[1,3-phenylenebis(1-methylethylidene)]bis[tert-butyl] peroxide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

from august 2008 to march 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 1a: GLP guideline study

Justification for type of information:

see read across rationale in Section 13.2

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2110 (Hydrolysis as a Function of pH)

Deviations:

not specified

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Triplicates dosed samples at each pH level were collected at time 0 and at one time point (pH 4, 7 and 9 sets) or three time points (ph 2.6 set) after application.

pH 4, 7 and 9: dosing were performed at time 0 after 5 days
pH 2.6: dosing were performed after 2 h, 6 h and 24h of incubation.

The pH of the samples was measured, and 5 mL of acetonitrile was added to each 10 mL of aqueous sample. Fortified samples were spiked with the test substance dose solution (Std C, 96.77 ng/mL in acetonitrile) at the dose rate of approximatively 1.0 ppb, after which acetonitrile was immediately added. the aqueous layers with added acetonitrile were transferred directly to individual amber autosampler vials and analysed for presence of the test substance by LC-MS/MS.

Buffers:

buffers solutions were prepared in volumetric glassware using distilled water and sterilized through 0.2 micron filter units prior to use.

pH4: a 0.05 M phtalate buffer was prepared by combining 2.0 mL of a 0.1 N aqueous NaOH solution and 250 mL of a 0.1 M aqueous potassium biphtalate solution and brought up to a final volume of 500 mL with distilled water.

pH7: a 0.05 M phosphate buffer was prepared by combining 148.15 mL of a 0.1 N aqueous NaOH solution and 250 mL of a 0.1 M aqueous monopotassium phosphate solution and brought up to a final volume of 500 mL with distilled water.

pH7: a 0.05 M borate buffer was prepared by combining 106.5 mL of a 0.1 N aqueous NaOH solution and 250 mL of a 0.1 M aqueous boric acid solution and brought up to a final volume of 500 mL with distilled water.

pH2.6: a 0.05 M phtalate buffer was prepared by combining 164.75 mL of a 0.1 N HCl solution and 250 mL of a 0.1 M potassium biphtalate solution and brought up to a final volume of 500 mL with distilled water.

Details on test conditions:

The hydrolysis was examined at 50 +/-1.0°C at pH 4, 7 and 9:

Each sample was spiked individually by combining 100 µL of the test substance dose solution (Std C, 96.77 ng/mL in acetonitrile) in 10 mL of the sterile buffer solution (final nominal concentration about 1 ppb). 12 samples were prepared in sterile 30 mL amber glass vials with Teflon lined screw caps. The samples were capped and protected from light. 3 dosed samples and 1 control sample for each pH were sacrificed immediately after dosing as T0.

The hydrolysis was examined at 25 +/-1.0°C at pH 2.6:

Each sample was spiked individually by combining 100 µL of the test substance dose solution (Std C, 96.77 ng/mL in acetonitrile) in 10 mL of the sterile buffer solution (final nominal concentration about 1 ppb). 18 samples were prepared in sterile 30 mL amber glass vials with Teflon lined screw caps. The samples were capped and protected from light. 3 dosed samples and 1 control sample were sacrificed immediately after dosing as T0.

Duration:

5 d

pH:

4

Duration:

5 d

pH:

7

Duration:

5 d

pH:

9

Duration:

24 h

pH:

2.6

Number of replicates:

3

Positive controls:

no

Negative controls:

no

Statistical methods:

Averages, linear regression, standard deviation, relative tandard deviation and relative error were the only statistical methods employed (Microsoft Excel)

Transformation products:

not measured

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

The low solubility of the substance in water prevent the use of larger concentration for this study. Thus, the amount of the expected breakdown product (Tert-butanol), even at 100% yield would result in amount well below the detection limits of the analytical method used.

% Recovery:

> 100

pH:

2.6

Temp.:

25 °C

Duration:

24 h

% Recovery:

64.6

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

71.4

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

77.3

pH:

9

Temp.:

50 °C

Duration:

5 d

pH:

2.6

Temp.:

25 °C

Remarks on result:

other: stable to hydrolysis

pH:

4

Temp.:

50 °C

DT50:

7.9 d

Type:

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

pH:

7

Temp.:

50 °C

DT50:

10.3 d

Type:

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

pH:

9

Temp.:

50 °C

DT50:

13.4 d

Type:

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

pH:

4

Temp.:

25 °C

DT50:

56.4 d

Type:

other: extrapolated using the Arrhenius equation

pH:

7

Temp.:

25 °C

DT50:

74.7 d

Type:

other: extrapolated using the Arrhenius equation

pH:

9

Temp.:

25 °C

DT50:

96.5 d

Type:

other: extrapolated using the Arrhenius equation

Linearity, Precision and Accuracy

correlation coefficient were > 0.999 or higher for the standard curve (Relative Standard Dviations less or equal to 9.2%) The average percent of theoritical concentration curve solutions ranged between 97.1 and 107.9%.

