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EC number: 701-003-6 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Hydrolysis
Administrative data
Link to relevant study record(s)
- Endpoint:
- hydrolysis
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06 September 2016 to 19 May 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
- Version / remarks:
- European Community (EC), EC no. 440/2008, Part C: Methods for the Determination of Ecotoxicity, Guideline C.7: “Degradation - Abiotic Degradation: Hydrolysis as a Function of pH”, Official Journal of the European Union no. L142, May 31, 2008.
- Deviations:
- yes
- Remarks:
- See "any other information" for details
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 111 (Hydrolysis as a Function of pH)
- Version / remarks:
- Organization for Economic Co-operation and Development (OECD), OECD Guidelines for the Testing of Chemicals no. 111: “Hydrolysis as a Function of pH", April 13, 2004.
- Deviations:
- yes
- Remarks:
- See "Any other information" for details
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)
- Version / remarks:
- United States Environmental Protection Agency (EPA), Fate, Transport and Transformation Test Guidelines no. OPPTS 835.2120: "Hydrolysis", October 2008.
- Deviations:
- yes
- Remarks:
- See "Any other information" for details.
- GLP compliance:
- yes
- Specific details on test material used for the study:
- No further details specified in the study report.
- Radiolabelling:
- no
- Analytical monitoring:
- yes
- Details on sampling:
- Preliminary test - Tier 1
The concentration of the test item in the test samples was determined immediately after preparation (t=0), after 2.4 hours and after 5 days. The samples taken at t=2.4 hours and at t=5 days were cooled to room temperature using running tap water. The samples were diluted in a 1:3 (v:v) ratio with methanol and analysed.
Main study - Tier 2
The concentrations of the test item were determined immediately after preparation (t=0) and at several sampling points after t=0. - Buffers:
- Acetate buffer pH 4, 0.01 M: solution of 16.7% 0.01 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. The buffer contains 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.01 M: solution of 0.01 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.
Borate buffer pH 9, 0.01 M: solution of 0.01 M boric acid in water and 0.01 M potassium chloride in water adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide. - Details on test conditions:
- Performance of the study
The rate of hydrolysis of the test item as a function of pH was determined at pH values normally found in the environment (pH 4-9).
Preliminary test - Tier 1
The buffer solutions were filter-sterilised through a 0.2 μm FP 30/0.2 CA-S filter (Whatman, Dassel, Germany) and transferred into a sterile vessel. To exclude oxygen, nitrogen gas was purged through the solution for 5 minutes. The test item was spiked to the solutions at a target concentration of 200 μg/L using a spiking solution in methanol. 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 at 49.6°C ± 0.2°C.
Note: the spiking volume was < 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.
The concentration of the test item in the test samples was determined immediately after preparation (t=0), after 2.4 hours and after 5 days. The samples taken at t=2.4 hours and at t=5 days were cooled to room temperature using running tap water. The samples were diluted in a 1:3 (v:v) ratio with methanol and analysed.
Blank buffer solutions containing a similar content of blank spiking solution were treated similarly as the test samples and analysed at t=0.
The pH of each of the test solutions (except for the blanks) was determined at each sampling time.
Main study - Tier 2
Test samples were prepared and treated similarly as during the preliminary test.
The concentrations of the test item were determined immediately after preparation (t=0) and at several sampling points after t=0.
Blank buffer solutions were treated similarly as the test samples and analysed at t=0.
The pH of each of the test solutions (except for the blanks) was determined at least at the beginning and at the end of the test.
Identification of hydrolysis products – Tier 3
Tests at 20, 50 and 60 °C showed that the decrease in concentration observed is most probably due to adsorption or limited solubility and not due to hydrolysis. Therefore Tier 3 testing was not applicable. - Duration:
- 30 d
- pH:
- 4
- Temp.:
- 20 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 7
- Temp.:
- 20 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 9
- Temp.:
- 20 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 4
- Temp.:
- 50 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 7
- Temp.:
- 50 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 9
- Temp.:
- 50 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 4
- Temp.:
- 60 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 7
- Temp.:
- 60 °C
- Initial conc. measured:
- 200 µg/L
- Duration:
- 30 d
- pH:
- 9
- Temp.:
- 60 °C
- Initial conc. measured:
- 200 µg/L
- Number of replicates:
- 2 replicates per pH level and per temperature
- Positive controls:
- no
- Negative controls:
- no
- Statistical methods:
- See "Any other information" for statistical methods and formulas.
