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EC number: 601-779-5 | CAS number: 121451-02-3
- 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:
- 25 June 1999 to 03 November 1999
- 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)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA Guideline Subdivision N 161-1 (Hydrolysis)
- Deviations:
- no
- GLP compliance:
- yes
- Radiolabelling:
- yes
- Analytical monitoring:
- yes
- Details on sampling:
- - Sampling intervals for the parent/transformation products: Duplicate samples were taken at 0, 1, 3, 6, 13, 21 and 33 days after treatment for the 25 °C samples and on day 7 for the 50 °C samples; all aliquots were collected using a silanised glass syringe.
- Sampling intervals/times for pH measurements: 1-2 mL were sampled at 0, 1, 3, 6, 13, 21 and 33 days after treatment for the 25 °C samples and on day 7 for the 50 °C samples; all aliquots were collected using a silanised glass syringe.
- Sampling intervals/times for sterility check: Sterility checks were performed at study initiation and each sampling time: 0, 1, 3, 6, 13, 21 and 33 days after treatment for the 25 °C samples and on day 7 for the 50 °C samples; all aliquots were collected using a silanised glass syringe. 500 µL of the test solution or buffer was added to 10 mL of soy broth solution. The solutions were incubated for 3 days at 25 °C. Positive and negative controls were performed for each sterility check. - Buffers:
- - pH: 5, 7 and 9
- Composition of buffer: Buffers were prepared using water purified by a Millipore purification unit. The pH 5 buffer was prepared by adjusting 0.01 M sodium acetate trihydrate with glacial acetic acid. The pH 7 buffer was prepared by adjusting 0.01 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid with 2.0 N NaOH. The pH 9 buffer was prepared by adjusting 0.01 M sodium borate with concentrated HCl. All buffers were sterilised by autoclaving. - Details on test conditions:
- TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Silanised glass vials
- Sterilisation method: Autoclaving
- Is there any indication of the test material adsorbing to the walls of the test apparatus? Silanised glass vials were used to reduce sorption to the containers. The test vessels were selected based on preliminary suitability tests.
TEST MEDIUM
- Volume used/treatment 40 mL
- Kind and purity of water: Millipore purified water
- Preparation of test medium: 15 µL of a 5 ng/mL dosing solution containing the test material was added to 40 mL of buffer solution in individual silanised glass vials. The application rate was 2 ng/mL. - Duration:
- 33 d
- pH:
- 5
- Temp.:
- 25 °C
- Initial conc. measured:
- ca. 1.896 - 1.898 µg/L
- Duration:
- 33 d
- pH:
- 7
- Temp.:
- 25 °C
- Initial conc. measured:
- ca. 1.874 µg/L
- Duration:
- 33 d
- pH:
- 9
- Temp.:
- 25 °C
- Initial conc. measured:
- ca. 1.97 - 1.984 µg/L
- Number of replicates:
- 2
- Positive controls:
- no
- Remarks:
- Controls were only included for buffer sterility checks
- Negative controls:
- no
- Remarks:
- Controls were only included for buffer sterility checks
- Statistical methods:
- Statistical methods included calculation of means, standard deviations, r², and slope. Data were entered into a Microsoft Excel spreadsheet for all calculations, including linear regression analysis of degradation kinetics. Within an Excel spreadsheet, intermediate values were not rounded prior to final calculation.
Plotting a regression analysis of In Parent concentration versus time gave a slope, which is equal to - k'b (the observed decay rate constant (days^-1)). For the pH 9 samples this regression analysis gives a k’b value of 0.036 days^-1. This was used to calculate half-life and DT90 value using the following:
t1/2 = 0.693 / 0.036 days^-1
DT90 = ln (10 %) / 0.036 days^-1
The second-order rate constant was calculated at pH 9 using the following:
The concentration of OH- is 10E-05 M, therefore: kb = k’b / [OH-] = 0.036 days^-1 / 10E-05 M
The second-order rate constant was used to predict the pseudo first-order rate constant (k'b) at various pH values using the following:
k'b = k’b[OH-] - Transformation products:
- yes
- No.:
- #1
- No.:
- #2
- No.:
- #3
- No.:
- #4
- Details on hydrolysis and appearance of transformation product(s):
- - Pathways for transformation: At pH 5 and 7, the test material was found to be stable to hydrolysis (slightly positive slope). At pH 9, degradation was assumed to be due to base-catalysed hydrolysis.
