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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 February 2019 - 27 March 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
2004
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling method preliminary test: Duplicate samples were taken at test start (0 h) and test end (120 h).
- Sampling method definitive test: Duplicate samples were taken at test start (0 h) and at 10 spaced points for pH 4, normally between 10 and 90% of hydrolysis.
The incubation temperature was checked automatically once in an hour and at least once per day manually. The sterility of the test solutions was checked at test end by colony forming units (CFU)-determination with Water Plate Count Agar from additional samples of the definitive test by incubation at 36 ± 1 °C for 48 ± 4 h and at 22 ± 1 °C for 72 ± 4 h.
Buffers:
- Buffer solution pH 4: 0.18 g of sodium hydroxide and 5.7555 g of mono potassium citrate were dissolved in 500 mL purified water.
- Buffer solution pH 7: 3.854 g of ammonium acetate were dissolved in 500 mL purified water.
- Buffer solution pH 9: 0.426 g sodium hydroxide, 1.8638 g potassium chloride and 1.5458 g boric acid were dissolved in 500 mL purified water.

Details on test conditions:
Buffer solutions were prepared from chemicals with analytical grade or better quality, by direct weighing of the buffer components. Buffers were purged with nitrogen for 5 min and then the pH was checked to a precision of at least 0.1 at the test temperatures. Buffers were sterilized by filtration through 0.2 µm.
Duration:
30 d
pH:
4
Temp.:
20 °C
Initial conc. measured:
310 mg/L
Remarks:
definitive test
Duration:
30 d
pH:
4
Temp.:
30 °C
Initial conc. measured:
310 mg/L
Remarks:
definitive test
Duration:
30 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
310 mg/L
Remarks:
definitive test
Duration:
120 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
297 mg/L
Remarks:
preliminary test
Duration:
120 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
301 mg/L
Remarks:
preliminary test
Duration:
120 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
314 mg/L
Remarks:
preliminary test
Number of replicates:
2
Positive controls:
no
Negative controls:
yes
Statistical methods:
For all test conditions the ln concentration vs. time plots have regression graphs with slopes significantly non zero. First order reaction kinetics was applied for data computation. A confirmation of pseudo first order reaction kinetics with coefficients of determination > 0.8 was achieved for the 30 and 50 °C condition. At the 20 °C condition, mainly due to the slow hydrolysis with a resulting low slope of the regression line, this benchmark was not met. Nevertheless, based on the obtained data the pseudo first order reaction kinetics was deemed to be the best fit model for computation of kinetics data.
Preliminary study:
At pH 7 and 9, no significant reduction of the test item concentration was observed (2% and 4%, respectively) and therefore the test item was considered as hydrolytically stable under this condition and a half-life of > 1 year could be assumed for environmental typical temperatures (25 °C). At pH4, 17% degradation was observed after 120 h.
Test performance:
In accordance with OECD TG 111 and EU No Mechod C.7 guideline, the validity criteria of the study is as following:
1) To confirm first order behavior, the regression graph must have a correlation factor of ≥ 0.8. ( In this study, it was 0.443, 0.801 and 0.995 at 20, 30 and 50 ˚C, respectively. Although the correlation factor is not fulfilled at 20 ˚C, it was consideres as accpetable)
2) The test temperature should be within ± 0.5 ˚C of the nominal temperature. (In this study, the temperatures were: 20.0 ± 0.03˚C, 30.0 ± 0.01˚C and 50.0 ± 0.01 ˚C)
3) The pH values of the buffer solutions should be in the range of ± 0.1 pH at test temperature. (This criteria was fulfilled.)
4) Sensitivity of the analytical method should be sufficient to quantify test item concentrations at least down to a 90% reduction of the initial concentration. (This cirteria was fulfilled (LOQ about 6.67%))

Therefore, the study is considered as valid.
Transformation products:
not measured
Key result
pH:
4
Temp.:
20 °C
Hydrolysis rate constant:
0 s-1
DT50:
151 d
Type:
(pseudo-)first order (= half-life)
Key result
pH:
7
Temp.:
50 °C
Remarks on result:
hydrolytically stable based on preliminary test
Key result
pH:
9
Temp.:
50 °C
Remarks on result:
hydrolytically stable based on preliminary test
pH:
4
Temp.:
30 °C
Hydrolysis rate constant:
0 s-1
DT50:
81.3 d
Type:
(pseudo-)first order (= half-life)
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0 s-1
DT50:
12.9 d
Type:
(pseudo-)first order (= half-life)
Details on results:
The test item showed a slow hydrolysis rate (ti/2 > 30 d) for pH 4 at 20 and 30 °C, and a moderate hydrolysis rate (2.4 h < ti/2 30 d) for pH 4 at 50 °C.At pH 7 and 9, no significant reduction of the test item concentration was observed in the preliminary test and therefore the test item was considered as hydrolytically stable under this condition and a half-life of > 1 year could be assumed for environmental typical temperatures (25 °C).