- Preliminary study:
- Preliminary test - Tier 1
A decrease in concentration of ≥ 10% was observed at pH 4, pH 7 and pH 9 after 5 days.
According to the guideline, the higher Tier test was required if a reduction of >10% is observed to determine the half-life time of the test item.
A small peak at the retention time of the test item was detected in the chromatograms of the blank buffer solutions. Maximum contribution to the test solutions at start of the test was <1% based on peak area and therefore considered negligible.
The mean recovery of the test item containing buffer solutions at pH 4 at t=0 fell outside the criterion range of 70-110%. Because hydrolysis is calculated using the relative concentration, the slightly low recovery at pH 4 has no effect on the outcome of the study. The mean recoveries of the test item containing buffer solutions at pH 7 and pH 9 at t=0 fell within the criterion range of 70-110%. - Transformation products:
- not specified
- Key result
- pH:
- 4
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0 h-1
- DT50:
- 9 249 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 7
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- -0 h-1
- DT50:
- -1 687 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 9
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- -0.001 h-1
- DT50:
- -47 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 4
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.001 h-1
- DT50:
- 20 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 7
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.002 h-1
- DT50:
- 18 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 9
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.002 h-1
- DT50:
- 18 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 4
- Temp.:
- 60 °C
- Hydrolysis rate constant:
- 0.002 h-1
- DT50:
- 18 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 7
- Temp.:
- 60 °C
- Hydrolysis rate constant:
- 0.001 h-1
- DT50:
- 33 d
- Type:
- (pseudo-)first order (= half-life)
- Key result
- pH:
- 9
- Temp.:
- 60 °C
- Hydrolysis rate constant:
- 0.001 h-1
- DT50:
- 45 d
- Type:
- (pseudo-)first order (= half-life)
- Details on results:
- Preliminary test - Tier 1
A decrease in concentration of ≥ 10% was observed at pH 4, pH 7 and pH 9 after 5 days.
According to the guideline, the higher Tier test was required if a reduction of >10% is observed to determine the half-life time of the test item.
A small peak at the retention time of the test item was detected in the chromatograms of the blank buffer solutions. Maximum contribution to the test solutions at start of the test was <1% based on peak area and therefore considered negligible.
The mean recovery of the test item containing buffer solutions at pH 4 at t=0 fell outside the criterion range of 70-110%. Because hydrolysis is calculated using the relative concentration, the slightly low recovery at pH 4 has no effect on the outcome of the study. The mean recoveries of the test item containing buffer solutions at pH 7 and pH 9 at t=0 fell within the criterion range of 70-110%.
Main study - Tier 2
pH 4
No test item was detected in the blank buffer solutions. The responses observed in some blanks were smaller than the responses in analytical blanks analysed in the same series.
The mean recovery of the of the test item containing buffer solutions at t=0 fell outside the criterion range of 70-110%. Because hydrolysis is calculated using the relative concentration, the low recovery has no effect on the outcome of the study.
For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. At all temperatures linear relationships were obtained though the correlation coefficient for the test at 20 °C was poor.
The half-life times of the test item were determined according to the model for pseudo-first order reactions. Logarithms of the relative concentrations were correlated with time using linear regression analysis.
The rate constant (kobs) and half-life time of the test item at each temperature was obtained and the Arrhenius equation was used to determine the rate constant and half-life time at 25 °C.
These results however are not as expected for hydrolysis. For hydrolysis, rate constants and slopes increase by a factor 2 to 3 with a 10 °C increase in temperature. This was not observed.
Based on the relatively low recovery at start of the tests and the steep decrease in concentration during the first hours of the tests at 50 and 60 °C, it is expected that the decrease in concentration observed in the various tests at pH 4 is most probably due to adsorption and/or limited solubility and not due to hydrolysis. The amide bond in the various compounds present in MLA-3202 is expected to be stable at pH 4.
pH 7
No test item was detected in the blank buffer solutions. The responses observed in some blanks were smaller than the responses in analytical blanks analysed in the same series.
