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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28 September 2016 to 23 November 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
other: Reference to the validated analytical method used for the quantification of the hydrolysis samples.
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
2008
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 (incl. certificate)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- The buffer solutions were filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Whatman) and transferred into sterile vessels.
- To exclude oxygen, nitrogen gas was purged through the solutions for 5 minutes.
- The substance was spiked to the buffer solutions at a target concentration of 2 mg/L using a spiking solution in acetonitrile.
- The spiking volume was < 1% of the sample volume; nominal concentrations were not corrected for the spiking volume.

- For each sampling time, duplicate sterile vessels under vacuum were filled with 6 mL test solution and placed in the dark in a temperature controlled environment.

- Samples for analysis were taken immediately after preparation (t=0) and after 5 days (Tier 1)
- Samples for analysis were taken immediately after preparation (t=0) and at several sampling points after t=0 (Tier 2).
- Samples taken from solutions with a temperature > 20°C were cooled to room temperature using running tap water.

- Blank buffer solutions containing a similar content of blank spiking solution (acetonitrile) were treated similarly as the test samples and analysed at t=0.

- The pH of the test solutions (except for the blanks) was determined at each sampling point.
Buffers:
- Acetate buffer pH 4: aqueous solution of 16.7% 0.1 M sodium acetate and 83.3% 0.1 M acetic acid.
- Phosphate bffer pH 7: aqueous solution of 0.1 M potassium di-hydrogenphosphate adjusted to pH 7 using 10 N sodium hydroxide.
- Borate buffer pH 9: aqueous solution of 0.1 M boric acid and 0.1 M potassium chloride adjusted to pH 9 using 10 N sodium hydroxide.

- Type of water: tap water purified by a purification system




Details on test conditions:
Tier 1 preliminary test at pH 4, 7 and 9 and 49.9 ± 0.1°C.

Tier 2 main study at pH 7 and 9 and different temperatures.
Actual pH and temp.:
-pH 6.9 - 7.0; 19.9 ± 0.3°C, 50.1 ± 0.3°C and 59.8 ± 0.4°C
-pH 9.0 - 9.1; 19.9 ± 0.3°C, 50.3 ± 0.1°C and 60.0 ± 0.1°C

- All solutions containing the substance were protected from light.
Duration:
793.75 h
pH:
7
Temp.:
20 °C
Initial conc. measured:
1.9 mg/L
Remarks:
initial conc. of duplicate samples: 1.90 and 1.90 mg/L
Duration:
793.52 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
1.9 mg/L
Remarks:
initial conc. of duplicate samples: 1.91 and 1.92 mg/L
Duration:
793.3 h
pH:
7
Temp.:
60 °C
Initial conc. measured:
2 mg/L
Remarks:
initial conc. of duplicate samples: 1.93 and 1.98 mg/L
Duration:
510.37 h
pH:
9
Temp.:
20 °C
Initial conc. measured:
1.9 mg/L
Remarks:
initial conc. of duplicate samples: 1.86 and 1.87 mg/L
Duration:
22.23 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
1.9 mg/L
Remarks:
initial conc. of duplicate samples: 1.86 and 1.87 mg/L
Duration:
2.78 h
pH:
9
Temp.:
60 °C
Initial conc. measured:
2 mg/L
Remarks:
initial conc. of duplicate samples: 1.95 and 1.95 mg/L. Concentrations were also analysed at t=73.8 h; because the obtained logarithms relative concentrations were < 0 these results were not used for the calculations.
Number of replicates:
Two
Positive controls:
no
Negative controls:
no
Preliminary study:
A degree of hydrolysis of ≥ 10% was observed at pH 7 after 5 days. As no substance was measured after 5 days at pH 9, this suggest complete hydrolysis of the compound. According to the guideline, the higher Tier test was required to determine the half-life time of the substance at pH 7 and pH 9.

A degree of hydrolysis of < 10% was observed at pH 4 after 5 day (half-life time at 25°C is > 1 year). No further tests were required at pH 4.

