Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-09-27 to 2007-04-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guideline 111 (Hydrolysis as a Function of pH) and EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH) without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
: Certificate issued by the United Kingdom GLP monitoring authorities.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): VRT-753136 hcl
- Molecular formula (if other than submission substance): not applicable
- Molecular weight (if other than submission substance): not applicable
- Smiles notation (if other than submission substance): not applicable
- InChl (if other than submission substance): not applicable
- Structural formula attached as image file (if other than submission substance): not applicable
- Substance type: no data
- Physical state: white powder
- Analytical purity: 99.4% w/w by High Performance Liquid Chromatography (HPLC)
- Impurities (identity and concentrations): individual unknown components were detected at 0.03 area%; isopropanol (residual solvent) at 300 ppm
- Composition of test material, percentage of components: not applicable
- Isomers composition: not applicable
- Purity test date: 2006-05-25
- Lot/batch No.: 25515
- Expiration date of the lot/batch: May 2008
- Stability under test conditions: no data
- Storage condition of test material: at room temperature
- Other: no data
Specific details on test material used for the study:
Details on properties of test surrogate or analogue material (migrated information):
Not applicable
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products: approx. 5 min, 2.4 and 120 h
- Sampling method: At each sampling time, an aliquot (1 mL) was diluted to volume (10 mL) with mobile phase for analysis by high performance liquid chromatography (HPLC).
- Sampling methods for the volatile compounds, if any: not applicable
- Sampling intervals/times for pH measurements: 0 and 120 h
- Sampling intervals/times for sterility check: not applicable
- Sample storage conditions before analysis: no data
- Other observation, if any: no data
Buffers:
- pH: 4, 7, 9
- Type and final molarity of buffer: phosphate (pH 4 and 7) and borate (pH 9); no molarity provided
- Composition of buffer:
- pH 4.0 : Potassium dihydrogen orthophosphate (6.0 g) and disodium hydrogen orthophosphate dodecahydrate (12.8 g) were dissolved in purified water (1900 mL), and the pH was adjusted to 4.0 ± 0.05 with orthophosphoric acid. The volume was then adjusted to 2000 mL with purified water.
- pH 7.0 : Potassium dihydrogen orthophosphate (27.2 g) was dissolved in purified water (3800 mL), 1M sodium hydroxide (120 mL) was added and the pH was adjusted to 7.0 ± 0.05 with 1M hydrochloric acid. The volume was then adjusted to 4000 mL with purified water.
- pH 9.0 : Disodium tetraborate decahydrate (66.4 g) and potassium dihydrogen orthophosphate (7.2 g) were dissolved in purified water (3800 mL); and the pH was adjusted to 9.0 ± 0.05 with 1M hydrochloric acid. The volume was then adjusted to 4000 mL with purified water.
Estimation method (if used):
Not applicable
Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Wheaton vials, 100 mL
- Sterilisation method: no data
- Lighting: test was performed in the dark
- Measures taken to avoid photolytic effects: incubation performed in the dark
- Measures to exclude oxygen: The test vials were purged of oxygen with nitrogen.
- Details on test procedure for unstable compounds: not applicable
- Details of traps for volatile, if any: not applicable
- If no traps were used, is the test system closed/open: no data
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no data


TEST MEDIUM
- Volume used/treatment: 100 mL (90 mL buffer, 10 mL test solution)
- Kind and purity of water: purified water
- Preparation of test medium: no data
- Renewal of test solution: none
- Identity and concentration of co-solvent: not applicable


OTHER TEST CONDITIONS
- Adjustment of pH: no data
- Dissolved oxygen: no data
Duration of testopen allclose all
Duration:
120 h
pH:
4
Initial conc. measured:
1.07 g/L
Duration:
120 h
pH:
7
Initial conc. measured:
1.07 g/L
Duration:
120 h
pH:
9
Initial conc. measured:
1.07 g/L
Number of replicates:
2
Positive controls:
no
Negative controls:
no
Statistical methods:
no data

Results and discussion

Preliminary study:
- Results from the preliminary investigation showed that there was no significant change in the concentration of the test substance when incubated in pH 4, 7 and 9 buffer solutions at 50 ± 0.5 deg C (see Table 2). Less than 10% hydrolysis had occurred after 120 hours (5 days) under these conditions, equivalent to a half-life of greater than 1 year under environmental conditions (25 deg C).
Test performance:
- The pH was within 0.1 units of the target buffer pHs at the beginning and end of the 120 h incubation.
- The test temperature was maintained within 0.5 deg C of the target temperature.
Transformation products:
not measured
Details on hydrolysis and appearance of transformation product(s):
Not applicable
Total recovery of test substance (in %)open allclose all
% Recovery:
100
pH:
4
Temp.:
50 °C
Duration:
120 h
% Recovery:
100
pH:
7
Temp.:
50 °C
Duration:
120 h
% Recovery:
100
pH:
9
Temp.:
50 °C
Duration:
120 h
Dissipation DT50 of parent compound
Temp.:
25 °C
DT50:
> 1 yr
Type:
not specified
Remarks on result:
other: Less than 10% hydrolysis had occurred after 120 hours at pH 4, 7 and 9, equivalent to a half-life >1 year under environmental conditions (25 deg C).
Other kinetic parameters:
no data
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: yes, except for sterility which was confirmed
- Anomalies or problems encountered (if yes): not applicable

MAJOR TRANSFORMATION PRODUCTS
- Not applicable

MINOR TRANSFORMATION PRODUCTS
- Not applicable

MINERALISATION
- Not applicable

INDICATION OF UNSTABLE TRANSFORMATION PRODUCTS:
- Not applicable

VOLATILIZATION
- Not applicable

UNIDENTIFIED RADIOACTIVITY
- Not applicable

PATHWAYS OF HYDROLYSIS
- Not applicable

SUPPLEMENTARY EXPERIMENT
- Not applicable

Any other information on results incl. tables

Table 1. Concentration of the test substance in solution at each sampling time in g/L.

0 h 0 h 2.4 h 2.4 h 120 h 120 h
pH Measured Mean Measured Mean Measured Mean
4 1.07, 1.07 1.07 1.07, 1.08 1.07 1.08, 1.07 1.07
7 1.07, 1.07 1.07 1.08, 1.08 1.08 1.06, 1.07 1.07
9 1.05, 1.08 1.07 1.09, 1.13 1.11 1.08, 1.09 1.08

Applicant's summary and conclusion

Conclusions:
Less than 10% hydrolysis had occurred after 120 hours (5 days) under these conditions, equivalent to a half-life of greater than 1 year under environmental conditions (25 deg C). Therefore, the test substance was determined to be hydrolytically stable under acidic, neutral and basic conditions.
Executive summary:

Not applicable