In the test at 20 °C, the mean recovery of the test item containing buffer solutions at t=0 fell outside the criterion range of 70-110%. Because hydrolysis is calculated using the relative concentration, low recovery has no effect on the outcome of the study. In the tests at 50 and 60 °C, the mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 70-110%.
For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. At all temperatures linear relationships were obtained though the correlation coefficient for the tests at 20 and 60 °C was poor.
The half-life times of the test item were determined according to the model for pseudo-first order reactions. Logarithms of the relative concentrations were correlated with time using linear regression analysis.
The rate constant (kobs) and half-life time of the test item at each temperature was obtained and the Arrhenius equation was used to determine the rate constant and half-life time at 25 °C.
These results however are not as expected for hydrolysis. For hydrolysis, rate constants and slopes increase by a factor 2 to 3 with a 10 °C increase in temperature. This was not observed.
Even a negative half-life time was obtained at 20 °C due to a slight increase of concentration with time which is not possible in case of hydrolysis.
Based on the relatively low recovery at start of the tests and the steep decrease in concentration during the first hours of the tests at 50 and 60 °C, it is expected that the decrease in concentration observed in the various tests at pH 7 is most probably due to adsorption and/or limited solubility and not due to hydrolysis. The amide bond in the various compounds present in MLA-3202 is expected to be stable at pH 7.
pH 9
No test item was detected in the blank buffer solutions. The responses observed in some blanks were smaller than the responses in analytical blanks analysed in the same series.
In the test at 20 °C, the mean recovery of the test item containing buffer solutions at t=0 fell outside the criterion range of 70-110%. Because hydrolysis is calculated using the relative concentration, low recovery has no effect on the outcome of the study. In the tests at 50 and 60 °C, the mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 70-110%.
For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. At all temperatures linear relationships were obtained though the correlation coefficient for the tests at 20 and 60 °C was poor.
The half-life times of the test item were determined according to the model for pseudo-first order reactions. Logarithms of the relative concentrations were correlated with time using linear regression analysis.
The rate constant (kobs) and half-life time of the test item at each temperature was obtained and the Arrhenius equation was used to determine the rate constant and half-life time at 25 °C.
These results however are not as expected for hydrolysis. For hydrolysis, rate constants and slopes increase by a factor 2 to 3 with a 10 °C increase in temperature. This was not observed.
Even a negative half-life time was obtained at 20 °C due to a slight increase of concentration with time which is not possible in case of hydrolysis.
Based on the relatively low recovery at start of the tests and the steep decrease in concentration during the first hours of the tests at 50 and 60 °C, it is expected that the decrease in concentration observed in the various tests at pH 9 is most probably due to adsorption and/or limited solubility and not due to hydrolysis. The amide bond in the various compounds present in MLA-3202 is expected to be stable at pH 9. - Results with reference substance:
- Reference substance not utilised in this study.
- Validity criteria fulfilled:
- yes
- Conclusions:
- Hydrolysis at pH 4, pH 7 and pH 9: Tests at 20, 50 and 60 °C showed that the decrease in concentration observed is most probably due to adsorption or limited solubility in the buffer solution and not due to hydrolysis.
- Executive summary:
The purpose of the study was to determine the following physico-chemical properties for MLA-3202:
-Hydrolysis as a function of pH
The study was performed in accordance with the following guidelines:
European Community (EC), EC no. 440/2008, Part C: Methods for the Determination of Ecotoxicity, Guideline C.7: “Degradation - Abiotic Degradation: Hydrolysis as a Function of pH”, Official Journal of the European Union no. L142, May 31, 2008.
Organization for Economic Co-operation and Development (OECD), OECD Guidelines for the Testing of Chemicals no. 111: “Hydrolysis as a Function of pH", April 13, 2004.
United States Environmental Protection Agency (EPA), Fate, Transport and Transformation Test Guidelines no. OPPTS 835.2120: "Hydrolysis", October 2008.
