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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 257-913-4 | CAS number: 52434-90-9
- 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:
- 12 September 2022 to 14 November 2023
- 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)
- GLP compliance:
- yes (incl. QA statement)
- Radiolabelling:
- no
- Analytical monitoring:
- yes
- Details on sampling:
- - Sampling intervals for the parent/transformation products: Two samples of each pH buffer and one control of each pH buffer were taken immediately after the addition of the test item on day 0 analysis, and on day 3 and day 5 of incubation at 50 ± 0.5ºC during preliminary test.
During Tier 2 test, all the test samples and blank control were analyzed for active content concentration as detailed in the full study report (paragraph 7.6.4) after incubation at 20°C, 35°C, and 50°C.
- Sampling intervals/times for pH measurements: The pH was measured after fortification of the test item stock and at the time of each sampling occasion for each buffer solution and control using a pH meter both for preliminary and Tier 2 tests.
- Sampling intervals/times for sterility check: Sterility was checked at higher kinetic test tier 2 experimental start 0th Hour (before incubation) in all the test systems and at experiment termination as follows: 20th Hour in pH 4, pH 7 and pH 9 buffer solutions incubated at 50°C, at 24th Hour in pH 4, pH 7 and pH 9 buffers at 35°C, at 24th Hour in pH 4 buffer at 20°C and at 96th Hour in pH 7 and pH 9 buffers at 20 °C respectively. The test solutions were prepared aseptically under a biosafety cabinet chamber. A volume of 5 mL of each sample was collected and transferred to the microbiology department for sterility testing. - Buffers:
- Buffer solutions at pH 4, 7 and 9 were prepared according to the buffer systems of Clark and Lubs.
- Details on test conditions:
- TEST SYSTEM
- Sterilisation method: All glassware, Milli-Q water and buffer solutions of pH 4, pH 7 and pH 9 (test system) used in the hydrolysis tests were sterilized using autoclave at 121.0°C for 15 minutes at 15 lbs pressure.
- Lighting: All the hydrolysis tests were carried out in dark conditions.
- Measures taken to avoid photolytic effects: The test tubes were covered with aluminium foil to avoid photolytic effects.
- Measures to exclude oxygen: All necessary measures were taken to avoid the presence of oxygen by bubbling nitrogen for 5 minutes before preparing the solution. - Duration:
- 5 d
- pH:
- 4
- Temp.:
- 50 °C
- Initial conc. measured:
- 18.785 mg/L
- Remarks:
- Tier 1 test.
Mean measured concentration. - Duration:
- 5 d
- pH:
- 7
- Temp.:
- 50 °C
- Initial conc. measured:
- 18.949 mg/L
- Remarks:
- Tier 1 test.
Mean measured concentration. - Duration:
- 5 d
- pH:
- 9
- Temp.:
- 50 °C
- Initial conc. measured:
- 19.091 mg/L
- Remarks:
- Tier 1 test.
Mean measured concentration. - Duration:
- 20 h
- pH:
- 4
- Temp.:
- 50 °C
- Initial conc. measured:
- 18.593 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 20 h
- pH:
- 7
- Temp.:
- 50 °C
- Initial conc. measured:
- 18.8 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 20 h
- pH:
- 9
- Temp.:
- 50 °C
- Initial conc. measured:
- 18.901 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 24 h
- pH:
- 4
- Temp.:
- 35 °C
- Initial conc. measured:
- 18.593 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 24 h
- pH:
- 7
- Temp.:
- 35 °C
- Initial conc. measured:
- 18.758 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 24 h
- pH:
- 9
- Temp.:
- 35 °C
- Initial conc. measured:
- 18.901 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 24 h
- pH:
- 4
- Temp.:
- 20 °C
- Initial conc. measured:
- 18.593 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 96 h
- pH:
- 7
- Temp.:
- 20 °C
- Initial conc. measured:
- 18.758 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Duration:
- 96 h
- pH:
- 9
- Temp.:
- 20 °C
- Initial conc. measured:
- 18.901 mg/L
- Remarks:
- Tier 2 test.
Mean measured concentration. - Number of replicates:
- 2 replicates for each buffer, at each of the temperatures tested
- Positive controls:
- no
- Negative controls:
- yes
- Remarks:
- 1 control for each buffer, at each of the temperatures tested
- Statistical methods:
- Standard calculations according to OECD 111 and pseudo first-order equations
- Preliminary study:
- The preliminary test results revealed that the rate of hydrolysis (percent degradation) of the test item after 5 days of incubation at 50 ± 0.2°C was 93.47% in pH 4 buffer, 91.95% in pH 7 buffer and 93.50% in pH 9 buffer solutions respectively.
