8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Cas Number:

353258-35-2

Molecular formula:

C9H4ClF3N2O2

IUPAC Name:

8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Specific details on test material used for the study:

Test substance: 14C-IN-QEK31-011
Lot #: 1572460
Radiochemical Purity: 97.8%
Specific Activity: 69.12 μCi/mg

Radiolabelling:

yes

Study design

Analytical monitoring:

yes

Duration of test

Duration of test 1

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

2.5 other: μg/mL

Duration of test 2

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

2.5 other: μg/mL

Duration of test 3

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

2.5 other: μg/mL

Number of replicates:

02

Positive controls:

no

Negative controls:

no

Results and discussion

Transformation products:

no

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

The test item is hydrolytically stable, therefore no hydrolysis pathway is proposed.

Total recovery of test substance (in %)

Total recovery of test substance (in %) 1

% Recovery:

>= 104.7 - <= 109.1

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

other: Mass Balance (% AR)

Total recovery of test substance (in %) 2

% Recovery:

>= 107.7 - <= 108.8

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

other: Mass Balance (% AR)

Total recovery of test substance (in %) 3

% Recovery:

>= 106.2 - <= 107.9

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

other: Mass Balance (% AR)

Dissipation DT50 of parent compound

Key result

Remarks on result:

other: The hydrolytic half-life (t1/2) at 25°C is considered to be >1 year at pH 4, 7 and 9

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

This study demonstrated that the test item was hydrolytically stable at pH 4, 7 and 9.
Hydrolysis did not occur across all pH levels tested at 50°C. The hydrolytic half-life (t1/2) at 25°C is considered to be >1 year at pH 4, 7 and 9.

Executive summary:

The hydrolytic stability of the test item was investigated in sterile buffer solutions at pH 4, 7 and 9, which were incubated at 50 ± 0.5°C for 5 days, using 14C-test item

Solutions of 14C-test item were prepared in 0.01 M acetate buffer (pH 4), 0.01 M phosphate buffer (pH 7) and 0.01 M borate buffer (pH 9) at a nominal test concentration of 2.5 μg/mL, which was less than one-half of the solubility of the test item in each of these buffers.

At selected time intervals, samples were analyzed to determine the quantity of radioactivity present in each sample. Radioactivity was quantitatively recovered from each test solution. The material balance of radioactivity throughout the study for all test samples was within the range of 104.7 to 109.1% AR.

Test solutions were subjected to analysis by HPLC to investigate the nature of any hydrolysis products formed. The hydrolysis of the test item at 50 ± 0.5°C after 5 days of incubation was <3% in pH 4, 7 and 9 buffer solutions. Since the applied test item was recovered essentially unchanged after 5 days at 50°C, the test item was considered to be stable {t1/2 at 25°C >1 year} at pH 4, 7 and 9 and no further tests were performed.

Based on the results of this study, hydrolysis is not expected to be a route of degradation of the test item in the environment.