The rate of hydrolysis of the test item as a function of pH was determined at pH values normally found in the environment (pH 4-9).
The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of MLA-3202 at pH values normally found in the environment (pH 4-pH 9).
The half-life times of the test item were:
pH 4
pH 7
pH 9
Temperature
[°C]
t½
[days]
Temperature
[°C]
t½
[days]
Temperature
[°C]
t½
[days]
20
50
60
9249
20
18
20
50
60
-1687
18
33
20
50
60
-47
18
45
These results however are not as expected for hydrolysis. For hydrolysis, rate constants and slopes increase by a factor 2 to 3 with a 10 °C increase in temperature. This was not observed.
Even a negative half-life time was obtained at 20 °C at pH 7 and pH 9 due to a slight increase of concentration with time which is not possible in case of hydrolysis.
Based on the relatively low recovery at start of the tests and the steep decrease in concentration during the first hours of the tests at 50 and 60 °C, it is expected that the decrease in concentration observed in the various tests at pH 4, pH 7 and pH 9 is most probably due to adsorption and/or limited solubility in the buffer solutions and not due to hydrolysis. The amide bond in the various compounds present in MLA-3202 is expected to be stable at pH 4, pH 7 and pH 9.
Reference
Preliminary test – hydrolysis of the test item at pH 4, pH 7 and pH 9
pH code |
Sampling time |
Analysed concentration1 [μg/L] |
Degree of hydrolysis [%] |
Actual pH |
|
Individual |
Mean |
||||
pH 4 |
0 hours
2.4 hours
5 days |
119 131
66.2 79.1
33.9 34.2 |
47 37
73 73 |
42
73 |
4.1 4.1
4.1 4.1
4.2 4.2 |
pH 7 |
0 hours
2.4 hours
5 days |
170 166
88.1 86.4
41.7 38.7 |
48 49
75 77 |
48
76 |
7.0 7.0
7.0 7.0
7.0 7.0 |
pH 9 |
0 hours
2.4 hours
5 days |
170 167
116 105
56.9 43.6 |
31 38
66 74 |
34
70 |
9.2 9.2
9.2 9.2
9.2 9.2 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Recoveries
pH code |
Nominal concentration1 [μg/L] |
Analysed concentration [μg/L] |
Recovery [%] |
Mean recovery [%] |
pH 4 |
200 200 |
119 131 |
60 66 |
63 |
pH 7 |
200 200 |
170 166 |
85 83 |
84 |
pH 9 |
200 200 |
170 167 |
85 84 |
84 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Main test – hydrolysis of the test item at pH 4 and 20 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 21.65 21.65 46.12 46.12 48.17 48.17 50.20 50.20 143.80 143.80 213.55 213.55 287.75 287.75 455.78 455.78 551.93 551.93 626.42 626.42 721.97 721.97 |
121 119 56.1 52.2 61.8 71.4 75.7 92.4 60.5 81.0 77.3 82.6 59.7 58.9 73.1 73.0 66.6 63.9 63.1 61.9 70.3 62.5 67.3 82.2 |
101 99 47 43 51 59 63 77 50 67 64 69 50 49 61 61 55 53 53 52 58 52 56 68 |
2.00 2.00 1.67 1.64 1.71 1.77 1.80 1.89 1.70 1.83 1.81 1.84 1.70 1.69 1.78 1.78 1.74 1.73 1.72 1.71 1.77 1.72 1.75 1.84 |
4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.0 4.0 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Main test – hydrolysis of the test item at pH 4 and 50 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 2.03 2.03 3.12 3.12 22.67 22.67 27.67 27.67 48.05 48.05 72.28 72.28 98.67 98.67 169.202 169.202 215.85 215.85 261.82 261.82 335.80 335.80 406.03 406.03 503.78 503.78 720.95 720.95 |
109 104 55.0 71.9 61.4 80.2 56.3 46.3 45.6 47.8 42.4 43.7 38.0 37.9 33.7 35.6 28.6 31.0 26.2 28.1 24.4 26.8 23.9 24.3 21.1 17.4 15.2 19.4 15.3 15.0 |
102 98 52 68 58 75 53 44 43 45 40 41 36 36 32 33 27 29 25 26 23 25 22 23 20 16 14 18 14 14 |
2.01 1.99 1.71 1.83 1.76 1.88 1.72 1.64 1.63 1.65 1.60 1.61 1.55 1.55 1.50 1.52 1.43 1.46 1.39 1.42 1.36 1.40 1.35 1.36 1.30 1.21 1.16 1.26 1.16 1.15 |
4.1 4.0 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.2 4.2 4.2 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
2 Due to a technical problem with the UPLC, samples taken and pretreated on 27 Feb 2017 had to be stored overnight at room temperature in the autosampler until analysis on 28 Feb 2017.
