Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 262-811-8 | CAS number: 61477-96-1
- 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:
- 16/05/2018 – 13/09/2018
- 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
- GLP compliance:
- yes (incl. QA statement)
- Radiolabelling:
- no
- Analytical monitoring:
- yes
- Details on sampling:
- - Sampling method: Individual replicate test samples (a minimum of duplicate samples contained in separate reaction vessels) were removed from the incubator and the contents analysed at each of at least 6 sampling times.
- Sampling intervals/times for measurements:
- Tier I samples were measured at day 0 and after 5 days;
- Tier II: The test was conducted until 90% hydrolysis was observed: At pH 4 (20ºC), the amount of parent compound was measured at 0, 4, 25, 73, 145, 168, and 192 h after the start of the test; at pH 4 (30ºC), it was measured at 0, 1, 18, 25, 43, 91, 163, 187 and 214 h; at pH 4 (50ºC), it was measured at 0, 4, 5, 22, 26, 27, and 47 h. At pH 7 (20ºC), it was measured at 0, 3, 21, 48, 96 and 168 h; at pH 7 (30ºC), at 0, 17, 24, 42, 90, 162, 714 h; at pH 7 (50ºC), at 0, 4, 5, 22, 27, 28 and 143 h. At pH 9 (20ºC), it was measured at 0, 3, 21, 28, 46, and 50 h; at pH 9 (30ºC), at 0, 18, 21, 22 h; and at pH 9 (50ºC), at 0, 1, 3, and 4 h after the start of the test.
- Tier III: sampling was performed after 24 hours of hydrolysis at 50 ºC, in all the pH tested (4, 7, 9). - Buffers:
- - pH: 4.0, 7.0, 9.0 (commercial buffers, no further details).
- Details on test conditions:
- TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: glass flasks fitted with glass stoppers, incubator, magnetic stirrer, pH-meter.
- Measures taken to avoid photolytic effects: preliminary tests were performed in the dark incubator.
- If no traps were used, is the test system: closed.
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no.
TEST MEDIUM
- Volume used/treatment
- Kind and purity of water: water for HPLC (Milipore)
- Preparation of test medium: BUFFER
- Renewal of test solution: no.
- Identity and concentration of co-solvent:
OTHER TEST CONDITIONS
- Adjustment of pH: no.
- Dissolved oxygen: - Number of replicates:
- 2
- Positive controls:
- no
- Negative controls:
- no
- Statistical methods:
- The statistical calculations and the graphs were performed using SigmaPlot 9.0 software of SYSTAT Software, Inc., USA purchased from GAMBIT CoiS Ltd, Poland.
- Preliminary study:
- - Measurements in buffer solution at pH 4.0: The determined rate constant after 5 days at 50ºC was 0.048 h-1 and the half-life period was 14.5h (>12h). About 96.5% of the test item had been hydrolyzed after 5 days.
- Measurements in buffer solution at pH 7.0: The determined rate constant after 5 days at 50ºC was 0.033 h-1 and the half-life period was 21.2h (>12h). About 96.7% of the test item had been hydrolyzed after 5 day.
- Measurements in buffer solution at pH 9.0: The determined rate constant after 5 days at 50ºC was 0.544 h-1 and the half-life period was 1.27h (<12h), so it was deemed hydrolytically unstable. About 93.1% of the test item had been hydrolyzed after 5 days.
- On the basis of these results, Tier 2 and 3 studies were performed. - Test performance:
- No abnormal observations or deviations reported.
- Transformation products:
- yes
- No.:
- #1
- No.:
- #2
- No.:
- #3
- No.:
- #4
- Key result
- pH:
- 4
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0.009 h-1
- DT50:
- 80.24 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 4
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.01 h-1
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: calculated
- Key result
- pH:
- 4
- Temp.:
- 30 °C
- Hydrolysis rate constant:
- 0.01 h-1
- DT50:
- 64.77 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 4
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.048 h-1
- DT50:
- 14.5 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 7
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0.004 h-1
- DT50:
- 175 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 7
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.005 h-1
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: calculated
- Key result
- pH:
- 7
- Temp.:
- 30 °C
- Hydrolysis rate constant:
- 0.005 h-1
- DT50:
- 149 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 7
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.033 h-1
- DT50:
- 21.19 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 9
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0.043 h-1
- DT50:
- 16.15 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 9
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.066 h-1
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: calculated
- Key result
- pH:
- 9
- Temp.:
- 30 °C
- Hydrolysis rate constant:
- 0.097 h-1
- DT50:
- 7.14 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Key result
- pH:
- 9
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.544 h-1
- DT50:
- 1.27 h
- Type:
- (pseudo-)first order (= half-life)
- Remarks on result:
- other: experimental
- Other kinetic parameters:
- Activation energy, E = 46.859 kJ/mol (pH 4), 58.329 kJ/mol (pH 7), 67.107 kJ/mol (pH 9).