- % Recovery:
- 93.7
- pH:
- 5
- Temp.:
- 50 °C
- Duration:
- 7 d
- % Recovery:
- 78.6
- pH:
- 7
- Temp.:
- 50 °C
- Duration:
- 7 d
- % Recovery:
- 8.5
- pH:
- 9
- Temp.:
- 50 °C
- Duration:
- 7 d
- % Recovery:
- 100
- pH:
- 5
- Temp.:
- 25 °C
- Duration:
- 33 d
- % Recovery:
- 94.8 - 96.2
- pH:
- 7
- Temp.:
- 25 °C
- Duration:
- 33 d
- % Recovery:
- 28.9 - 30.5
- pH:
- 9
- Temp.:
- 25 °C
- Duration:
- 33 d
- pH:
- 5
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- -0.002 d-1
- Remarks on result:
- other: r² = 0.590. Half-life was not calculated due to no degradation being observed
- Key result
- pH:
- 7
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- -0.001 d-1
- Remarks on result:
- other: r² = 0.095. Half-life was not calculated due to no degradation being observed
- pH:
- 9
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.036 d-1
- DT50:
- 19 d
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: r² = 0.989, DT90 = 64
- pH:
- 11
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 3.6 d-1
- DT50:
- 0.19 d
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: Calculated using a second-order rate constant of 3600 days^-1 M^-1
- pH:
- 7
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0 d-1
- DT50:
- 1 930 d
- Type:
- second order
- Remarks on result:
- other: Calculated using a second-order rate constant of 3600 days^-1 M^-1
- Details on results:
- TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
PATHWAYS OF HYDROLYSIS
- Description of pathways: Degradation at pH 9 was assumed to be due to base-catalysed hydrolysis. As hydroxide ions were in large excess, it was assumed to be a constant; this forced the degradation into first order form. The degradation of the test material was therefore through pseudo-first-order. From the values calculated for pH 9 at 25 °C, a second-order rate constant was derived which could be used to calculate the half-lives at different pH values.
- Figures of chemical structures attached: Yes - Validity criteria fulfilled:
- yes
- Remarks:
- Recovery of the test material was acceptable; where recovery was too low at individual endpoints, these were excluded from analyses.
- Conclusions:
- Under the conditions of the test, the test material was stable to hydrolysis at pH 5 and 7. At pH 9, the test material degraded through base-catalysed hydrolysis following pseudo-first-order kinetics to form four metabolites (urea, amine, amide and difluorobenzoic acid forms of the parent material). At pH 9, the half-life was 19 days with a DT90 of 64 days.
- Executive summary:
The hydrolysis of the test material was investigated in a study conducted in accordance with the standardised guidelines OECD 111, EU Method C.7 and US EPA 161-1 under GLP conditions.
The rate and route of hydrolysis was studied at pH 5, 7, and 9 using [14C]radiolabelled material. The pseudo first-order rate constant was determined and used to calculate the half-life and DT90 of hydrolysis at pH 9. The second-order rate constant at pH 9 was calculated and used to predict degradation rates at various pH values, and degradates approaching or exceeding 10 % of applied radiocarbon were identified.
Samples (2 ng/mL) were incubated at 25 ± 1 °C and sampling times were 0, 1,3,6, 13,21, and 33 days after treatment. Additional samples were incubated at 50 °C and collected at 1 day after treatment (pH 9 only) and 7 days after treatment (pH 5, 7, and 9). All samples were analysed by reverse phase HPLC.
The samples were sterile throughout the study and the pH for all samples was constant. Average material balance for kinetics samples ranged from 101.5 % at pH 9 to 103.3 % at pH 7.
The test material was degraded via base-catalysed hydrolysis. Following 7 days of incubation at 50 °C, it was stable to hydrolysis at pH 5 (93.7 % remaining), slightly hydrolysed at pH 7 (78.6 % remaining) and mostly hydrolysed at pH 9 (8.5 % remaining). At 25°C the test material was stable to hydrolysis at pH 5 and 7. Therefore, rate constants and observed half-life values were not calculated at these pH values. At pH 9, the pseudo-first order rate constant of the test material hydrolysis was 0.036 days^-1 giving half-life and DT90 values of 19 days and 64 days, respectively. The second-order rate constant of hydrolysis was 3600 days^-1 M^-1, giving predicted half-life values of 0.19 days at pH 11 to 1930 days at pH 7. At pH 9, the test material was hydrolysed to form urea, amine, amide, and difluorobenzoic acid forms of the parent material. The study met all required validity criteria.