Main test – hydrolysis of the test item at pH 4 and 60 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 24.08 24.08 45.75 45.75 120.15 120.15 288.00 288.00 384.18 384.18 458.70 458.70 626.95 626.95 722.62 722.62 |
131 131 96.5 98.5 69.9 82.6 73.0 72.3 52.7 57.7 43.4 44.7 41.1 39.7 36.0 36.1 31.2 38.3 |
100 100 74 75 53 63 56 55 40 44 33 34 31 30 28 28 24 29 |
2.00 2.00 1.87 1.88 1.73 1.80 1.75 1.74 1.60 1.64 1.52 1.53 1.50 1.48 1.44 1.44 1.38 1.47 |
4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.0 4.1 4.0 4.0 4.1 4.1 4.1 4.1 4.1 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Recoveries at pH 4
Temperature (°C) |
Nominal concentration1 [μg/L] |
Analysed concentration [μg/L] |
Recovery [%] |
Mean recovery [%] |
20 |
200 200 |
121 119 |
60 60 |
60 |
50 |
200 200 |
109 104 |
54 52 |
53 |
60 |
200 200 |
131 131 |
65 66 |
65 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Statistical parameters of the regression curves at pH 4
Temperature (°C) |
Slope [hours-1] |
Intercept |
Coefficient of correlation |
20
50
60
|
-1.36 x 10-6
-6.31 x 10-4
-7.10 x 10-4 |
1.75
1.56
1.86 |
0.0055
0.95
0.93 |
Rate constants (kobs) and half-life time (t½) at pH 4
Temperature [°C] |
kobs [hours-1] |
t½ [days] |
20
50
60
|
3.12 x 10-6
1.45 x 10-3
1.64 x 10-3 |
9249
20
18 |
Main test – hydrolysis of the test item at pH 7 and 20 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 21.37 21.37 45.83 45.83 47.88 47.88 49.92 49.92 143.52 143.52 213.27 213.27 287.47 287.47 455.50 455.50 551.65 551.65 626.13 626.13 721.68 721.68 |
131 128 68.0 64.9 72.9 78.6 75.8 76.2 77.8 69.7 70.2 74.3 43.4 42.6 330 40.7 29.5 36.4 49.2 44.9 39.8 36.8 39.7 39.0 |
101 99 53 50 56 61 59 59 60 54 54 57 34 33 25 361 23 28 38 35 31 28 31 30 |
2.01 1.99 1.72 1.70 1.75 1.78 14.77 1.77 1.78 1.73 1.73 1.76 1.53 1.52 1.41 1.50 1.36 1.45 1.58 1.54 1.49 1.45 1.49 1.48 |
7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.0 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Main test – hydrolysis of the test item at pH 7 and 50 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 1.63 1.63 2.72 2.72 22.27 22.27 27.27 27.27 47.65 47.65 71.88 71.88 98.27 98.27 168.802 168.802 215.45 215.45 261.42 261.42 335.40 335.40 405.63 405.63 503.37 503.37 720.55 720.55 |
143 143 85.8 89.7 90.7 89.0 67.0 62.5 59.2 53.3 48.8 49.1 42.0 52.6 46.6 45.2 33.9 37.0 31.8 31.3 29.4 37.4 29.2 30.2 25.5 23.9 19.6 23.0 17.1 16.7 |
100 100 60 63 63 62 47 44 41 37 34 34 30 37 33 32 24 26 22 22 21 26 20 21 18 17 14 16 12 12 |
2.00 2.00 1.78 1.80 1.80 1.79 1.67 1.64 1.62 1.57 1.53 1.54 1.47 1.57 1.51 1.50 1.37 1.41 1.35 1.34 1.31 1.42 1.31 1.33 1.25 1.22 1.14 1.21 1.08 1.07 |
7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.1 7.1 7.1 7.1 7.0 7.0 7.1 7.1 7.1 7.1 7.1 7.0 7.0 7.1 7.0 7.0 7.1 7.0 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
2 Due to a technical problem with the UPLC, samples taken and pretreated on 27 Feb 2017 had to be stored overnight at room temperature in the autosampler until analysis on 28 Feb 2017.