Each buffer system yielded greater than 89% recovery.

A small peak eluting in the same retention time as parent was present in all buffer and acetonitrile blank solutions: the average peak area for this peak was subtracted from sample and standard peak areas each analysis day.

Validity criteria fulfilled:

not specified

Executive summary:

The hydrolysis of [1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[1,1-dimethylethyl] peroxide was evaluated in a study performed in accordance with OECD testing guideline 111 and EPA OPPTS 835.2110 under GLP requirements.

 

The results from the hydrolysis test indicate that 64.6, 71.4 and 77.3% of the reaction were observed after 5 days at pH 4, 7 and 9 solutions respectively, at 50 °C. The test has demonstrated that the substance is hydrolytically stable at pH 2.6 after 24 hours. The degradation rates were calculated using first order kinetics as follows:

 

At 50°C:

 

pH 4 : half-life = 7.9 d

pH 7: half-life = 10.3 d

pH 9: half-life = 13.4 d

 

Extrapolated values at 25°C, using the Arrhenius equation:

 

pH 4 : half-life = 56.4 d

pH 7: half-life = 74.7 d

pH 9: half-life = 96.5 d

Description of key information

The hydrolysis of structurally analogous [1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[1,1-dimethylethyl] peroxide was evaluated in a study performed in accordance with OECD testing guideline 111 and EPA OPPTS 835.2110 under GLP requirements.

Extrapolated values at 25°C (using the Arrhenius equation):

 

pH 4 : half-life = 56.4 d

pH 7: half-life = 74.7 d

pH 9: half-life = 96.5 d

The read across and the results are confirmed by a hydrolysis comparison study performed according to OECD 111 Tier 3 with some modifications. From this study it was concluded that all three isomers of

di (tert-butylperoxyisopropyl)benzene (CAS 2212-81-9, 25155-25-3 & 2781-00-2) were hydrolytically stable at room temperature, pH 7 and 37 °C, pH 1.2..

Key value for chemical safety assessment

Half-life for hydrolysis:

74.7 d

at the temperature of:

25 °C

Additional information

The hydrolysis of structurally analogous [1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[1,1-dimethylethyl] peroxide was evaluated in a study performed in accordance with OECD testing guideline 111 and EPA OPPTS 835.2110 under GLP requirements.

 

The results from the hydrolysis test indicate that 64.6, 71.4 and 77.3% of the reaction were observed after 5 days at pH 4, 7 and 9 solutions respectively, at 50 °C. The test has demonstrated that the substance is hydrolytically stable at pH 2.6 after 24 hours. The degradation rates were calculated using first order kinetics as follows:

 

At 50°C:

 

pH 4 : half-life = 7.9 d

pH 7: half-life = 10.3 d

pH 9: half-life = 13.4 d

 

Extrapolated values at 25°C, using the Arrhenius equation:

 

pH 4 : half-life = 56.4 d

pH 7: half-life = 74.7 d

pH 9: half-life = 96.5 d

These results and the read across are confirmed by a Hydrolysis comparison study (Sikkens, et al., 2019).

The purpose of this study was to examine the similarity in hydrolytical stability and hydrolysis products between different isomers of di (tert-butylperoxyisopropyl)benzene (CAS 2212-81-9, 25155-25-3 & 2781-00-2)

, based on Tier 3 of OECD Guideline

No. 111, at pH 7 at room temperature and pH 1.2 at 37°C. Compared to the standard guideline criteria of <10% hydrolysis all 3 substances tested would be concluded hydrolytically stable. During this study physiologically relevant temperature and pH was tested together with room temperature conditions at pH 7 as a second set of conditions.

It can be concluded that all three substances behaved in a similar manner with the decrease of parent material based on the nominal start concentration being comparable. This study is considered valid as weight of evidence for similar hydrolysis/stability behavior of the tested materials.