Test performance:
RECOVERIES
- Recovery is the concentration analysed at t=0 relative to the nominal concentration.
- The mean recovery was calculated from duplicate samples.
- The mean recoveries at each pH and temperature (Tier 2) are shown below.
- The mean recoveries fell within the criterion range of 90-110%.
- Conclusion: the analytical method was adequate to support the hydrolysis study on the substance.
- Remark: The concentrations analysed in the test samples were not corrected for recovery.
Transformation products:
not specified
% Recovery:
95
pH:
7
Temp.:
20 °C
Duration:
0 h
% Recovery:
96
pH:
7
Temp.:
50 °C
Duration:
0 h
% Recovery:
98
pH:
7
Temp.:
60 °C
Duration:
0 h
% Recovery:
93
pH:
9
Temp.:
20 °C
Duration:
0 h
% Recovery:
93
pH:
9
Temp.:
50 °C
Duration:
0 h
% Recovery:
98
pH:
9
Temp.:
60 °C
Duration:
0 h
Key result
pH:
4
Remarks on result:
hydrolytically stable based on preliminary test
Key result
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0 h-1
DT50:
265 d
Remarks on result:
other: DT50 at 25°C from the Arrhenius equation for 50°C and 60°C
Key result
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
0.009 h-1
DT50:
3.2 d
Remarks on result:
other: DT50 at 25°C from the Arrhenius equation for 20°C, 50°C and 60°C
pH:
7
Temp.:
50 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
13 d
Type:
(pseudo-)first order (= half-life)
pH:
7
Temp.:
60 °C
Hydrolysis rate constant:
0.006 h-1
DT50:
4.6 d
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
20 °C
Hydrolysis rate constant:
0.005 h-1
DT50:
6.2 d
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
50 °C
Hydrolysis rate constant:
0.171 h-1
DT50:
4.1 h
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
60 °C
Hydrolysis rate constant:
0.428 h-1
DT50:
1.6 h
Type:
(pseudo-)first order (= half-life)
Details on results:
No substance was detected in the blank buffer solutions.

Table: Preliminary test (Tier 1) results

pH code

Sampling time

Analysed concentration

[mg/L]

Degree of hydrolysis

[%]

Actual pH

Individual

Mean

 

 

 

 

 

 

pH 4

0 hours

2.00

 

 

4.0

 

 

2.01

 

 

4.0

 

 

 

 

 

 

 

5 days

1.91

4.8

4.4

4.0

 

 

1.93

3.9

 

4.0

 

 

 

 

 

 

pH 7

0 hours

1.99

 

 

7.1

 

 

2.17

 

 

7.1

 

 

 

 

 

 

 

5 days

1.45

30

30

7.0

 

 

1.47

29

 

7.0

 

 

 

 

 

 

pH 9

0 hours

2.05

 

 

9.0

 

 

2.13

 

 

9.0

 

 

 

 

 

 

 

5 days

not detected

not applicable

not applicable

9.0

 

 

not detected

not applicable

 

9.0

Validity criteria fulfilled:
yes
Conclusions:
Half-life time at 25°C and pH 4, pH 7 and pH 9 was determined to be > 1 year, 265 days and 3.2 days, respectively.
Executive summary:

The rate of hydrolysis of the substance at pH values normally found in the environment (pH 4-9) was determined in a GLP-compliant study according to EC C.7, OECD 111 and EPA OPPTS 835.2120.

In the preliminary Tier 1 study, a degree of hydrolysis of < 10% was observed at pH 4 after 5 days at 50°C. This corresponds with a half-life time at 25°C of > 1 year. The substance can be considered hydrolytically stable at pH 4. In the preliminary Tier 1 study, hydrolysis of > 10% was determined at pH 7 and pH 9 after 5 days and 50°C. The Tier 2 study was therefore conducted at pH 7 and pH 9. The substance was shown to degrade by a pseudo-first order behaviour at 50 and 60°C (pH 7) and at 20, 50 and 60°C (pH 9). No hydrolysis occurred at pH 7 and 20°C. The half-life time at 25°C were determined from the Arrhenius equation. The half-life time at 25°C and pH 7 was determined to be 265 days. The half-life time at 25°C and pH 9 was determined to be 3.2 days.

Description of key information

The half-life time of the substance at 25°C and pH 4, pH 7 and pH 9 was determined to be > 1 year, 265 days and 3.2 days, respectively.

Key value for chemical safety assessment

Half-life for hydrolysis:
265 d
at the temperature of:
25 °C

Additional information