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EC number: 226-970-7 | CAS number: 5580-57-4
- 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
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Specific investigations: other studies
Administrative data
- Endpoint:
- specific investigations: other studies
- Remarks:
- Biodurability and biodissolution in phagolysosomal simulant fluid
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: ISO:TR19057:2017
- Version / remarks:
- Nti 2017, Nanotechnologies - Use and application of acellular in vitro tests and methodologies to assess nanomaterial biodurability
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD draft TG on “solubility in aqueous media”
- Version / remarks:
- restricted to the „screening method“
- Principles of method if other than guideline:
- The solubility of the test item was determined by a static and a dynamic dissolution test after pre-treatment steps for purification of the samples.
Because the test item is handled as powder, the human exposure to dust is considered the most critical scenario, so that dissolution needed to be tested in fluids that are relevant for inhalation. pH 4.5 phagolysosomal simulant fluid (PSF) was selected as recommended by ISO:TR19057:2017 (Nti, 2017, Nanotechnologies. Use and application of acellular in vitro tests and methodologies to assess nanomaterial biodurability).
For the static solubility experiment, the test material was suspended in a pH 4.5 phagolysosomal simulant fluid in a Schott glass bottle and dispersed by continuous ultrasonication during 5 h, followed by shaking to ensure homogeneity for a total incubation of 24 h. After filtration, the dissolved fractions were detected by UV-Vis.
For the dynamic dissolution kinetic experiment, a continuous flow-through system was applied with the test material captured in a flow cell method to determine the biodissolution of materials in relevant lung fluids. The flow cell mimics the non-equilibrium physiological conditions, where ions can be transported away from the lungs. The tempered medium was regulated at a constant flowrate by a pump at 37°C for 7 days and the fluid collection was performed with an autosampler. The particle size was analyzed by UV-Vis. - GLP compliance:
- no
- Type of method:
- other: in chemico
- Endpoint addressed:
- basic toxicokinetics
- repeated dose toxicity: inhalation
Test material
- Reference substance name:
- 3,3'-[(2-chloro-5-methyl-p-phenylene)bis[imino(1-acetyl-2-oxoethylene)azo]]bis[4-chloro-N-(3-chloro-o-tolyl)benzamide]
- EC Number:
- 226-970-7
- EC Name:
- 3,3'-[(2-chloro-5-methyl-p-phenylene)bis[imino(1-acetyl-2-oxoethylene)azo]]bis[4-chloro-N-(3-chloro-o-tolyl)benzamide]
- Cas Number:
- 5580-57-4
- Molecular formula:
- C43H35Cl5N8O6
- IUPAC Name:
- 3,3'-{(2-chloro-5-methyl-1,4-phenylene)bis[imino(1,3-dioxobutane-2,1-diyl)diazene-2,1-diyl]}bis[4-chloro-N-(3-chloro-2-methylphenyl)benzamide]
- Test material form:
- solid: nanoform
- Details on test material:
- Physical state/ appearance: yellow powder
Constituent 1
- Specific details on test material used for the study:
- Batch identification: 0004460012
Supplier: BASF Colors & Effects
CAS No.: 5580-57-4
Purity: 99.3 %
Date of production: 24 Aug 2010
Yellow powder
Administration / exposure
- Route of administration:
- other: test material is in direct contact to the phagolysosomal simulant fluid
- Vehicle:
- other: phagolysosomal simulant fluid (pH 4.5)
- Details on exposure:
- - For static solubility experiment, the medium contained sodium phosphate dibasic anhydrous (Na2HPO4) 142.0 mg/l; sodium chloride (NaCl) 6650 mg/l; sodium sulfate anhydrous (Na2SO4) 71 mg/l; calcium chloride dihydrate (CaCl2. 2H2O) 29 mg/l; glycine (C2H5NO2) 450 mg/l (as representative of organic acids); potassium hydrogen phthalate (1-(HO2C)–2-(CO2K)–C6H4) 4085 mg/l (as ion scavenger); alkylbenzyl-dimethylammonium chloride (ABDC) 50 ppm (as antifungal agent); NaN3 20 mg/l; conditions at 37 ± 0.5°C.
- For dynamic dissolution kinetic experiment, the medium contained sodium phosphate dibasic anhydrous (Na2HPO4) 142.0 mg/l; sodium chloride (NaCl) 6650 mg/l; sodium sulphate anhydrous (Na2SO4) 71 mg/l; calcium chloride dihydrate (CaCl2.2H2O) 29 mg/l; glycine (C2H5NO2) 450 mg/l (as representative of organic acids); potassium hydrogen phthalate (1-(HO2C)–2-(CO2K)–C6H4) 4085 mg/l (as ion scavenger); alkylbenzyl-dimethylammonium chloride (ABDC) 50 ppm (as antifungal agent). The pH is adjusted by 0.1 m HCl to pH 4.5. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- static solubility experiment: 24 hours; dynamic dissolution kinetic experiment: 7 days
- Frequency of treatment:
- one treatment
- Details on study design:
- Pre-treatment:
- To avoid false positive results (detection of additives, impurities, etc.) pigments were purified by sequential solvent washes: first methanol/toluol (80/20), then n-octanol, finally methanol.
