2,3-epoxypropyl isopropyl ether

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2015-12-14 - 2016-02-16 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented GLP OECD 111 guideline study without deviations on the registered substance itself

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

Method 111 of the OECD Guidelines for Testing of Chemicals, 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:

Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Department of Health of the Government of the United Kingdom

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products:
pH4, 50°C: 5, 24, 29, 55, 74.5, 96.25 h
pH4, 40°C: 24, 48, 72, 96, 168, 192, 220 h
pH4, 30°C: 24, 48, 96, 168, 264, 360, 600 h
pH7, 50°C: 5, 24, 96.25, 101, 120, 125 h
pH7, 40°C: 24, 48, 72, 96, 168, 264, 360 h
pH7, 30°C: 28, 48, 96, 168, 264, 360, 600 h
pH9, 50°C: 5, 24, 96.25, 101, 120, 125 h
pH9, 40°C: 24, 48, 72, 96, 168, 264, 360 h
pH9, 30°C: 28, 48, 96, 168, 264, 360, 600 h
- Sampling intervals/times for pH measurements: see above
- Sample storage conditions before analysis: The sample solutions were taken from the water bath at various times and the pH of each solution recorded. The concentration of the sample solutions was determined by gas chromatography (GC).

Buffers:

- pH: 4, 7, 9
- Type and final molarity of buffer, Composition of sterile buffer:
pH4: Potassium hydrogen phthalate, 0.005 mol/l
pH7: Disodium hydrogen orthophosphate (anhydrous), 0.003 mol/l + Potassium dihydrogen orthophosphate, 0.002 mol/l + Sodium chloride, 0.002 mol/l
pH9: Disodium tetraborate, 0.001 mol/l + Sodium chloride, 0.002 mol/l

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: stoppered glass flasks
- Lighting: The solutions were shielded from light whilst maintained at the test temperature.
- Measures taken to avoid photolytic effects: The solutions were shielded from light whilst maintained at the test temperature.
- Measures to exclude oxygen: degassing with nitrogen to minimize dissolved oxygen content
- Is there any indication of the test material adsorbing to the walls of the test apparatus? none stated

TEST MEDIUM
- Preparation of test medium: Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 1.0 g/L in the three buffer solutions. The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility. The test solutions were split into individual vessels for each data point.
- Renewal of test solution: none

OTHER TEST CONDITIONS
- Adjustment of pH: no

Duration:

96.25 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

>= 1.12 - <= 1.14 other: g/l (range of duplicates)

Duration:

220 h

pH:

4

Temp.:

40 °C

Initial conc. measured:

1.02 other: g/l (both duplicates)

Duration:

600 h

pH:

4

Temp.:

30 °C

Initial conc. measured:

>= 0.984 - <= 0.997 other: g/l (range of duplicates)

Duration:

125 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

1.13 other: g/l (both duplicates)

Duration:

360 h

pH:

7

Temp.:

40 °C

Initial conc. measured:

1.01 other: g/l (both duplicates)

Duration:

600 h

pH:

7

Temp.:

30 °C

Initial conc. measured:

1.03 other: g/l (both duplicates)

Duration:

125 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

>= 0.923 - <= 0.945 other: g/l (range of duplicates)

Duration:

360 h

pH:

9

Temp.:

40 °C

Initial conc. measured:

>= 1.03 - <= 1.04 other: g/l (range of duplicates)

Duration:

600 h

pH:

9

Temp.:

30 °C

Initial conc. measured:

>= 0.978 - <= 0.981 other: g/l (range of duplicates)

Number of replicates:

duplicates

Positive controls:

no

Negative controls:

no

Preliminary study:

Results from the Preliminary Test/Tier 1 showed it was necessary to undertake further testing at pH 4, pH 7 and pH 9. See "Overall remarks, attachments".

Test performance:

See i.a. "Overall remarks, attachments".

Transformation products:

yes

No.:

#1

No.:

#1

No.:

#1

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

- Formation and decline of each transformation product during test: The chromatograms for hydrolyzed test solutions from Tier 1 and Tier 2 indicated that the degradation product eluted at approximately 4.8 minutes, since this peak increases as the test item peak decreases.
- Other: Ring-opening reactions dominate the reactivity of epoxides. The hydrolysis entails nucleophilic addition of water to the epoxide, as indicated by the mass difference between the molecular ions for the hydrolysis product and the test item (18 mass units). The hydrolysis product was therefore concluded to be 3-(1-methylethoxy)-1,2-propanediol, (CAS No. 17226-43-6).

