tert-butyl α,α-dimethylbenzyl peroxide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 11/09/2012 to 16/11/2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was performed according to OECD Guideline 111 with GLP statement. This study is valid but some solubilization problems 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:

No data

Buffers:

For each buffer, one liter of solution was prepared with ultra-pure water and used as follow:
- pH 1.2: Chlorure de potassium 0.2M (250 mL) - HCl 1N (64.5 mL)
- pH4: potassium phthalate monobasic 0.1M (500 mL) - NaOH 1N (0.4 mL)
- pH7: potassium dihydrogen phosphate 0.1M (500 mL) - NaOH 0.1M (296 mL)
- pH9: boric acid 0.1 M (500 mL) - NaOH 0.1M (213 mL)

Estimation method (if used):

Not applicable

Details on test conditions:

PRELIMINARY TEST:
The substance was dissolved by stirring during 5 minutes into each buffer (at pH 1.2, 4, 7 and 9) at 5 mg/L as water solubility was found to be close to 10 mg/L. Approximately 200 mL of each solution were transferred to 250 mL closed Schott flasks, where headspace has been purged by nitrogen. All test vessels were incubated at 50 +/- 0.5 °C and kept protected from light during five days. The solutions were then analysed by HPLC/UV.

DEFINITIVE TEST:
In order to determine the half-lives of the test substance, a definitive test was performed at pH 1.2 and at 37. A solution at 5 mg/L was prepared by dissolving 5.36 µL of the test item in 1 liter of pH 1.2 buffer (de-oxygenated by nitrogen bubbling) under stirring during 5 minutes. Approximately 200 mL of solution were transferred to 250 mL closed Schott flasks, where headspace has been purged by nitrogen. Two replicates were prepared. Test vessels were incubated at 37°C during 48 hours, up to complete hydrolysis of the test item. The solutions were then analysed by HPLC/UV.

Duration:

48 h

pH:

1.2

Temp.:

37

Initial conc. measured:

8.35 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

yes

Statistical methods:

None

Preliminary study:

See table 5.1.2/1 in "Any other information on results incl. tables".
Analytical results showed only a strong decrease of the test substance at pH 1.2, where hydrolysis appears total within 5 days at 50 °C.
Initial concentration was supposed to be near 5 mg/L. It was noted that solubility might not be complete as preparation time was much shorter than the water solubility test under slow stir conditions. On the other hand, concentrations found after 5 days at pH 4, 7 and 9 are closer of the nominal initial concentrations.

Test performance:

Results of the preliminary test allow deciding to perform a definitive test at pH 1.2 and 37°C.

Transformation products:

yes

No.:

#1

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

Degradation products were analysed after 48h hydrolysis. If the tert-butyl part cannot be analysed by LC-MS, 2-phenyl 2-propanol corresponding to the cumyl part of the peroxide, was well identified. After 48h of hydrolysis, only trace of the initial peroxide, analysed by LC-MS, remains.

% Recovery:

< 0.04

pH:

1.2

Temp.:

37 °C

Duration:

48 h

pH:

1.2

Temp.:

37 °C

Hydrolysis rate constant:

0.103 h-1

DT50:

6.7 h

Type:

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

Remarks on result:

other: See table 5.1.2/2 in "Any other information on results incl. tables"

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

Time (days)	pH	Measured concentration (mg/L)
0	1.2	2.4
5		< DL
0	4	2.6
5		3.5
0	7	2.5
5		3.7
0	9	0.8
5		3.4

DL: Detection limit 0.041 mg/L

Table 5.1.2/2: Hydrolysis of the test item at pH 1.2 and 37°C - definitive test

Measured concentration (mg/L)
Time (hours)	0	2.5	6.5	22	23.5	27.5	48
Blank	< DL
Assay A	8.5	5.9	3.6	0.7	0.7	0.4	< DL
Assay B	8.2	6.5	4.0	0.8	0.7	0.6	< DL
Mean	8.35	6.2	3.8	0.75	0.7	0.5	< DL
Remaining concentration (%)	100	74.3	45.5	9.0	8.4	6.0	< 0.04

DL: Delection limit 0.041 mg/L; QL: Quantification limit 0.14 mg/L

Initial concentration of the test item appeared higher than expected. As for the preliminary test, this can be due to some solubilization problems. However, hydrolysis kinetics is correct (y = -0.1028 x + 4.5421, with R² = 0.9972, which y = ln of mean remaining concentration and x = time (hours)).

Validity criteria fulfilled:

yes

Conclusions:

The half-life for the test substance at pH 1.2 and 37 °C was determined to be 6.7 hours.

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 substance.

A preliminary test showed that the item was stable at pH 4, 7 and 9 at 50°C during 5 days. At pH 1.2, strong hydrolysis can be observed in the same conditions. The definitive test was conducted at pH 1.2 and at 37°C.

The half-life for the test substance at pH 1.2 and 37 °C was determined to be 6.7 hours.

Description of key information

OECD Guideline 111, GLP, key study, validity 2: Half-life (pH 1.2; 37°C) = 6.7 hours, stable at pH 4, 7 and 9 at 50°C during 5 days.

Additional information

One key study is available to assess the hydrolysis potential of the substance as a function of pH, according to the OECD Guideline 111 with GLP statement. A preliminary test showed that the item was stable at pH 4, 7 and 9 at 50°C during 5 days. At pH 1.2, strong hydrolysis can be observed in the same conditions. The definitive test was conducted at pH 1.2 and at 37°C. The half-life for the test substance at pH 1.2 and 37 °C was determined to be 6.7 hours.