Main test – hydrolysis of the test item at pH 4 and 60 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 23.38 23.38 45.05 45.05 119.45 119.45 287.30 287.30 383.48 383.48 458.00 458.00 626.25 626.25 721.92 721.92 |
142 142 82.6 84.7 75.9 65.1 82.9 87.7 74.5 55.6 80.3 82.3 57.7 54.2 12.6 53.6 70.2 63.7 |
100 100 58 60 54 46 58 62 53 39 57 58 41 38 8.9 38 50 45 |
2.00 2.00 1.77 1.78 1.73 1.66 1.77 1.79 1.72 1.59 1.75 1.76 1.61 1.58 0.952 1.58 1.69 1.65 |
7.0 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 7.1 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
2Outlier; not used for further calculations.
Recoveries at pH 7
Temperature (°C) |
Nominal concentration1 [μg/L] |
Analysed concentration [μg/L] |
Recovery [%] |
Mean recovery [%] |
20 |
200 200 |
131 128 |
66 64 |
65 |
50 |
200 200 |
143 143 |
72 71 |
72 |
60 |
200 200 |
142 142 |
71 71 |
71 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Statistical parameters of the regression curves at pH 7
Temperature (°C) |
Slope [hours-1] |
Intercept |
Coefficient of correlation |
20
50
60
|
7.43 x 10-6
-7.05 x 10-4
-3.78 x 10-4 |
1.48
1.55
1.77 |
0.023
0.96
0.43 |
Rate constants (kobs) and half-life time (t½) at pH 7
Temperature [°C] |
kobs [hours-1] |
t½ [days] |
20
50
60
|
-1.71 x 10-5
1.62 x 10-3
8.71 x 10-4 |
-1687
18
33 |
Main test – hydrolysis of the test item at pH 9 and 20 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 19.80 19.80 44.27 44.27 46.32 46.32 48.35 48.35 141.95 141.95 211.70 211.70 285.90 285.90 453.93 453.93 550.08 550.08 624.57 624.57 720.12 720.12 |
138 140 78.6 77.8 82.1 92.7 93.3 91.3 87.4 89.2 96.9 98.2 27.2 19.9 28.0 25.7 28.8 24.4 32.4 34.3 30.9 25.2 32.6 35.6 |
100 100 57 56 69 67 67 66 63 64 70 71 20 14 20 19 21 18 23 25 22 18 23 26 |
2.00 2.00 1.75 1.75 1.77 1.82 1.83 1.82 1.80 1.81 1.84 1.85 1.29 1.16 1.30 1.28 1.32 1.25 1.37 1.39 1.35 1.26 1.37 1.41 |
9.0 9.0 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 9.0 9.0 9.0 9.0 8.9 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Main test – hydrolysis of the test item at pH 9 and 50 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 1.10 1.10 2.18 2.18 21.73 21.73 26.73 26.73 47.12 47.12 71.35 71.35 97.73 97.73 168.272 168.272 214.92 214.92 260.88 260.88 334.87 334.87 405.10 405.10 502.85 502.85 720.02 720.02 |
154 157 95.4 84.7 93.1 81.8 67.1 65.5 62.6 68.7 56.2 54.7 52.7 51.3 50.1 53.0 42.9 36.5 39.5 34.2 28.9 34.1 33.4 36.8 30.2 27.5 26.6 23.1 19.4 18.4 |
99 101 61 55 60 53 43 42 40 44 36 35 34 33 32 34 28 23 25 22 19 22 22 24 19 18 17 15 12 12 |
1.99 2.01 1.79 1.74 1.78 1.72 1.64 1.62 1.60 1.65 1.56 1.55 1.53 1.52 1.51 1.53 1.44 1.37 1.40 1.34 1.27 1.34 1.33 1.37 1.29 1.25 1.23 1.17 1.10 1.07 |
8.9 9.0 9.0 9.0 9.0 9.0 8.9 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 8.9 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
2 Due to a technical problem with the UPLC, samples taken and pretreated on 27 Feb 2017 had to be stored overnight at room temperature in the autosampler until analysis on 28 Feb 2017.
