Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 4 March 2009 and 29 May 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recently conducted GLP compliant study using the most recent test methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): JKY-214
- Physical state: white solid
- Analytical purity: No information
- Lot/batch No.: Y002E
- Expiration date of the lot/batch: No information
- Stability under test conditions: No information. Assumed stable due to no data to the contrary
- Storage condition of test material: room temperature in the dark
- Other:
Specific details on test material used for the study:
Details on properties of test surrogate or analogue material (migrated information):
none
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products: 0, 2.4, 24, 120, 144
- Sampling method:
The whole sample was passed through a previously primed Strata X (60 mg/ 3 ml) solid phase extraction cartridge. The sample vessel was rinsed with 10 ml of reverse osmosis water, transferring the rinsings to the cartridge and then the cartridge was dried with nitrogen. The analyte was eluted with 5 ml of tetrahydrofuran into a 10 ml volumetric flask and diluted to the mark with reverse osmosis water
- Sampling methods for the volatile compounds, if any: not applicable
- Sampling intervals/times for pH measurements: 0, 2.4, 24, 120, 240
- Sampling intervals/times for sterility check: not applicable
- Sample storage conditions before analysis: not applicable
- Other observation, if any (e.g.: precipitation, color change etc.): none reported
Buffers:

- pH: 4
- Composition of buffer: Potassium hydrogen phthalate; 2.5 mmol/ cubic dm


- pH: 7
- Composition of buffer:
Disodium hydrogen orthophosphate (anhydrous); 1.5 mmol/ cubic dm
Potassium dihydrogen orthophosphate; 1.0mmol/ cubic dm
Sodium chloride; 1.0mmol/ cubic dm

- pH: 9
- Composition of buffer:
Disodium tetraborate; 0.5mmol/ cubic dm
Sodium chloride; 1.0mmol/ cubic dm

The buffer solutions were filtered through a 0.2 pm membrane filter to ensure they were sterile before commencement of the test. Also these solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content
Details on test conditions:
Aliquots (35 ml) of each buffer were transferred to individual glass vessels. Test material dissolved in tetrahydrofuran (1.01 mg/l) was added to each individual sample in the proportion of 1% (i.e. 0.350 ml) to give a nominal concentration of 1.01 x 10"5 g/l in the three buffer solutions.
The solutions were shielded from light whilst maintained at the test temperature.

Preliminary test
Tier 1
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5°C for a period of 144 hours.

Tier 2
Results from the Preliminary test/Tier 1 showed it was not necessary to undertake further testing at pH 4, pH 7 and pH 9.

Results and discussion

Transformation products:
no
Total recovery of test substance (in %)open allclose all
% Recovery:
>= 83.1 - <= 85.4
pH:
4
Temp.:
50 °C
Duration:
6 d
% Recovery:
>= 89.4 - <= 106
pH:
7
Temp.:
50 °C
Duration:
6 d
% Recovery:
>= 85.2 - <= 94.4
pH:
9
Temp.:
50 °C
Duration:
6 d
Dissipation DT50 of parent compoundopen allclose all
pH:
4
Temp.:
25 °C
DT50:
> 1 yr
pH:
7
Temp.:
25 °C
DT50:
> 1 yr
pH:
9
Temp.:
25 °C
DT50:
> 1 yr

Any other information on results incl. tables

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0 to 5.0 x 10 -2mg/l. This was satisfactory with a correlation coefficient of 0.997 being obtained. Recovery of analysis of the sample procedure was assessed and proved adequate for the test.

Applicant's summary and conclusion

Conclusions:
The test substance is considered to be hydrolytically stable and not prone to hydrolysis, with a half life at pH 4,7 and 9 above 1 year at ambient
Executive summary:

The hydrolysis has been assessed using HPLC-MS method according to EU method C7 in compliance with GLP. Measurements for the recovery of test material was calculated by comparison of the recorded peak area of test sample with the recorded peak area of the standards. The test substance is considered to be hydrolytically stable and not prone to hydrolysis, with a half life at pH 4,7 and 9 above 1 year at ambient