4-chlorophthalic anhydride

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 June 2003 to 01 December 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorophthalic anhydride

EC Number:

204-251-9

EC Name:

4-chlorophthalic anhydride

Cas Number:

118-45-6

Molecular formula:

C8-H3-Cl-O3

IUPAC Name:

5-chloro-1,3-dihydro-2-benzofuran-1,3-dione

Details on test material:

- Storage conditions of test material: Approx. 22 °C

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

The Calibration Solutions were placed on the HPLC tray and the injection sequence was started.
The Hydrolysis Solutions were then prepared in 1.8-mL glass vials and placed on the tray. The ambient temperature was 22 °C. The time between Hydrolysis Solutions preparation and their HPLC analyses was ~ 3 h.

Buffers:

- pH 4 Buffer
An acetate buffer was prepared by dissolving 1.155 mL of glacial acetic acid in 1.000 L of deionized water solution (solution A; 0.02 M). Solution B was prepared by dissolving 1.64 g of anhydrous sodium acetate (or 2.72 g of the trihydrate) in 1.000 L of deionized water solution (0.02 M). Solution A (41.0 mL) and Solution B (9.0 mL) were mixed. The pH of this buffer was measured with a pH meter. This buffer (26.5 mL) was mixed with 100 mL of deionized water (5 mM buffer). The pH of the diluted buffer was measured but not adjusted unless outside ± 0.2 pH unit acceptance criterion.

- pH 7 Buffer
MOPS free acid (20.93 g; 0.05 M) was dissolved in 2.0 L of deionized water solution. The solution was titrated to pH 7.0 with approx. 20 mL of ~ 1.00 N aqueous NaOH. This buffer (10.0 mL) was mixed with 100 mL of deionized water (5 mM buffer). The pH of the diluted buffer was measured but not adjusted unless outside ± 0.2 pH unit acceptance criterion.

- pH 9 Buffer
Ethanolamine (1.222 g) was dissolved in approx. 900 mL of deionized water (0.02 M). The solution was titrated to pH 9.0 with ~ 32 mL of 1.0 M HCl, and made up to 1000 mL with deionized water. This buffer (26.5 mL) was mixed with 100 mL of deionized water (5 mM buffer). The pH of the diluted buffer was measured but not adjusted unless outside ± 0.2 pH unit acceptance criterion.

Details on test conditions:

When a solution of the test material in acetonitrile (CH3CN) was injected into the HPLC system, 3 peaks were observed using an aqueous mobile phase (~ 9.5 min), whereas a single peak was observed using a non-aqueous mobile phase (2.6 min). These results indicated that degradation (possibly hydrolysis) of the tests material occurred using the aqueous HPLC system.
This degradation was further investigated in an experiment where solutions of the test material in CH3CN/buffers (1/1, v/v; pH 4, 7, and 9) were prepared and immediately (within ~ 3 h) analysed using non-aqueous HPLC conditions.

CALIBRATION SOLUTIONS IN CH3CN
Solution SkCP3: Test material (11.11 mg) was dissolved in 10.00 mL of CH3CN solution in a volumetric flask (1.111 mg/mL).

BUFFER CALIBRATION SOLUTIONS IN CH3CN
Solution SkCP5: Test material (10.02 mg) was dissolved in 10.00 mL of CH3CN solution in a volumetric flask (1.002 mg/mL).
Diluted solution DSk: SkCP5 (1.780 mL) was diluted to 5.00 mL in CH3CN in a volumetric flask (357 μg/mL).

HYDROLYSIS SOLUTIONS
The Calibration Solutions were placed on the HPLC tray and the injection sequence was started.
The Hydrolysis Solutions were then prepared in 1.8-mL glass vials as below and placed on the tray. The ambient temperature was 22 °C. The time between Hydrolysis Solutions preparation and their HPLC analyses was ~ 3 h.
E4: 800 µL DSk, 800 µL of buffer pH 4, 178 µg/mL test material
E7: 800 µL DSk, 800 µL of buffer pH 7, 178 µg/mL test material
E9: 800 µL DSk, 800 µL of buffer pH 9, 178 µg/mL test material
B4: 800 µL CH3CN, 800 µL of buffer pH 4
B7: 800 µL CH3CN, 800 µL of buffer pH 7
B9: 800 µL CH3CN, 800 µL of buffer pH 9