- Details on results:
- TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes, pH and temperature were set and maintaned at various fixed values.
- Anomalies or problems encountered: no.
MAJOR TRANSFORMATION PRODUCTS
At pH4:
- Transformation products observed were 2-(2-{2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-vinylamino)-3,3-dimethyl-butyric acid; (5,5-Dimethyl-thiazolidin-2-yl)-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-acetic acid; and 2-({2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid.
At pH7:
- Transformation products observed were 2-(2-{2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-vinylamino)-3,3-dimethyl-butyric acid; (5,5-Dimethyl-thiazolidin-2-yl)-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-acetic acid; and 2-({2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid.
At pH9:
- The transformation product observed was: 2-(Carboxy-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid.
INDICATION OF UNSTABLE TRANSFORMATION PRODUCTS: no.
PATHWAYS OF HYDROLYSIS
- Figures of chemical structures attached: Yes - Validity criteria fulfilled:
- yes
- Conclusions:
- The substance was found to be hydrolitically unstable only at pH 9 (≥ 30ºC) with a half-life < 12h. The major hydrolysis products were identified as 2-(2-{2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-vinylamino)-3,3-dimethyl-butyric acid, 5,5-Dimethyl-thiazolidin-2-yl-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-acetic acid and 2-({2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 4 and pH 7; and as 2-(Carboxy-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 9.
- Executive summary:
An hydrolysis study was conducted on the test item, according to OECD TG 111 / EU C.7 (Hydrolysis as a function of pH), under GLP conditions. A validated HPLC method was used for determining the content of the test substance in the samples. A preliminary Tier 1 test was conducted at pH 4.0, 7.0 and 9.0 and 50ºC, which showed that the test item is hydrolitically unstable at pH 9, and >90% of the substance was degraded after 5 days, so further testing was necessary. Based on this data, Tier 2 assays were performed at 20, 30 and 50ºC and at three pH values (4.0, 7.0 and 9.0) in order to determe the hydrolysis rate constants and half-life periods for the test item. Finally, a Tier 3 assay was conducted to identify the major hydrolysis products by UPLC-MS. The results obtained are as follows:
Temperature, ºC
pH
4
7
9
20 ºC (exp)
kobs= 0.00864 h-1
t0.5= 80.24 h
kobs= 0.00396 h-1
t0.5= 175.0 h
kobs= 0.0429 h-1
t0.5= 16.15 h
25 ºC (calculated)
kcalc= 0.0101 h-1
kcalc= 0.00460 h-1
kcalc= 0.0657
30 ºC (exp)
kobs= 0.0107 h-1
t0.5= 64.77 h
kobs= 0.00465h-1
t0.5= 149.0 h
kobs= 0.0971 h-1
t0.5= 7.14 h
50 ºC (exp)
kobs= 0.0478 h-1
t0.5= 14.50 h
kobs= 0. 0327 h-1
t0.5= 21.19 h
kobs= 0.544 h-1
t0.5= 1.27 h
The substance was found to be hydrolitically unstable only at pH 9 (≥ 30ºC) with a half-life < 12h. The major hydrolysis products were identified as #1: 2-(2-{2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-vinylamino)-3,3-dimethyl-butyric acid, #2: 5,5-Dimethyl-thiazolidin-2-yl-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-acetic acid, #3: 2-({2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 4 and pH 7; and as #4: 2-(Carboxy-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 9. Based on the quantification results, the main hydrolysis product is #4 (40-60%).
Reference
Table 1. Preliminary study results.
pH |
4.0 |
7.0 |
9.0 |
||||
Time (d) at 50ºC |
0 |
5 |
0 |
5 |
0 |
5 |
|
Concentration (mg/L) |
R1 |
668.7 |
23.5 |
2487.4 |
83.4 |
5289.5 |
372.0 |
R2 |
679.7 |
23.2 |
2519.1 |
82.2 |
5678.5 |
381.0 |
|
Average conc. (mg/L) |
674.2 |
23.4 |
2503.3 |
82.8 |
5484.0 |
376.5 |
|
Concentration loss (%) |
96.5 |
96.7 |
93.1 |
||||
pH, measured |
4.00 |
4.02 |
6.98 |
6.97 |
8.65 |
8.67 |
Table 2. Full hydrolysis study, summary of results: Hydrolysis rate, half-life period and activation energy.
temperature, ºC |
pH |
4 |
7 |
9 |
20 ºC (exp) |
kobs= 0.00864 h-1 t0.5= 80.24 h |
kobs= 0.00396 h-1 t0.5= 175.0 h |
kobs= 0.0429 h-1 t0.5= 16.15 h |
|
25 ºC (calculated) |
kcalc= 0.0101 h-1 |
kcalc= 0.00460 h-1 |
kcalc= 0.0657 |
|
30 ºC (exp) |
kobs= 0.0107 h-1 t0.5= 64.77 h |
kobs= 0.00465h-1 t0.5= 149.0 h |
kobs= 0.0971 h-1 t0.5= 7.14 h |
|
50 ºC (exp) |
kobs= 0.0478 h-1 t0.5= 14.50 h |
kobs= 0. 0327 h-1 t0.5= 21.19 h |
kobs= 0.544 h-1 t0.5= 1.27 h |
|
Activation energy E, kJ/mol |
46.859 |
58.329 |
67.107 |
Table 3. Quantification of transformation products.