- Transformation products:
- no
- pH:
- 9
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.071 h-1
- DT50:
- 9.69 h
- pH:
- 7
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.057 h-1
- DT50:
- 12.12 h
- pH:
- 4
- Temp.:
- 25 °C
- Hydrolysis rate constant:
- 0.112 h-1
- DT50:
- 6.17 h
- pH:
- 9
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.167 h-1
- DT50:
- 4.15 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 9
- Temp.:
- 35 °C
- Hydrolysis rate constant:
- 0.114 h-1
- DT50:
- 6.06 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 9
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0.056 h-1
- DT50:
- 12.36 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 7
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.154 h-1
- DT50:
- 4.49 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 7
- Temp.:
- 35 °C
- Hydrolysis rate constant:
- 0.089 h-1
- DT50:
- 7.81 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 7
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0.045 h-1
- DT50:
- 15.24 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 4
- Temp.:
- 50 °C
- Hydrolysis rate constant:
- 0.182 h-1
- DT50:
- 3.82 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 4
- Temp.:
- 35 °C
- Hydrolysis rate constant:
- 0.127 h-1
- DT50:
- 5.45 h
- Type:
- (pseudo-)first order (= half-life)
- pH:
- 4
- Temp.:
- 20 °C
- Hydrolysis rate constant:
- 0.105 h-1
- DT50:
- 6.61 h
- Type:
- (pseudo-)first order (= half-life)
- Details on results:
- TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes - Validity criteria fulfilled:
- yes
- Conclusions:
- The preliminary test was conducted at 50 ± 0.2°C, and after 5 days the test item AP 729 was found to be hydrolytically unstable due to 93.47% degradation in pH 4 buffer, 91.95% degradation in pH 7 buffer and 93.50% degradation in pH 9 buffer test solutions and no formation of breakdown products was observed respectively.
In Tier 2 test, the hydrolysis of the test item was investigated as a function of pH (4, 7 and 9) at three temperatures of 20 ± 0.5°C, 35 ± 0.5°C and 50 ± 0.5°C respectively.
At pH 4, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.1123 hour-1 and 6.17 hours, respectively.
At pH 7, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.0572 hour-1 and 12.12 hours, respectively.
At pH 9, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.0715 hour-1 and 9.69 hours, respectively.
At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.2409 hour-1 and 2.88 hours, respectively. - Executive summary:
The hydrolysis of AP 729 as a function of pH in Sterile Aqueous Buffer Solutions of pH 4, pH 7 and pH 9 was studied according to OECD Guideline 111. The hydrolysis of the test item was determined by analyzing the analyte concentration at the predetermined intervals using a validated HPLC method.
The analysis of duplicate buffer solutions after the addition of the test item indicated that mean recoveries of the test item in pH 4, pH 7 and pH 9 buffer solutions at initial analysis for tier 1 were 91.12%, 91.91% and 92.60% and for tier 2 were 90.35%, 91.14% and 91.84% and thus fell within the quality criteria of 90-110% for hydrolysis experiment. The recovery analysis demonstrated that the analytical method was adequate to support the hydrolysis study of the test item, providing an indication of the repeatability of the analytical method and of the uniformity of the application procedure for the test item in the Tier 1 test.The analytical method was sufficiently sensitive to quantify the test item concentrations down to 10% less than the initial concentration in the Tier tests.
A Preliminary test (Tier 1) was performed: the rate of hydrolysis at 50 ± 0.2°C was assessed for the test item at nominal fortified concentration of 20.6166 mg/L in pH 4, pH 7 and pH 9 buffers solutions.
The preliminary test results revealed that the rate of hydrolysis (percent degradation) of the test item after 5 days of incubation at 50 ± 0.2°C was 93.47% in pH 4 buffer, 91.95% in pH 7 buffer and 93.50% in pH 9 buffer solutions respectively. Based on the Tier 1 test results, the test item was considered as hydrolytically unstable as more than 10% hydrolysis was obtained and no formation of breakdown products was observed in pH 4, pH 7 and pH 9 buffers at 50 ± 0.2°C after 5 days.