Reference
Table 1: Hydrolysis of the test material after 7 days at 50 °C
pH |
Replicate |
Percent of Applied |
|||
Parent |
Urea metabolite |
Amine metabolite |
|||
Actual |
Average |
||||
5 |
A |
91.8 |
93.7 |
1.2 |
3.4 |
B |
95.6 |
0.9 |
1.3 |
||
7 |
A |
77.6 |
78.6 |
15.1 |
5.6 |
B |
79.6 |
12.9 |
6.2 |
||
9 |
A |
8.9 |
8.5 |
42.7 |
18.4 |
B |
8.1 |
59.7 |
23.2 |
Table 2: Hydrolysis of the test material at 25 °C
Sample Time (days) |
Replicate |
Percent of Applied |
||||
Parent |
Urea metabolite at pH 9 |
Amine metabolite at pH 9 |
||||
pH 5 |
pH 7 |
pH 9 |
||||
0 |
A |
94.9 |
- |
98.5 |
0.7 |
0.0 |
B |
94.8 |
93.7 |
99.2 |
0.0 |
0.0 |
|
1 |
A |
- |
92.9 |
89.9 |
3.0 |
1.9 |
B |
95.0 |
99.3 |
87.3 |
3.6 |
1.5 |
|
3 |
A |
96.1 |
97.2 |
84.9 |
8.2 |
3.6 |
B |
91.2 |
85.8 |
82.5 |
4.5 |
4.1 |
|
6 |
A |
94.9 |
- |
77.2 |
17.1 |
2.7 |
B |
91.6 |
92.3 |
75.3 |
18.1 |
3.1 |
|
13 |
A |
99.4 |
100 |
- |
- |
- |
B |
96.5 |
97.2 |
- |
- |
- |
|
21 |
A |
98.0 |
98.5 |
45.3 |
35.5 |
13.6 |
B |
96.8 |
99.1 |
39.4 |
37.5 |
10.0 |
|
33 |
A |
100 |
96.2 |
28.9 |
40.9 |
8.3 |
B |
100 |
94.8 |
30.5 |
50.7 |
9.1 |
- Not calculated due to low recovery
Description of key information
Hydrolysis = pH 9, 19 days at 25 °C, OECD 111, EU Method C.7, US EPA 161-1, Cook (1999)
Key value for chemical safety assessment
- Half-life for hydrolysis:
- 19 d
- at the temperature of:
- 25 °C
Additional information
In the key study (Cook 1999), the hydrolysis of the test material was investigated in a study conducted in accordance with the standardised guidelines OECD 111, EU Method C.7 and US EPA 161-1 under GLP conditions. The study was assigned a reliability score of 1 in accordance with the principles for assessing data quality as defined in Klimisch et al. (1997).
The rate and route of hydrolysis was studied at pH 5, 7, and 9 using [14C]radiolabelled material. The pseudo first-order rate constant was determined and used to calculate the half-life and DT90 of hydrolysis at pH 9. The second-order rate constant at pH 9 was calculated and used to predict degradation rates at various pH values, and degradates approaching or exceeding 10 % of applied radiocarbon were identified.
Samples (2 ng/mL) were incubated at 25 ± 1 °C and sampling times were 0, 1,3,6, 13,21, and 33 days after treatment. Additional samples were incubated at 50 °C and collected at 1 day after treatment (pH 9 only) and 7 days after treatment (pH 5, 7, and 9). All samples were analysed by reverse phase HPLC.
The samples were sterile throughout the study and the pH for all samples was constant. Average material balance for kinetics samples ranged from 101.5 % at pH 9 to 103.3 % at pH 7.
The test material was degraded via base-catalysed hydrolysis. Following 7 days of incubation at 50 °C, it was stable to hydrolysis at pH 5 (93.7 % remaining), slightly hydrolysed at pH 7 (78.6 % remaining) and mostly hydrolysed at pH 9 (8.5 % remaining). At 25°C the test material was stable to hydrolysis at pH 5 and 7. Therefore, rate constants and observed half-life values were not calculated at these pH values. At pH 9, the pseudo-first order rate constant of the test material hydrolysis was 0.036 days^-1 giving half-life and DT90 values of 19 days and 64 days, respectively. The second-order rate constant of hydrolysis was 3600 days^-1 M^-1, giving predicted half-life values of 0.19 days at pH 11 to 1930 days at pH 7. At pH 9, the test material was hydrolysed to form urea, amine, amide, and difluorobenzoic acid forms of the parent material. The study met all required validity criteria.
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