1H-Pyrazole-5-carboxylic acid, 3-bromo-1-(3-chloro-2-pyridinyl)-

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2005-11-19 to 2006-05-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to OECD guideline 111 and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Remarks:

Although not required by the guideline a definitive study was performed.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at time of study conduct.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

481-150-8

EC Name:

-

Cas Number:

500011-86-9

Molecular formula:

C9H5BrClN3O2

IUPAC Name:

3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid

Constituent 2

Reference substance name:

DBC80

IUPAC Name:

DBC80

Constituent 3

Reference substance name:

1H-Pyrazole-5-Carboxylic Acid, 3-Bromo-1-(3-Chloro-2-Pyridinyl)-

IUPAC Name:

1H-Pyrazole-5-Carboxylic Acid, 3-Bromo-1-(3-Chloro-2-Pyridinyl)-

Details on test material:

- Name of test material (as cited in study report): IN-DBC80
- Empirical formula: C9H5BrClN3O2
- Molecular weight: 302.52
- Physical state: Tan color powder
- Analytical purity: 96.7 %
- Purity test date: 2005-07-22
- Lot/batch No.: 008
- Expiration date of the lot/batch: 2008-07-22
- Storage condition of test material: In the dark at room temperature (ambient <25 degrees Celcius)

Radiolabelling:

no

Study design

Details on sampling:

- Sampling intervals for the parent/transformation products: 0 hours, 2 hours, 5 hours, 24 hours and 120 hours.
- Sampling method: no data
- Sampling methods for the volatile compounds, if any: no data
- Sampling intervals/times for pH measurements: 0 hours and 120 hours
- Sampling intervals/times for sterility check: 0 hours and 120 hours
- Sample storage conditions before analysis: 20 degrees C +/- 1 degree C

Buffers:

A buffer concentration of 0.01 M was used in order to minimize possible catalytic effects. After preparation, the buffer solutions were filtered by passing through a 0.2-um filter.

BUFFER 1
- pH: 4 (verified pH after sterilization: 3.95)
- Type and final molarity of buffer: 0.01 M Sterile pH 4 Buffer
- Composition of buffer: The buffer was prepared by combining 410 mL of 0.01 M acetic acid solution with 90 of 0.01M sodium acetate solution. Final pH adjustments were made with sodium hydroxide if necessary.

BUFFER 2
- pH: 7 (verified pH after sterilization: 6.98)
- Type and final molarity of buffer: 0.01 M Sterile pH 7 Buffer
- Composition of buffer: The buffer was prepared by adding approximately 195 mL of 0.02 M soidum phosphate (monobasic) and 305 mL of 0.02 M sodium phosphate (dibasic) to a 1000-mL volumetric flask. The contents were diluted with Milipore water, to produce a 0.01 M pH 7.0 phoshate buffer solution. Final pH adjustments were made with hydroxide.

BUFFER 3
- pH: 9 (verified pH after sterilization: 8.97)
- Type and final molarity of buffer: 0.01 M Sterile pH 9 Buffer
- Composition of buffer: A 0.5 M boric acid solution was prepared by transferring 30.9 g of boric acid (61.83 g/mole) to a 1000 mL volumetric flask and diluted it to volume with Millipore water. twenty mL of the 0.5 M boric acid solution was transferred to a 1000 mL volumetric flask and diluted to volume with Millipore water. This 0.01 M boric acid solution was adjusted to pH 9 with 50 5 (w/w) sodium hydroxide solution to produce a 0.01 M pH 9.0 borate buffer solution.

Details on test conditions:

TEST SYSTEM -Individual test systems were composed of sterile buffer containing the test material in separate amber glass vessels with screw caps containing 100 mL of buffer. The individual hydrolysis vessels were then placed in a BOD incubator at 50 degrees C +/- 0.5 degrees C. Each test system was sterilized for a minimum of 121 degrees C at 15 lbs/inches square for 20 minutes prior to the start of the study.

Results and discussion

Preliminary study:

The percent degradation at each tested pH was as follows:
2.2% degredation at ph 4 after 5 days.
1.4% degredation at pH 7 after 5 days.
4.2% degredation at pH9 after 5 days.

Details on results:

The concentration of the test substance in the hydrolysis sterile buffer pH 4 samples (mean of 2 samples) overtime:
0 hours: 0.99 ppm
2 hours: 1.01 ppm
5 hours: 1.03 ppm
24 hours: 1.01 ppm
120 hours: 0.97 ppm

The concentration of the test substance in the hydrolysis sterile buffer pH 7 samples (mean of 2 samples) overtime:
0 hours: 1.01 ppm
2 hours: 1.01 ppm
5 hours: 1.03 ppm
24 hours: 1.02 ppm
120 hours: 0.99 ppm

The concentration of the test substance in the hydrolysis sterile buffer pH 9 samples (mean of 2 samples) overtime:
0 hours: 1.02 ppm
2 hours: 1.03 ppm
5 hours: 1.06 ppm
24 hours: 1.04 ppm
120 hours: 0.98 ppm

Any other information on results incl. tables

Degradation kinetics of the test tubstance were also determined in sterile pH buffers of pH 4, 7, and 9. On the basis of this testing the test substance was shown to be stable to hydrolysis and aqueous abiotic hydrolysis would not be expected to contribute to the degradation significantly at any of the tested pHs.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Based on the results of this study, IN-DBC80 was shown to be hydrolytically stable at pH 4,7, and 9. Hydrolysis will not be a route of degradation in the environment.