VERIFICATION WITH ACETIC ACID (ACOH)
To a glass beaker was added deionized water (80 mL), CH3CN (20 mL), NaCl (10 mg), and a stir bar. A pH electrode was immersed in the water (pH meter was previously calibrated at pH 7). The stirrer was started and the stabilized pH was 5.31.
AcOH (100 μL) was added to the stirred water and the stabilized pH was 3.25, which agreed with the calculated pH of 3.27 (based on a pKa of 4.79). These results validated the performance of the pH electrode under these conditions.

TEST MATERIAL ADDITION
To a (clean) glass beaker was added deionized water (80 mL), CH3CN (20 mL), NaCl (10 mg), and a stir bar. The cleaned pH electrode was immersed in the water. The stirrer was started and the stabilized pH was recorded. The test material (100 mg) was added to the stirred water and the pH was recorded every min until stabilized.

Duration of test

Duration of test 1

Duration:

3 h

pH:

4

Temp.:

22 °C

Initial conc. measured:

178 mg/L

Duration of test 2

Duration:

3 h

pH:

7

Temp.:

22 °C

Initial conc. measured:

178 mg/L

Duration of test 3

Duration:

3 h

pH:

9

Temp.:

22 °C

Initial conc. measured:

178 mg/L

Results and discussion

Transformation products:

yes

Identity of transformation products

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

4-chlorophthalic acid

Inventory number:

InventoryMultipleMappingImpl [inventoryEntryValue=EC 201-886-3]

CAS number:

89-20-3

Identity:

1,2-Benzenedicarboxylic acid, 4-chloro-

Molecular formula:

C8H5ClO4

Molecular weight:

200.576

SMILES notation:

OC(=O)c1ccc(Cl)cc1C(=O)O

InChl:

InChI=1/C8H5ClO4/c9-4-1-2-5(7(10)11)6(3-4)8(12)13/h1-3H,(H,10,11)(H,12,13)

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

22 °C

DT50:

< 3 h

Remarks on result:

other: Further investigation of this relatively rapid hydrolysis reaction was not required.

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

22 °C

DT50:

< 3 h

Remarks on result:

other: Further investigation of this relatively rapid hydrolysis reaction was not required.

Dissipation DT50 of parent compound 3

pH:

9

Temp.:

22 °C

DT50:

< 3 h

Remarks on result:

other: Further investigation of this relatively rapid hydrolysis reaction was not required.

Details on results:

No test material was observed in the buffer solutions. The possibility that this loss was due to hydrolysis, and not due to adsorption of the test material onto glass, was supported by the observations that the pH of a water/CH3CN (80/20, v/v) solution of the test material (1 mg/mL) became acidic within minutes of adding the test material to water, and the final pH (2.5) of the solution corresponded to that calculated for the complete conversion of the test material to its hydrolysis product (calculated pH = 2.6).

It was concluded that the test material was hydrolytically unstable at pH 4, pH 7, and pH 9, with a half-life of less than 3 h at 22 °C.
Further investigation of this relatively rapid hydrolysis reaction was not required, based on OECD guidelines that do not require detailed hydrolysis studies on compounds with hydrolysis half-lives less than 24 h at 25 °C (OECD, 1996).

Applicant's summary and conclusion

Validity criteria fulfilled:

not specified

Conclusions:

Under the conditions of this study, it was concluded that the test material was hydrolytically unstable at pH 4, pH 7, and pH 9, with a half-life of less than 3 h at 22 °C.

Executive summary:

The hydrolytic stability of the test material was determined in an OECD 111 study, performed according to GLP. HPLC was used for analytical confirmation. Buffer solutions containing the test material at a concentration of 178 mg/L were prepared at pH 4, 7 and 9. After 3 hours at ambient temperature, solutions were analysed.

Under the conditions of this study, it was concluded that the test material was hydrolytically unstable at pH 4, pH 7, and pH 9, with a half-life of less than 3 h at 22 °C.