2-(4-chlorobenzoyl)benzoic acid

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 12, 2017 to May 17, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

No sample preparation was performed

Buffers:

Buffer solutions:
pH 4.0: 1 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Potassium hydrogen phthalate was diluted to 500 mL with ultrapure water
pH 7.0: 73.9 mL 0.2M Sodium hydroxide and 125 mL 0.2 M Potassium dihydrogen phosphate was diluted to 500 mL with ultrapure water
pH 9.0: 53.5 mL 0.2M Sodium hydroxide and 125 mL 0.2M Boric acid and Potassium chloride was diluted to 500 mL with ultrapure water
These sterile buffer solutions were prepared using reagent grade chemicals and ultrapure, sterile water.

Details on test conditions:

- Test temperature: 49.6-50.3°C
- Hydrolysis was examined at three different pH values: 4, 7 and 9 in the dark.
- The pH of each buffer solution was checked with a calibrated pH meter.
- The hydrolysis reaction was carried out using a dark thermostat to avoid photolytic effects.
- Nitrogen was bubbled into the water before the preparation of the solutions inorder to exclude oxygen.

Duration:

5 d

pH:

4

Initial conc. measured:

ca. 0.187 - ca. 0.188 mg/L

Duration:

5 d

pH:

7

Initial conc. measured:

ca. 0.174 - ca. 0.176 mg/L

Duration:

5 d

pH:

9

Initial conc. measured:

ca. 0.183 - ca. 0.183 mg/L

Number of replicates:

Triplicate

Positive controls:

no

Negative controls:

no

Preliminary study:

In the course of the preliminary test the observed hydrolysis of test substance was less than 10% after 5 d at a temperature of 50±0.5°C at pH 4, 7 and 9. Therefore the test substance is considered to be hydrolytically stable under these circumstances and no additional testing is required.

Test performance:

100 mL sterile solutions were prepared (about 180 μg/mL of test item concentration in each buffer). The solutions were ultrasonicated and filtered on 0.22 μm filter. The pH of each buffer solution was checked with a calibrated pH meter. Solutions were transferred into screw cap tubes. Three from each test solution and one control tubes were prepared. The tubes were thermostated at 49.6-50.3°C. The reaction solutions were analysed at the start of the test and after five days with three replicate samples each. The Day 5 samples were cooled to room temperature. Samples for the start and for the end were diluted with diluent (acetonitrile : ultrapure water = 1: 1) 100 fold, then they were analysed with the above presented HPLC-UV method.

Transformation products:

no

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

Refer to the preliminary test results above.

The hydrolysis test was performed at 49.6-50.3°C, at pH 4, 7 and 9. Measured concentrations and pH values are summarised in below table.

pH	Sampling time, day	Concentration of test substance, μg/mL			Mean of the measured pH
		Results of the separate test vessels	Mean with the 95% confidence intervals (μg/mL)	End/Start, %
4	0 (start)	Control buffer		-	4.01
		188	187 ± 1.13	-	4.01
		187
		187
	5	Control buffer		-	4.00
		187	186 ± 2.19	100	4.01
		187
		185
7	0 (start)	Control buffer		-	7.00
		174	175 ± 3.09	-	6.99
		175
		176
	5	Control buffer		-	7.01
		180	180 ± 0.63	103	7.02
		180
		180
9	0 (start)	Control buffer		-	9.00
		180	180 ± 4.88	-	8.98
		183
		179
	5	Control buffer		-	9.00
		183	183 ± 0.96	102	8.98
		183
		183

Validity criteria fulfilled:

yes

Conclusions:

Under the study conditions, the test substance solution was considered to be hydrolytically stable.

Executive summary:

A study was conducted to determine the hydrolytic stability of the test substance according to OECD Guideline 111 and EU Method C.7, in compliance with GLP. 100 mL sterile solutions were prepared (about 180 μg/mL of test substance) in each buffer pH 4.0, 7.0, 9.0, and were transferred into screw cap tubes. Three from each test solution and one control tubes were prepared. The tubes were thermostated at 49.6-50.3°C. The reaction solutions were analysed at the start of the test and after 5 d with three replicate samples each. The Day 5 samples were cooled to room temperature. Samples for the start and for the end were diluted with diluent (acetonitrile: ultrapure water = 1:1) 100 fold, then they were analysed using HPLC-UV. In the course of the preliminary test, the observed hydrolysis of test substance was less than 10% after 5 d at a temperature of 50±0.5°C and pH 4, 7 and 9. Under the study conditions, the test substance was considered to be hydrolytically stable (Bodnár, 2017).

Additional information

A study was conducted to determine the hydrolytic stability of the test substance according to OECD Guideline 111 and EU Method C.7, in compliance with GLP. 100 mL sterile solutions were prepared (about 180 μg/mL of test substance) in each buffer pH 4.0, 7.0, 9.0, and were transferred into screw cap tubes. Three from each test solution and one control tubes were prepared. The tubes were thermostated at 49.6-50.3°C. The reaction solutions were analysed at the start of the test and after 5 d with three replicate samples each. The Day 5 samples were cooled to room temperature. Samples for the start and for the end were diluted with diluent (acetonitrile: ultrapure water = 1:1) 100 fold, then they were analysed using HPLC-UV. In the course of the preliminary test, the observed hydrolysis of test substance was less than 10% after 5 d at a temperature of 50±0.5°C and pH 4, 7 and 9. Under the study conditions, the test substance was considered to be hydrolytically stable (Bodnár, 2017).