Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 Jan 2018 - 29 Jan 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
2016
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
2004
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: White powder
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Remarks:
(by UPLC-UV)
Details on sampling:
PREPARATION OF THE SAMPLES
- The test item was spiked to the buffers to the target concentration of 10 mg/L.
- For each sampling time, duplicate vessels under vacuum were filled with 6 mL test solution.
- The vessels were placed in a temperature controlled environment in the dark.
- Blank buffers containing a similar content of blank spiking solution were treated similarly as the test samples (at t=0).

SAMPLING DETAILS
- Samples for analysis were taken immediately after preparation (t=0) and at t= 5 days.
- Samples taken at t=5 days were cooled to room temperature using running tap water.

pH MEASUREMENTS
The pH of the test solutions (except for the blanks) was determined at each sampling point.
Buffers:
Buffer pH 4: 16.7% 0.1 M sodium acetate and 83.3% 0.1 M acetic acid in water.

Buffer pH 7: 0.1 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide.

Buffer pH 9: 0.1 M boric acid and 0.1 M potassium chloride in water adjusted to pH 9 using 10 N sodium hydroxide.

Details:
- Kind of water: tap water purified by a purification system (Milli-Q, Millipore)
- Sodium azide content: 0.0009% (w/v)


Details on test conditions:
TEST SYSTEM
- Sterilisation method: Each buffer was filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Whatman) and transferred into a sterile vessel.
- Measures to exclude oxygen: nitrogen gas was purged through the sterile buffers for 5 minutes prior to preparation of the blank and test solutions.
- Measures taken to avoid photolytic effects: the test vessels were kept in the dark.

SPIKING SOLUTION
Spiking solution: test substance in acetonitrile. The spiking volume was < 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.

DETAILS TIER 1 STUDY
pH 4.0, pH 7.0 and pH 9.0 at 49.9 ± 0.1°C




Duration of testopen allclose all
Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
10.2 mg/L
Remarks:
Initial conc. measured: see table in Results.
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
10.2 mg/L
Remarks:
Initial conc. measured: see table in Results.
Duration:
5 d
pH:
9
Temp.:
50 °C
Initial conc. measured:
ca. 10.2 mg/L
Remarks:
Initial conc. measured: see table in Results.
Number of replicates:
Two
Positive controls:
no
Negative controls:
no

Results and discussion

Preliminary study:
At pH 4, 7 and pH 9, a degree of hydrolysis < 10% was observed after 5 days at 50°C (half-life time at 25°C is > 1 year).

No further tests were required.
Test performance:
RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- The mean (n=2) recovery at each pH was calculated (see table below).
- The mean recoveries fell within the criterion range of 90-110%.
- Concentrations analysed in the test samples were not corrected for recovery.
Transformation products:
no
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
Remarks on result:
other: actual recovery: 102%
% Recovery:
100
pH:
7
Temp.:
50 °C
Remarks on result:
other: actual recovery: 102%
% Recovery:
100
pH:
9
Temp.:
50 °C
Remarks on result:
other: actual recovery: 101%
Dissipation DT50 of parent compoundopen allclose all
Key result
pH:
4
Temp.:
25 °C
DT50:
> 1 yr
Remarks on result:
hydrolytically stable based on preliminary test
Key result
pH:
7
Temp.:
25 °C
DT50:
> 1 yr
Remarks on result:
hydrolytically stable based on preliminary test
Key result
pH:
9
Temp.:
25 °C
DT50:
> 1 yr
Remarks on result:
hydrolytically stable based on preliminary test

Any other information on results incl. tables

Additional alternative matrices test

- The mean accuracy at each concentration level fell in the range 70-110% (see table below).

- Repeatability at each concentration level: see also table below

Conclusion: the analytical method was accepted for the analysis of the substance in the 3 buffer solutions in the target concentration range of 0.1 – 100 mg/L.

Matrix

Concentration
[mg/L]

Accuracy
[%]

Coefficient of variation
[%]

Target

Nominal

Analyzed

Individual

Mean

Buffer pH 4

0.1

0.100

0.0901

90

90

n.a.

 

 

0.100

0.0905

91

 

 

 

100

100

99.7

100

99

n.a.

 

 

100

98.3

98

 

 

Buffer pH 7

0.1

0.100

0.0887

89

88

1.2

 

 

0.100

0.0868

87

 

 

 

 

0.100

0.0865

86

 

 

 

 

0.100

0.0873

87

 

 

 

 

0.100

0.0888

89

 

 

 

100

100

99.3

99

99

0.90

 

 

100

100

100

 

 

 

 

100

98.0

98

 

 

 

 

100

98.8

99

 

 

 

 

100

100

100

 

 

Buffer pH 9

0.1

0.100

0.0883

88

88

n.a.

 

 

0.100

0.0881

88

 

 

 

100

100

98.7

99

98

n.a.

 

 

100

97.9

98

 

 

n.a.: Not applicable

Table: Tier 1 results:

pH

Sampling time

Analyzed concentration
[mg/L]

Degree of hydrolysis
[%]

pH

Individual

Mean

pH 4

0 hours

10.2

 

 

4.0

 

 

10.2

 

 

4.0

 

5 days

10.1

0.53

0.37

4.0

 

 

10.2

0.22

 

4.0

pH 7

0 hours

10.2

 

 

7.1

 

 

10.2

 

 

7.1

 

5 days

10.1

1.1

0.92

7.1

 

 

10.1

0.70

 

7.1

pH 9

0 hours

10.1

 

 

9.0

 

 

10.2

 

 

9.0

 

5 days

10.0

0.94

1.1

9.0

 

 

10.0

1.3

 

9.0

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
The substance is hydrolytically stable at pH 4, 7 and 9 (half-life time at 25°C: > 1 year).
Executive summary:

The hydrolysis study at pH values normally found in the environment (pH 4, 7 and 9) was performed in a GLP-compliant study according to EC C.7, OECD 111 and EPA OPPTS 835.2120. A degree of < 10% of hydrolysis was observed at pH 4, 7 and 9 after 5 days at 50°C (Tier 1). This corresponds with a half-life time at 25°C of > 1 year. The substance is concluded to be hydrolytically stable at pH 4, 7 and 9.