Hence, further testing of Tier 2 was conducted for the test item in pH 4, pH 7 and pH 9 at nominal fortified concentration of 20.5810 mg/L with solutions being maintained at three different temperatures of 20.0 ± 0.5°C, 35.0 ± 0.5°C and 50.0 ± 0.5°C at various time periods.
The mean logarithms of the relative concentrations were plotted against time using linear regression analysis and the rate constant and half-life (DT50) were calculated from the Tier 2 results. Using the experimentally determined kobs for each pH and temperature, the temperature dependency was calculated using the relation ln K vs 1/T.With the regression parameters, by use of the Arrhenius relationships for acid, neutral and base catalysed hydrolysis, pseudo first-order rate constants Kobs (total), and thus half-lives were calculated for hydrolytically behavior of the test item at 25°C. Kobs (total) was calculated as sum of the experimentally determined rate constant values.
At pH 4, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.1123 hour-1 and 6.17 hours, respectively.
At pH 7, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.0572 hour-1 and 12.12 hours, respectively.
At pH 9, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.0715 hour-1 and 9.69 hours, respectively.
At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.2409 hour-1 and 2.88 hours, respectively.The pH of each of the test solutions was determined at all the intervals. The results show that there were no significant changes in the pH values in all the test solutions of respective buffers. The results show that the hydrolytic degradation of the test item under sterile conditions strongly depends on the temperature and the pH value. Based on Tier 2 test chromatograms, no breakdown products were detected, hence Tier 3 test for the identification of other products was not performed.
Sterility was checked at higher kinetic test tier 2 experimental start 0th Hour (before incubation) in all the test systems and at experiment termination as follows: 20th Hour in pH 4, pH 7 and pH 9 buffer solutions incubated at 50°C, at 24th Hour in pH 4, pH 7 and pH 9 buffers at 35°C, at 24th Hour in pH 4 buffer at 20°C and at 96th Hour in pH 7 and pH 9 buffers at 20 °C respectively.
During the sterility check, no microbial growth (bacteria) was observed in pH 4, pH 7 and pH 9 samples, respectively at the start and termination of the study.
Reference
Description of key information
The hydrolysis of AP 729 as a function of pH in Sterile Aqueous Buffer Solutions of pH 4, pH 7 and pH 9 was studied according to OECD Guideline 111 and was determined by analyzing the analyte concentration at the predetermined intervals using a validated HPLC method.
A Preliminary test (Tier 1) was performed: the rate of hydrolysis at 50 ± 0.2°C was assessed for the test item at nominal fortified concentration of 20.6166 mg/L in pH 4, pH 7 and pH 9 buffers solutions.
The preliminary test results revealed that the rate of hydrolysis (percent degradation) of the test item after 5 days of incubation at 50 ± 0.2°C was 93.47% in pH 4 buffer, 91.95% in pH 7 buffer and 93.50% in pH 9 buffer solutions respectively. Based on the Tier 1 test results, the test item was considered as hydrolytically unstable as more than 10% hydrolysis was obtained and no formation of breakdown products was observed in pH 4, pH 7 and pH 9 buffers at 50 ± 0.2°C after 5 days.
In Tier 2 test, the hydrolysis of the test item was investigated as a function of pH (4, 7 and 9) at three temperatures of 20 ± 0.5°C, 35 ± 0.5°C and 50 ± 0.5°C. The mean logarithms of the relative concentrations were plotted against time using linear regression analysis and the rate constant and half-life (DT50) were calculated from the Tier 2 results. Using the experimentally determined kobs for each pH and temperature, the temperature dependency was calculated using the relation ln K vs 1/T. With the regression parameters, by use of the Arrhenius relationships for acid, neutral and base catalysed hydrolysis, pseudo first-order rate constants Kobs (total), and thus half-lives were calculated for hydrolytically behavior of the test item at 25°C. Kobs (total) was calculated as sum of the experimentally determined rate constant values.
At pH 4, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.1123 hour-1 and 6.17 hours, respectively.
At pH 7, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.0572 hour-1 and 12.12 hours, respectively.
At pH 9, the rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.0715 hour-1 and 9.69 hours, respectively.
At pH 4, 7 and 9, the total rate constant and half-life of the reactions at 25ºC were calculated and found to be 0.2409 hour-1 and 2.88 hours, respectively.
Key value for chemical safety assessment
- Half-life for hydrolysis:
- 2.88 h
- at the temperature of:
- 25 °C
Additional information
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.