pH |
Temp. ºC |
Initial conc. of PA, mg/L |
Final conc. of PA, mg/L |
Final time, hours |
Percentage of the detected substances, % |
|||||
PA |
#1 |
#2 |
#3 |
#4 |
#5 |
|||||
4 |
20 |
506.7 |
50.4 |
192 |
17.36 |
2.34 |
0.79 |
9.22 |
64.07 |
5.53 |
4 |
30 |
476.3 |
46.5 |
214 |
16.25 |
3.23 |
1.50 |
2.67 |
69.90 |
6.45 |
4 |
50 |
506.8 |
50.5 |
47 |
15.22 |
1.09 |
2.03 |
0.40 |
73.82 |
7.44 |
7 |
20 |
523.0 |
15.6 |
694 |
10.54 |
2.00 |
9.32 |
1.84 |
68.42 |
7.89 |
7 |
30 |
496.6 |
19.1 |
714 |
13.18 |
0.33 |
1.19 |
3.98 |
67.98 |
13.33 |
7 |
50 |
490.5 |
4.5 |
143 |
14.90 |
2.43 |
1.20 |
4.03 |
61.75 |
15.68 |
9 |
20 |
453.5 |
51.9 |
50 |
9.64 |
0.37 |
22.39 |
17.70 |
49.81 |
0.09 |
9 |
30 |
463.6 |
26.4 |
22 |
10.22 |
0.77 |
26.23 |
18.35 |
39.86 |
4.56 |
9 |
50 |
402.6 |
47.7 |
4 |
7.14 |
1.50 |
27.10 |
16.70 |
43.37 |
3.98 |
Description of key information
Key study. Method according to OECD 111, GLP Study. The substance is hydrolytically unstable at pH 9 (30 and 50ºC), with a half-life <12h. The major hydrolysis products were identified as #1: 2-(2-{2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-vinylamino)-3,3-dimethyl-butyric acid, #2: 5,5-Dimethyl-thiazolidin-2-yl)-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-acetic acid, #3: 2-({2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 4 and pH 7; and #4 (main): 2-(Carboxy-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 9.
Key value for chemical safety assessment
- Half-life for hydrolysis:
- 1 h
- at the temperature of:
- 25 °C
Additional information
An hydrolysis study was conducted on the test item, according to OECD TG 111 / EU C.7 (Hydrolysis as a function of pH), under GLP conditions. A validated HPLC method was used for determining the content of the test substance in the samples. A preliminary Tier 1 test was conducted at pH 4.0, 7.0 and 9.0 and 50ºC, which showed that the test item is hydrolitically unstable at pH 9, and >90% of the substance was degraded after 5 days, so further testing was necessary. Based on this data, Tier 2 assays were performed at 20, 30 and 50ºC and at three pH values (4.0, 7.0 and 9.0) in order to determe the hydrolysis rate constants and half-life periods for the test item. Finally, a Tier 3 assay was conducted to identify the major hydrolysis products by UPLC-MS. The results obtained are as follows:
Temperature, ºC |
pH |
4 |
7 |
9 |
20 ºC (exp) |
kobs= 0.00864 h-1 t0.5= 80.24 h |
kobs= 0.00396 h-1 t0.5= 175.0 h |
kobs= 0.0429 h-1 t0.5= 16.15 h |
|
25 ºC (calculated) |
kcalc= 0.0101 h-1 |
kcalc= 0.00460 h-1 |
kcalc= 0.0657 |
|
30 ºC (exp) |
kobs= 0.0107 h-1 t0.5= 64.77 h |
kobs= 0.00465h-1 t0.5= 149.0 h |
kobs= 0.0971 h-1 t0.5= 7.14 h |
|
50 ºC (exp) |
kobs= 0.0478 h-1 t0.5= 14.50 h |
kobs= 0. 0327 h-1 t0.5= 21.19 h |
kobs= 0.544 h-1 t0.5= 1.27 h |
The substance was found to be hydrolitically unstable only at pH 9 (≥ 30ºC) with a half-life < 12h. The major hydrolysis products were identified as 2-(2-{2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-vinylamino)-3,3-dimethyl-butyric acid, 5,5-Dimethyl-thiazolidin-2-yl)-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-acetic acid and 2-({2-[(4-Ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 4 and pH 7; and as 2-(Carboxy-{2-[(4-ethyl-2,3-dioxo-piperazine-1-carbonyl)-amino]-2-phenyl-acetylamino}-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid at pH 9. Based on the quantification results, the main hydrolysis product is #4 (40-60%).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.