1-(3-Chloro-2-pyridinyl)-4,5-dihydro-3-[(phenylsulphonyl)oxy]-1H-pyrazole-5-carboxylic acid ethyl ester

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 2006 - June 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EEC, 1992

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 3-[(benzenesulfonyl)oxy]-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate

EC Number:

846-153-4

Cas Number:

653592-41-7

Molecular formula:

C17H16ClN3O5S

IUPAC Name:

ethyl 3-[(benzenesulfonyl)oxy]-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate

Test material form:

solid

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals:
Duplicate samples were taken from each test system according to the following schedules:
pH 4.0: Samples incubated at 30°C and 40°C: Day 0, Day 1, Day 2, Day 3, Day 5, Day 7, Day 10, Day 20 and Day 30.
pH 7.0: Samples incubated at 20°C: Day 0, Day 0.25, Day 1, Day 2, Day 3, Day 5, Day 10, Day 20 and Day 30.
pH 7.0 Samples incubated at 30°C: Day 0, Day 0.25, Day 1, Day 1.25, Day 2, Day 3, Day 5, Day 10, Day 20 and Day 30.

- Sample storage conditions before analysis:
Samples were analysed immediately after sampling.

Buffers:

- pH:
4.0, 7.0, 9.0
- Composition of buffer:
4.0: 0.01 M acetic acid solution (820 mL) + 0.01 M sodium acetate (180 mL)
7.0: 0.02 M sodium phosphate monobasic solution (195 mL) + 0.02 M sodium phosphate dibasic solution (305 mL) + double distilled water (500 mL)
9.0: 0.5 M boric acid solution (40 mL) + double distilled water (1960 mL)
The pH of the prepared solutions was adjusted by NaoH.

Duration of test

Duration of test 1

Duration:

30 d

pH:

4

Temp.:

30 °C

Initial conc. measured:

0.23 other: μg/mL

Duration of test 2

Duration:

20 d

pH:

4

Temp.:

40 °C

Initial conc. measured:

0.23 other: μg/mL

Duration of test 3

Duration:

30 d

pH:

7

Temp.:

20 °C

Initial conc. measured:

0.26 other: μg/mL

Duration of test 4

Duration:

30 d

pH:

7

Temp.:

30 °C

Initial conc. measured:

0.26 other: μg/mL

Number of replicates:

2 replicates per time point per temperature

Results and discussion

Preliminary study:

Preliminary test:
Sterile buffer solutions at pH 4.0, 7.0, and 9.0 were treated with the test item at approximately 0.25 μg/mL and incubated for 5 days at 50 ± 0.5°C. The hydrolysis after 2.4 hours was 7.7, 4.0 and more than 95% at pH 4.0, 7.0, and 9.0, respectively. The overall hydrolysis of the test item after 5 days was 53.8% for pH 4.0 and more than 95% for pH 7 and 9.
As the hydrolysis at 50 ± 0.5°C after 2.4 hours was >50% at pH 9.0, the test item was considered to be highly unstable (t1/2 at 25°C <1 day) and no further tests were performed. In case of pH 4.0 and 7.0, the degradation of the test item at 50 ± 0.5°C was <50% after 2.4 hours and >10% after 5 days of incubation. Therefore, a definitive test was performed in pH 4.0 buffer solutions (30 and 40°C) and in pH 7.0 buffer solutions (20 and 30°C).

Transformation products:

not measured

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

4

Temp.:

30 °C

Hydrolysis rate constant:

0.05 d-1

DT50:

14 d

Type:

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

Dissipation DT50 of parent compound 2

pH:

4

Temp.:

40 °C

Hydrolysis rate constant:

0.093 d-1

DT50:

7.5 d

Type:

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

Dissipation DT50 of parent compound 3

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

0.148 d-1

DT50:

4.7 d

Type:

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

Remarks on result:

other: Preliminary test

Dissipation DT50 of parent compound 4

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.025 d-1

DT50:

27.6 d

Type:

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

Dissipation DT50 of parent compound 5

pH:

7

Temp.:

30 °C

Hydrolysis rate constant:

0.094 d-1

DT50:

7.4 d

Type:

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

Dissipation DT50 of parent compound 6

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

1.178 d-1

DT50:

0.6 d

Type:

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

Remarks on result:

other: Preliminary test

Applicant's summary and conclusion

Conclusions:

Based on the results of this study, hydrolysis may be a major dissipation route of the test item in the environment at pH 4.0, 7.0 and 9.0.

Executive summary:

This study was conducted to determine the rate of hydrolysis of the test item in sterile buffers of pH 4.0, 7.0, and 9.0. The study was conducted according to EEC Method C.7., Degradation: Abiotic degradation: Hydrolysis as a function of pH (EEC, 1992).
Sterile buffer solutions prepared at pH 4.0, 7.0, and 9.0 were treated with the test item at approximately 25 μg/mL. The pH 4.0, 7.0, and 9.0 sterile buffer samples were incubated for 5 days at 50 ± 0.5°C in the preliminary test. In the definitive test, pH 4.0 sterile buffer samples were incubated for 30 days at 20 ± 0.5°C and at 30 ± 0.5°C. In the definitive test, pH 7.0 sterile buffer samples were incubated for 30 days at 30 ± 0.5°C and for 20 days at 40 ± 0.5°C. Hydrolysis reactions were monitored by analysing the test item concentration at set intervals using HPLC. The HPLC method was validated prior to use for analysis of test solutions.
As the hydrolysis of the test item at 50 ± 0.5°C after 2.4 hours was >50% at pH 9.0, the test item was considered to be highly unstable {t1/2 at 25°C <1 day} and no further tests were performed. According to the definitive test results, the hydrolysis reaction exhibited first-order kinetics at all the test conditions (pH and temperature). The halflife at pH 4.0 / 30°C was 14.0 days and at pH 7.0 / 30°C 7.4 days.

Based on the results of this study, hydrolysis may be a major dissipation route of the test item in the environment at pH 4.0, 7.0 and 9.0.