Main test – hydrolysis of the test item at pH 9 and 60 °C
Sampling time [hours] |
Analysed concentration1 [μg/L] |
Relative concentration [%] |
Logarithm relative concentration |
Actual pH |
0.00 0.00 21.63 21.63 43.30 43.30 117.70 117.70 285.55 285.55 381.73 381.73 456.25 456.25 624.50 624.50 720.17 720.17 |
163 160 77.4 96.1 75.7 75.2 75.8 75.1 82.2 78.3 62.3 58.8 68.7 57.2 50.6 49.4 53.5 61.1 |
101 99 48 59 47 47 47 46 51 48 39 36 43 35 31 31 33 38 |
2.00 2.00 1.68 1.77 1.67 1.67 1.67 1.67 1.71 1.69 1.59 1.56 1.63 1.55 1.50 1.49 1.52 1.58 |
8.9 8.9 8.9 8.9 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 9.0 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Recoveries at pH 9
Temperature (°C) |
Nominal concentration1 [μg/L] |
Analysed concentration [μg/L] |
Recovery [%] |
Mean recovery [%] |
20 |
200 200 |
138 140 |
69 70 |
69 |
50 |
200 200 |
154 157 |
77 79 |
78 |
60 |
200 200 |
163 160 |
82 80 |
81 |
1Based on the response of the peak recorded at the transition m/z 398.2 → m/z 134
Statistical parameters of the regression curves at pH 9
Temperature (°C) |
Slope [hours-1] |
Intercept |
Coefficient of correlation |
20
50
60
|
2.65 x 10-4
-6.86 x 10-4
-2.77 x 10-4 |
1.18
1.55
1.71 |
0.69
0.96
0.84 |
Rate constants (kobs) and half-life time (t½) at pH 9
Temperature [°C] |
kobs [hours-1] |
t½ [days] |
20
50
60
|
-6.11 x 10-4
1.58 x 10-3
6.37 x 10-4 |
-47
18
45 |
Description of key information
The half-life times of the test item were:
pH 4 |
pH 7 |
pH 9 |
|||
Temperature [°C] |
t½ [days] |
Temperature [°C] |
t½ [days] |
Temperature [°C] |
t½ [days] |
20 50 60 |
9249 20 18 |
20 50 60 |
-1687 18 33 |
20 50 60 |
-47 18 45 |
Key value for chemical safety assessment
- Half-life for hydrolysis:
- -1 687 d
- at the temperature of:
- 20 °C
Additional information
The rate of hydrolysis of the test item as a function of pH was determined at pH values normally found in the environment (pH 4-9).
The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of MLA-3202 at pH values normally found in the environment (pH 4-pH 9).
The results however are not as expected for hydrolysis. For hydrolysis, rate constants and slopes increase by a factor 2 to 3 with a 10 °C increase in temperature. This was not observed.
Even a negative half-life time was obtained at 20 °C at pH 7 and pH 9 due to a slight increase of concentration with time which is not possible in case of hydrolysis.
Based on the relatively low recovery at start of the tests and the steep decrease in concentration during the first hours of the tests at 50 and 60 °C, it is expected that the decrease in concentration observed in the various tests at pH 4, pH 7 and pH 9 is most probably due to adsorption and/or limited solubility in the buffer solutions and not due to hydrolysis. The amide bond in the various compounds present in MLA-3202 is expected to be stable at pH 4, pH 7 and pH 9.
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