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.002 h-1

DT50:

15.6 d

Type:

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

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

22.7 d

Type:

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

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

24.8 d

Type:

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

Details on results:

TEST CONDITIONS
- pH, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered (if yes): none stated

PATHWAYS OF HYDROLYSIS
- Description of pathwayS: It has been observed that the rate of hydrolysis is fairly constant but does increase slightly with a decrease in pH. As such, the hydrolysis was considered to be neutral and not particularly acid- or base- catalyzed. Ring-opening reactions dominate the reactivity of epoxides. The hydrolysis entails nucleophilic addition of water to the epoxide, as indicated by the mass difference between the molecular ions for the hydrolysis product and the test item (18 mass units).

Validity criteria fulfilled:

yes

Conclusions:

The study was classified as Klimisch 1, there is no reason to believe that the results are not reliable. Hence, the available data can be used to assess hydrolysis behaviour of the test item. The kinetics of the study have been determined to be consistent with that of a pseudo-first order reaction as the graphs of log10 concentration versus time are straight lines.
It has been observed that the rate of hydrolysis is fairly constant but does increase slightly with a decrease in pH. As such, the hydrolysis was considered to be neutral and not particularly acid- or base- catalyzed. With an estimated half-life of 22.7 days at pH7, the test item was considered hydrolitically unstable. As epoxides are very likely to undergo ring-opening via a nucleophilic addition of water to the epoxide, the hydrolysis product can be concluded to be 3-(1-methylethoxy)-1,2-propanediol (CAS No. 17226-43-6), which is indicated by MS spectrometry.

Executive summary:

Hydrolysis of CAS No.4016-14-2 at approx. 1 g/l was studied in the dark at 50ºC, 40°C, and 30°C in sterile aqueous buffered solutions at pH 4 (phthalate buffer), pH 7 (phosphate buffer) and pH 9 (borate buffer) for up to 600 h.  The experiment was conducted in accordance with Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004, and in compliance with GLP standards.  Samples were analysed by GC-FID. Identification of the transformation products was done by GC-MS.

 

The estimated rate constants at 25°C were

1.85x 10^-3h^-1(pH 4)

1.85x 10^-3h^-1(pH 7)

1.85x 10^-3h^-1(pH 9)

 

The estimated half-lives at 25°C were

15.6 days (pH 4)

22.7 days (pH 7)

24.8 days (pH 9)

 

The hydrolysis product was determined to be 3-(1-methylethoxy)-1,2-propanediol (CAS No. 17226-43-6).

 

This study is classified acceptable and satisfies the guideline requirement for hydrolysis study.

Description of key information

Hydrolysis: hydrolytically unstable, half-lives at 25°C are 15.6 days (pH 4), 22.7 days (pH 7), and 24.8 days (pH 9), hydrolysis product: 3-(1-methylethoxy)-1,2-propanediol (OECD 111, GLP)

Key value for chemical safety assessment

Half-life for hydrolysis:

22.7 d

at the temperature of:

25 °C

Additional information

There is one valid OECD 111 / EU method C.7 study under GLP on the hydrolysis of 2,3-epoxypropyl isopropyl ether available, assessed with Klimisch 1 and hence considered as sufficiently reliable to cover this endpoint.

It has been observed that the rate of hydrolysis is fairly constant but does increase slightly with a decrease in pH. As such, the hydrolysis was considered to be neutral and not particularly acid- or base- catalyzed. With half-lives at 25°C of 15.6 days (pH 4), 22.7 days (pH 7), and 24.8 days (pH 9), the test item was considered hydrolitically unstable. As epoxides are very likely to undergo ring-opening via a nucleophilic addition of water to the epoxide, the hydrolysis product found to be 3-(1-methylethoxy)-1,2-propanediol (CAS No. 17226-43-6)

There is no reason to believe that this result is not reliable, and consequently, there is no data gap identified. For further risk assessment, hydrolytical degradation of the substance needs to be regarded.