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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 4 October 2000 to 8 December 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
The study is deemed valid although some information were not reported: The product was not identified and the test was done under sterile condition but the method was not reported.
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products:
Preliminary test: pH 4.0, 7.0 and 9.0, temperature = 50°C
Sampling times were 0, 2.4 and 70.3 hours

Test 1: pH pH 4.0, 7.0 and 9.0, temperature = 50°C
Sampling times were:
- 0, 70.3, 74.5, 77, 93.5, 99.5, 101.5, 117.5 and 119.5 hours (pH 4.0) at 50°C
- 0, 6.5, 24, 48 and 72 hours (pH 7.0) at 50°C
- 0, 1, 2.25, 2.5, 3 and 3.5 hours (pH 9.0) at 50°C

Test 3: pH 7.0 and 9.0
Sampling times and temperature of the oven:
- 0, 9, 23, and 25 hours (pH 7.0) at 60°C
- 0, 5, 6, 9 and 23 hours (pH 7.0) at 70°C
- 0, 6, 7, and 9 hours (pH 9.0) at 35°C
- Sampling method: extraction without dilution. Samples were prepared by an extraction with n-heptane (2 mL)
- Sampling intervals/times for pH measurements: pH was measured at each sampling time.
- Sampling intervals/times for sterility check: no data
- Sample storage conditions before analysis: no data
- Other observation, if any (e.g.: precipitation, color change etc.): visual appearance was noted at each sampling time.
Buffers:
- pH 4.0, 7.0, 9.0 buffers were prepared using Titrisol reagents (Merck)
- batch numbersof the reagents: pH 4.0: 00408901; pH 7.0: 00408902; pH 9.0: 90378572
Estimation method (if used):
Not applicable
Details on test conditions:
TEST SYSTEM
- Sterilisation method: the test was done under sterile condition but the method was not reported
- Measures taken to avoid photolytic effects: test bottles protected from light

TEST MEDIUM
- Volume used/treatment: no data
- Kind and purity of water: Deionised water, prepared at CIT using a Milli-Q apparatus (Millipore)
- Preparation of test medium: An aliquot of the test substance was dissolved in 9 mL of methanol and make up to 1000 mL with the buffer solution in a test bottle protected from light.
- Identity of co-solvent: methanol

Duration:
2.4 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
ca. 4.97 mg/L
Duration:
2.4 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
ca. 4.15 mg/L
Duration:
70.3 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
ca. 3.72 mg/L
Duration:
119.5 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
ca. 3.93 mg/L
Duration:
72 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
ca. 4.85 mg/L
Duration:
3.5 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
ca. 4.62 mg/L
Duration:
25 h
pH:
7
Temp.:
60 °C
Initial conc. measured:
ca. 4.5 mg/L
Duration:
23 h
pH:
7
Temp.:
70 °C
Initial conc. measured:
ca. 4.26 mg/L
Duration:
9 h
pH:
9
Temp.:
35 °C
Initial conc. measured:
ca. 4.19 mg/L
Number of replicates:
2
Positive controls:
no
Negative controls:
no
Statistical methods:
Estimation at 25°C:
The values of the Kobs and t1/2 at 25°C for each pH were obtained by extrapolation using Arrhenius plot of Ln k versus 1/T (T expressed in Kelvin) constructed from the data set of test 1 and test 3.
Preliminary study:
The results showed that after 2.4 days, the test substance was hydrolyzed in the conditions of pH tested
at 50°C ± 1°C.
In accordance with the guidelines, the investigations were continued at each pH since more than
10% after 3 days but less than 50% was hydrolyzed after 2.4 hours.
Test 1 was performed in order to determine the nature of the reaction.
Test performance:
The determination was performed in vessels protected from light. No significant variation of pH was observed for any buffer at any time. Resulting solutions at the end of the test were colourless.
Transformation products:
not measured
Details on hydrolysis and appearance of transformation product(s):
Not applicable
% Recovery:
ca. 94
pH:
4
Temp.:
50 °C
Duration:
ca. 119.5 h
% Recovery:
ca. 46
pH:
7
Temp.:
50 °C
Duration:
ca. 72 h
% Recovery:
ca. 34
pH:
9
Temp.:
50 °C
Duration:
ca. 3.5 h
% Recovery:
ca. 42
pH:
7
Temp.:
60 °C
Duration:
ca. 25 h
% Recovery:
ca. 23
pH:
7
Temp.:
70 °C
Duration:
ca. 23 h
% Recovery:
ca. 45
pH:
9
Temp.:
35 °C
Duration:
ca. 9 h
Key result
pH:
4
Temp.:
25 °C
DT50:
> 1 yr
Type:
not specified
Remarks on result:
other: estimated
Key result
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
ca. 0.001 h-1
DT50:
ca. 994 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: estimated
Key result
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
ca. 0.038 h-1
DT50:
ca. 18.1 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: estimated
Other kinetic parameters:
None
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

None

Validity criteria fulfilled:
yes
Conclusions:
At pH 4.0 the test substance can be considered as an hydrolytically stable compound and its t1/2 at +25°C was considered to be greater than 1 year.
At pH 7.0 and pH 9.0 following advanced tests results, the test substance can be considered as hydrolytically unstable with:
Kobs = 0.000697 h-l and t1/2 = 994 hat 25°C for pH 7.0 (estimation)
Kobs = 0.0383 h-1 and t1/2 = 18.1 hat 25°C for pH 9.0 (estimation).
Executive summary:

A study was performed to assess the abiotic degradation of the test substance, according to EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH) with GLP statement.

 

Hydrolysis was evaluated in a preliminary test and then in two main tests. In the first main test the conditions were aqueous buffered solution at pH 4.0, 7.0 and 9.0 at 50°C whereas in the second one the conditions were pH 7.0 / 60°C, pH 7.0 / 70°C and pH 9.0 / 35°C. From this experimental result the estimation of hydrolysis rate constant and half-life were estimated at each pH using the Arrhenius plot of Ln K versus 1/T. The starting concentration was ca. 4 mg/L ± 1 mg/L, a concentration that represented half the saturated concentration in buffer solutions. At each time-point, an aliquot of test solution was prepared by an extraction with n-heptane (2 mL) and the concentration of the test substance was determined by GC-MS.

 

At 25°C, the test substance was found to undergo hydrolysis at pH 7 and 9 only with estimated half-lives of 994 h and 18.1 h, respectively.

Description of key information

EU Method C.7, GLP, key study, validity 2:

Estimated half-life at pH 7 and 25°C = 994 hours.

Estimated half-life at pH 9 and 25°C = 18.1 hours.

Key value for chemical safety assessment

Half-life for hydrolysis:
18.1 h
at the temperature of:
25 °C

Additional information

One key study is available to assess the abiotic degradation of the registered substance, according to EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH) with GLP statement.

Hydrolysis was evaluated in a preliminary test and then in two main tests. In the first main test the conditions were aqueous buffered solution at pH 4.0, 7.0 and 9.0 at 50°C whereas in the second one the conditions were pH 7.0 / 60°C, pH 7.0 / 70°C and pH 9.0 / 35°C. From this experimental result the estimation of hydrolysis rate constant and half-life were estimated at each pH using the Arrhenius plot of Ln K versus 1/T. The starting concentration was ca. 4 mg/L ± 1 mg/L, a concentration that represented half the saturated concentration in buffer solutions. At each time-point, an aliquot of test solution was prepared by an extraction with n-heptane (2 mL) and the concentration of the test substance was determined by GC-MS.

At 25°C, the test substance was found to undergo hydrolysis at pH 7 and 9 only with estimated half-lives of 994 h and 18.1 h, respectively.