- For each solvent the pigment was shaken for 2 hours at room temperature, recovered by centrifugal pelletting (20,000rpm, 1h), and dried under vacuum (100 torr, 90°C, 1h).
- The solvent extracts were analyzed by UV-Vis spectroscopy and discarded.
- Purified pigment samples were used for solubility tests.
Static solubility experiment:
- 1 mg of test substance were suspended in 100 g of the PSF medium in a Schott glass bottle and were dispersed by continuous ultrasonication during 5 h, followed by shaking to ensure homogeneity for a total incubation of 24 h
- The resulting concentration of 10 mg/L was in the range advised for nanomaterial testing by the OECD GD 318 (2020)
- After 24 h, the medium was filtered through a 1 µm glass filter directly followed by a 0.02 µm (= 20 nm) alumina membrane (both of these filter stages are inorganic)
- Thereafter, the filtrates were analyzed by UV-Vis
- Blank controls (no pigment in the dissolution setup) and medium controls (pure medium) were conducted
Dynamic dissolution kinetic experiment:
- Implementaiton of the Continous Flow System (ISO19057:2017), described by Koltermann-Juelly et al. 2018
- Amount of test item: 10 mg solids per flow cell at 2 mL/h fluid flow
- Number of trials: a single flow-cell with up to 14 eluate samplings
- Duration, temperature: the test was performed at 37 ± 0.5 °C for 7 days
- The detection of dissolved fractions provides the ng/cm²/h metric recommended by Oberdörster et al., is grouped in decadic ranges (Koltermann-Jülly et al. 2018). The detection was adapted to organic substances by using UV-Vis spectrometry.
- Oberdörster, G. and T. A. J. Kuhlbusch (2018). "In vivo effects: Methodologies and biokinetics of inhaled nanomaterials." NanoImpact 10(Supplement C): 38-60.
- Koltermann-Jülly, J., J. G. Keller, A. Vennemann, K. Werle, P. Müller, L. Ma-Hock, R. Landsiedel, M. Wiemann and W. Wohlleben (2018). "Abiotic dissolution rates of 24 (nano)forms of 6 substances compared to macrophage-assisted dissolution and in vivo pulmonary clearance: Grouping by biodissolution and transformation." NanoImpact 12: 29-41.
Examinations
- Examinations:
- UV-Vis spectrophotometry was used to analyse dissolved fractions that resulted a) from the sample preparation by impurity extraction solvents in methanol/toluene (80:20), n-octanol and methanol, and b) from the filtered physiological fluids during static or dynamic dissolution testing.
The extracted solvents and the filtered physiological fluids were assessed without dilution, to identify extracted impurities.
- The general procedure followed “UV-VIS Absorption Spectra (spectrophotometric method)”, OECD guideline for Testing of Chemicals, guideline 101, adopted 12th May 1981
- Spectrophotometer: Agilent Cary 5000
- Wavelength range: 200-800 nm
- Cell type: quartz, a) 10.0 mm b) 50.0 mm (to optimize detection down to 0.005 absorbance units)
- Calibration of UV-Vis at peak pigment wavelength for quantification of the dissolved material was performed by dissolving the pigment in concentrated sulfuric acid to get the mass attenuation coefficient
- Blank controls (no test item in the dissolution setup) and medium controls (pure medium) were conducted.
- Limit of Detection (LoD): 0.005 absorbance units
- Limit of Quantification (with the specific attenuation coefficient): 0.01 mg/L
Results and discussion
- Details on results:
- By-products of the test item were removed by extraction with solvents applying the ETAD method 229. The UV-Vis absorption spectra of the extractables did not match the absorption of the test item, indicating that impurities that were chemically not identical to the test item, were successfully removed.
The test item showed a soluble fraction of less than 0.025 mg/L, corresponding to less than 0.25% dissolved fraction and is therefore regarded as insoluble in the static dissolution assay.
Furthermore, the test item showed a dissolution rate of than 0.000 ng/cm²/h. The test item is also considered as insoluble in the dynamic dissolution assay.
Any other information on results incl. tables
Table 1: Results with detection by UV-Vis
| Static dissolution, PSF shaker, dissolved fraction | Dynamic dissolution, Max observed concentration | Dynamic PSF dissolution rate k | Categorization | |
Test item | <0.025 mg/L | <0.25% | 0.002 mg/L | 0.000 ng/cm²/h | insoluble |
Blank control | < 0.1 mg/L | - |
|
|
|
Medium control | < 0.1 mg/L | - |
|
|
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Applicant's summary and conclusion
- Conclusions:
- The test item was identified as insoluble.
- Executive summary:
The static solubility was examined by suspending the test item in phagolysosomal simulant fluid at pH 4.5 for 24h. Thereafter the dissolved fractions were detected by UV-Vis. The test item was insoluble with less than 0.25% dissolved fraction.
The dynamic dissolution assay is an abiotic flow-through method to determine the biodissolution of materials in relevant lung fluids. The flow cell mimics the non-equilibrium physiological conditions, where ions can be transported away from the lungs. A phagolysosomal simulant media with a low pH value (4.5) was used because alveolar macrophages collect and engulf the vast majority of inhaled pulverulent particles from the alveolar surface, and rapidly transfer them into acidic phagolysosomes. The test was performed over seven days, at 37°C. The test item was insoluble with a dissolution rate of 0.000 ng/cm²/h.
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