Reaction mass of bisisopropyl peroxydicarbonate and bis-sec-butyl peroxydicarbonate and isopropyl-secbutylperoxydicarbonate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study could not be performed under GLP because NMR analyses are not available under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

no thymol was used. Only one single temperature was tested in Tier 2.

Principles of method if other than guideline:

The hydrolysis study was carried out according to OECD guideline 111, Tier 2 and 3 (OECD, 2004). It was not necessary to perform Tier 1 as the sponsor indicated the test substances to be hydrolytically unstable at all pH buffers.
Sterilization of the buffer solutions was performed by autoclaving at 121°C for 20 minutes. Sterilization of glassware was performed by heating at 180°C for at least 30 minutes.

GLP compliance:

no

Specific details on test material used for the study:

EC name: Reaction mass of bisisopropyl peroxydicarbonate and bis-sec-butyl
peroxydicarbonate and isopropyl-secbutylperoxydicarbonate
Synonym name: Mixture of peroxydicarbonates
CAS: Not applicable (multi constituent)
Batch no. 16041B0206
Water solubility: 72 tot 706 mg/L (Epi Suite 4.1)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

LC-MS/MS:
Samples of the buffer solutions were analyzed directly after sampling, using the analytical method described above. Note, adding 50% methanol (v/v) to the sample helps to increasing the stability of the sample. However be aware adding methanol only slows down the rate of hydrolysis, it doesn’t completely stop it.

NMR:
NMR – solvent extract
The samples were extracted with 2 mL deuterated chloroform for 30 minutes at room temperature. The chloroform layer was isolated and measured with 1H-NMR in a 5 mm tube.

Buffer samples
Approximately 900 μL of the water layer was diluted with 100 μL of D2O with maleic acid as internal standard to determine the water soluble hydrolysis products.
Extractions
A parallel sample was extracted with 2 mL deuterated chloroform for 30 minutes at room temperature.
The chloroform layer was isolated and measured with 1H-NMR in a 5 mm tube.

Buffers:

Buffer solutions of the pH values 7 and 9 were prepared according to the buffer systems of CLARK and LUBS and buffer solution pH 4 according KOLTHOFF and VLEESCHOUWER

Details on test conditions:

Hydrolysis of unstable substances (Tier 2):
Sterilized test buffer solutions of pH 4, 7 and 9 were prepared in glass bottles according to the description in Annex 3 of OECD 111 (OECD, 2004) and purged with nitrogen for at least 5 minutes. A stock solution of the test substance was prepared in acetonitrile. This stock solution was spiked to 100 mL volumetric flasks and filled up with the appropriate pH buffer, resulting in an initial concentration of 50 mg/L test substance. Subsequently about 10 mL of the spiked buffer solution was transferred to multiple sterile glass test vials. The vials were closed tightly and placed in a thermostatically controlled water bath in the dark at a temperature of 12 ± 0.5°C. At the moment the test vials were placed in the water bath, the first sample was taken and analyzed using the analytical method described in Annex 2.
Subsequent samples were taken on different time intervals and analyzed to determine the percentage of hydrolysis. Samples were analyzed directly after sampling in order to prevent further hydrolysis. Each buffer solution was spiked and analyzed in duplicate.
To check the pH of the buffer solutions at the test temperature, a separate glass bottle for each pH value was filled with buffer solution, without test substance, and placed in the thermostatically controlled water bath (at the test temperature). After equilibration with the temperature of the water bath, the pH of this bottle was checked.

Identification of hydrolysis products (Tier 3):
The sterilized buffer solution pH 7 was transferred to a volumetric flak and purged with nitrogen for at least 5 minutes.
A stock solution of the test substance was prepared in dichloromethane and spiked to the buffer solution. The buffer was spiked in a 100 mL volumetric flask at a concentration of approximately 50 mg/L test substance, not exceeding 1 % (v/v) of solvent. Subsequently 10 mL of the spiked buffer was transferred to multiple sterile glass test vials. The vials were closed tightly and placed in a thermostatically controlled water bath in the dark at a temperature of 12 ± 0.5°C. At the moment the test vials were placed in the water bath, the first sample was taken and analyzed using the NMR technique, described in Annex 2. Subsequent samples were taken on different time intervals and analyzed to determine which hydrolysis products were formed. Samples were analyzed directly after sampling in order to prevent further hydrolysis and/or thermal decomposition.

Duration:

48 h

pH:

4

Temp.:

12 °C

Initial conc. measured:

50 mg/L

Remarks:

test material (multi constituent)

Duration:

24 h

pH:

7

Temp.:

12 °C

Initial conc. measured:

50 mg/L

Remarks:

test material (multi constituent)

Duration:

4 h

pH:

9

Temp.:

12 °C

Initial conc. measured:

50 mg/L

Remarks:

test material (multi constituent)

Number of replicates:

2 replicates per sample time.

Positive controls:

yes

Negative controls:

yes

Statistical methods:

standard calculations as given in the OECD 111 guideline.