Table 1. Reaction rate constants and half-lives at pH 4

 

pH 4

20 °C

30 °C

50 °C

Slope of regression graph

 

-1.91E-4

 

-3.55E-4

 

-2.24E-3

Correlation factor [r2]

0.443

0.801

0.995

Reaction rate constant

kobs [1/s]

 

5.31E-8

 

9.87E-8

 

6.21E-7

Half-life T½ [h]

3628

1950

310

Confidence interval of half-life T½ [h]

 

2084 to 23822

 

1498 to 2934

 

297 to 323

Half-life T½ [d]

151

81.3

12 .9

Confidence interval of half-life T½ [d]

 

86.8 to 993

 

62.4 to 122

 

12.4 to 13.5

Validity criteria fulfilled:
yes
Conclusions:
The test item showed a slow hydrolysis rate (t1/2 > 30 d) for pH 4 at 20 and 30 °C, and a moderate hydrolysis rate (2.4 h ≤ t1/2 ≤ 30 d) for pH 4 at 50 °C.
At pH 7 and 9, no significant reduction of the test item concentration was observed in the preliminary test and therefore the test item was considered as hydrolytically stable under this condition and a half-life of > 1 year could be assumed for environmental typical temperatures (25 °C).
Executive summary:

The hydrolytic potential of the test substance was investigated in a study in accordance with OECD TG 111 and in compliance with GLP criteria.

In this study, apreliminary test was conducted with the test substance at a concentration of 300 mg/L in buffer solutions at pH 4, 7 and 9 at 50 °C for 5 days. Analyses of the test substance were performed via HPLCDAD on a reversed phase analytical column using the test substance as external standard.

 At pH 7 and 9, no significant reduction of the test item concentration was observed in the preliminary test and therefore the test item was considered as hydrolytically stable under these conditions and a half-life of > 1 year could be assumed at 25 °C. For the pH 4, a definitive test was performed, as a significant reduction (> 10%) of the test item concentration was observed in the preliminary test.

The definitive test was conducted with a test item concentration of 300 mg/L in buffer solution of pH 4 at temperatures of 20, 30 and 50 °C, respectively, for 30 days. Samples were taken at test start (0 h) and at 10 spaced points until test end. Pure test system (buffer solution at pH 4) was analysed at test start and test end and there was no analytical interference with the test item. Reaction rate constants, half-lives and activation energies were calculated from the analysed samples based on a first order reaction kinetics model. The test item showed a slow hydrolysis rate (t1/2> 30 d) for pH 4 at 20 and 30 °C, and a moderate hydrolysis rate (2.4 h ≤ t1/2≤ 30 d) for pH 4 at 50 °C. The hydrolytic DT50 of the test substance at pH 4 and 20 °C was determined to be 151 days.

Description of key information

The test item showed a slow hydrolysis rate (t1/2 > 30 d) for pH 4 at 20 and 30 °C, and a moderate hydrolysis rate (2.4 h ≤ t1/2 ≤ 30 d) for pH 4 at 50 °C.

At pH 7 and 9, no significant reduction of the test item concentration was observed in the preliminary test and therefore the test item was considered as hydrolytically stable under this condition and a half-life of > 1 year could be assumed for environmental typical temperatures (25 °C).

Key value for chemical safety assessment

Additional information

The hydrolytic potential of the test substance was investigated in a study in accordance with OECD TG 111 and in compliance with GLP criteria. In this study, apreliminary test was conducted with the test substance at a concentration of 300 mg/L in buffer solutions at pH 4, 7 and 9 at 50 °C for 5 days. Analyses of the test substance were performed via HPLCDAD on a reversed phase analytical column using the test substance as external standard.

 At pH 7 and 9, no significant reduction of the test item concentration was observed in the preliminary test and therefore the test item was considered as hydrolytically stable under these conditions and a half-life of > 1 year could be assumed at 25 °C.For the pH4, a definitive test was performed, as a significant reduction (> 10%) of the test item concentration was observed in the preliminary test.

The definitive test was conducted with a test item concentration of 300 mg/L in buffer solution of pH 4 at temperatures of 20, 30 and 50 °C, respectively, for 30 days. Samples were taken at test start (0 h) and at 10 spaced points until test end. Pure test system (buffer solution at pH 4) was analysed at test start and test end and there was no analytical interference with the test item. Reaction rate constants, half-lives and activation energies were calculated from the analysed samples based on a first order reaction kinetics model. The test item showed a slow hydrolysis rate (t1/2> 30 d) for pH 4 at 20 and 30 °C, and a moderate hydrolysis rate (2.4 h ≤ t1/2≤ 30 d) for pH 4 at 50 °C. The hydrolytic DT50 of the test substance at pH 4 and 20 °C was determined to be 151 days.

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