroxypivalate in different aqueous buffer solutions (pH = 4, 7 and 9) at 15, 37 and 50 °C was investigated using HPLC-UV. Measurements revealed a fast hydrolysis of TBPPI (half-live: 4 hours) at pH = 4 and 50 °C. Applying Arrhenius equation the rate constant and half-live at pH = 4, 7 and 9 were calculated at 20 and 25°C. The half-life at pH = 4, 7 and 9 at 20 °C are 247 hours, 319 hours and 309 hours, respectively. The half-life at pH = 4, 7 and 9 at 25 °C are 118 hours, 145 hours and 136 hours, respectively. It could be shown that the hydrolysis of tert-butyl peroxypivalate was dependent from the pH and the temperature of the aqueous media. The degradation products (tert-butyl hydroperoxide and pivalic acid) were successfully identified using HPLC-UV.

 

Supporting study

The analytical method was determined capable of measuring the parent and the main degradation products of both test materials with sufficient accuracy and recovery. A mass balance of >76 % was achieved in all cases and the degradation products were conclusively identified. The test substances are believed to have the similar degradation mechanisms. Both peroxyesters hydrolyze to the corresponding alcohol and in most cases pivalic acid. Some radical decomposition occurs leading to the formation of isobutyl radicals, CO2 and Alkoxyl radicals. The formed isobutyl radicals can react with another radical to form the observed isobutene and TBA or TAA. The formed alkoxyl radicals react and via beta scission give rise to acetone and a methyl or ethyl radical. The ethyl radical can react further with O₂ to form the observed ethanol. It is unclear why no methyl radicals or the products thereof (Methanol or Methane) were observed. It is also unclear why under for tertbutylperoxypivalate no pivalic acid was observed at 23 °C pH7. However, the mass balance of 76 - 81 % suggests that other products have not been missed. Under these conditions another mechanism appears to be taking place thought to be carboxy-inversion and subsequent attack by the phosphate group in the test buffer in which the pivalic acid structure is rearranged to isobutene and CO₂.