Transformation products:

yes

No.:

#1

No.:

#2

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

see figure for route of hydrolysis.

pH:

4

Temp.:

12 °C

Hydrolysis rate constant:

0.077 h-1

DT50:

9 h

Type:

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

Remarks on result:

other: component: IPP

pH:

4

Temp.:

12 °C

Hydrolysis rate constant:

0.062 h-1

DT50:

11 h

Type:

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

Remarks on result:

other: component: ADC

pH:

4

Temp.:

12 °C

Hydrolysis rate constant:

0.05 h-1

DT50:

14 h

Type:

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

Remarks on result:

other: component: SBP

pH:

7

Temp.:

12 °C

Hydrolysis rate constant:

0.096 h-1

DT50:

7 h

Type:

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

Remarks on result:

other: component: IPP

pH:

7

Temp.:

12 °C

Hydrolysis rate constant:

0.085 h-1

DT50:

8 h

Type:

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

Remarks on result:

other: component: ADC

pH:

7

Temp.:

12 °C

Hydrolysis rate constant:

0.067 h-1

DT50:

10 h

Type:

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

Remarks on result:

other: component: SBP

pH:

9

Temp.:

12 °C

Hydrolysis rate constant:

0.895 h-1

DT50:

0.8 h

Type:

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

Remarks on result:

other: component: IPP

pH:

9

Temp.:

12 °C

Hydrolysis rate constant:

0.687 h-1

DT50:

1 h

Type:

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

Remarks on result:

other: component: ADC

pH:

9

Temp.:

12 °C

Hydrolysis rate constant:

0.521 h-1

DT50:

1.3 h

Type:

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

Remarks on result:

other: component: SBP

Details on results:

Hydrolysis of unstable substances (Tier 2):
The hydrolysis test was performed for each pH value (4, 7 and 9) in duplicate at a temperature of 12 °C in the dark. The rate of hydrolysis increased for all components with increasing pH values. Calculations of the hydrolysis rate ware done on the decreasing concentration of the test substance, i.e. hydrolyzing into the intermediate products isopropyl hydrogen carbonate and sec-butyl hydrogen carbonate. The rate of hydrolysis from the intermediate products into the final hydrolysis products isopropanol and secbutanol could not be determined.

Identification of hydrolysis products (Tier 3):
The test substance and potential hydrolysis products could be analyzed/detected by NMR. In addition to analyzing the water phase an extraction was done to determine if there were any substances/products formed which adsorb easily at the tested concentration.
There were no additional substances present in the chloroform extracts, or quantitative differences of the hydrolysis products present in either phase.
In Figure 1, the expected hydrolysis route of ADC (one of the components of the test material) is depicted. In theory there were two possible hydrolysis routes, the one depicted below and one with different intermediate products, i.e. di-sec-butyl carbonate and sec-butyl isopropyl carbonate. However this route could be excluded by analyzing the reference substance, di-sec-butyl carbonate.
Isopropanol and sec-butanol were confirmed by analyzing reference substances.
From the NMR analyses it is concluded that the hydrolysis route of ADC is as depicted in Figure 1.
Component IPP will hydrolyze only via the route of isopropyl hydrogen carbonate as intermediate into isopropanol as final hydrolysis product. Component SBP will hydrolysis only via the route of sec-butyl hydrogen carbonate as intermediate into sec-butanol as final hydrolysis product.

NMR results:
after 3 days isopropanol and sec-butanol are present. Besides these hydrolysis products, two other substances are present. The concentration of these two substances decreases over time, as can be seen at the spectrum at day 11. These intermediate products hydrolyze further to isopropanol and sec-butanol. The intermediate products were identified with NMR as isopropyl hydrogen carbonate and sec-butyl hydrogen carbonate.

Validity criteria fulfilled:

yes

Conclusions:

The test substance is hydrolytically instable, ultimately isopropanol and sec-butanol are formed.

Executive summary:

The purpose of this study was to determine the hydrolysis rate and products of the test substance at different pH values, according to Tier 2 and 3 of OECD Guideline No. 111, at a single environmental relevant temperature.

An overview of the calculated half-lives of the test substance at the different pH values and 12 °C

are displayed in the table below.

pH	Component	t½ (h)
4	IPP	9
	ADC	11
	SBP	14
7	IPP	7
	ADC	8
	SBP	10
9	IPP	0.8
	ADC	1.0
	SBP	1.3

Description of key information

An OECD 111 (tier 2 and 3) were performed. Due to NMR analyses not being available under GLP, this study was not performed under GLP.

The test substance is hydrolytically instable and ultimately isopropanol and sec-butanol are formed as hydrolysis products.

	Component	t½ (h)
4	IPP	9
	ADC	11
	SBP	14
7	IPP	7
	ADC	8
	SBP	10
9	IPP	0.8
	ADC	1.0
	SBP	1.3

Key value for chemical safety assessment

Half-life for hydrolysis:

10 h

at the temperature of:

12 °C