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EC number: 258-981-8 | CAS number: 54112-23-1
- 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
Additional ecotoxological information
Administrative data
- Endpoint:
- additional ecotoxicological information
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Nov. - Dec. 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD 105 Water Solubility
- Principles of method if other than guideline:
- The objective of the study was to estimate the solubility of the test item Grilbond IL-6 in two different aqueous media used for aquatic toxicity tests to daphnia (reproduction test) and early–life stages of zebrafish. The estimation was made by centrifugation tests.
- GLP compliance:
- yes (incl. QA statement)
- Type of study / information:
- The objective of the study was to estimate the solubility of the test item Grilbond IL-6 in two different aqueous media used for aquatic toxicity tests to daphnia (reproduction test) and early–life stages of zebrafish. The estimation was made by centrifugation tests.
Test material
- Reference substance name:
- N,N'-(methylenedi-p-phenylene)bis[hexahydro-2-oxo-1H-azepine-1-carboxamide]
- EC Number:
- 258-981-8
- EC Name:
- N,N'-(methylenedi-p-phenylene)bis[hexahydro-2-oxo-1H-azepine-1-carboxamide]
- Cas Number:
- 54112-23-1
- Molecular formula:
- C27H32N4O4
- IUPAC Name:
- 2-oxo-N-[4-({4-[(2-oxoazepane-1-carbonyl)amino]phenyl}methyl)phenyl]azepane-1-carboxamide
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- Grilbond IL-6 100%, batch number: 9116211/ 07, purity analysed: 98.71 % w/w - the same sample as used for the OECD 210 and OECD 211 study with the test substance.
Results and discussion
Any other information on results incl. tables
The following results were obtained for samples in Elendt M4 medium.
Sample description |
Replicate |
Concentration of Grilbond IL-6 [µg/L] |
Samples taken from solution 0.512 µg/L at 0 h without centrifugation |
1 |
0.199 |
2 |
0.215 |
|
3 |
0.197 |
|
4 |
0.189 |
|
5 |
0.222 |
|
Samples taken from solution 0.512 µg/L at 0 h after centrifugation |
1 |
< LOQ (0.0384 µg/L) |
2 |
< LOQ (0.0289 µg/L) |
|
3 |
< LOD |
|
4 |
< LOQ (0.0215 µg/L) |
|
5 |
< LOD |
|
Samples taken from solution 0.512 µg/L at 48 h without centrifugation |
1 |
0.333 |
2 |
0.291 |
|
3 |
0.425 |
|
4 |
0.361 |
|
5 |
0.294 |
|
Samples taken from solution 0.512 µg/L at 48 h after centrifugation |
1 |
< LOD |
2 |
< LOD |
|
3 |
< LOD |
|
4 |
< LOD |
|
5 |
< LOD |
|
Samples taken from solution 0.512 µg/L at 72 h without centrifugation |
1 |
0.248 |
2 |
0.188 |
|
3 |
0.226 |
|
4 |
0.173 |
|
5 |
0.145 |
|
Samples taken from solution 0.512 µg/L at 72 h after centrifugation |
1 |
< LOD |
2 |
< LOD |
|
3 |
< LOQ (0.0318 µg/L) |
|
4 |
< LOD |
|
5 |
< LOD |
Limit of quantification (LOQ) = 0.07 µg/L, limit of detection (LOD) = 0.0210 µg/L
The following results were obtained for samples in ISO water.
Sample description |
Replicate |
Concentration of Grilbond IL-6 [µg/L] |
Samples taken from solution 2.56 µg/L at 0 h without centrifugation |
1 |
1.55 |
2 |
1.57 |
|
3 |
1.63 |
|
4 |
1.75 |
|
5 |
1.62 |
|
Samples taken from solution 2.56 µg/L at 0 h after centrifugation |
1 |
0.230 |
2 |
0.156 |
|
3 |
0.159 |
|
4 |
0.216 |
|
5 |
0.193 |
|
Samples taken from solution 2.56 µg/L at 48 h without centrifugation |
1 |
1.77 |
2 |
1.40 |
|
3 |
1.83 |
|
4 |
1.97 |
|
5 |
2.03 |
|
Samples taken from solution 2.56 µg/L at 48 h after centrifugation |
1 |
< LOQ (0.0554 µg/L) |
2 |
< LOQ (0.0456 µg/L) |
|
3 |
< LOQ (0.0542 µg/L) |
|
4 |
< LOQ (0.0378 µg/L) |
|
5 |
0.0762 |
|
Samples taken from solution 2.56 µg/L at 72 h without centrifugation |
1 |
1.86 |
2 |
1.81 |
|
3 |
1.46 |
|
4 |
1.70 |
|
5 |
1.23 |
|
Samples taken from solution 2.56 µg/L at 72 h after centrifugation |
1 |
< LOD |
2 |
< LOD |
|
3 |
< LOQ (0.0322 µg/L) |
|
4 |
< LOD |
|
5 |
< LOQ (0.0211 µg/L) |
Limit of quantification (LOQ) = 0.07 µg/L, limit of detection (LOD) = 0.0210 µg/L
The concentrations of Grilbond IL-6 in both aqueous media were stable over the shaking period of 72 hours in samples analysed without centrifugation.
In centrifuged samples the concentrations were significantly lower, decreasing from the 0 hour sampling to the 72 hour sampling.
The data demonstrate that the practical estimated water solubility of the test item is significantly below 0.512 µg/L in Elendt M4 medium and significantly below 2.56 µg/L in ISO water.
When comparing the analysed concentrations of centrifuged samples at 0 hours, 48 hours and 72 hours, the concentrations in the supernatant were highest at test start.
The concentrations in the supernatant which were defined as the practical estimated limit of water solubility were significantly lower than the concentrations used in the aquatic tests.
Applicant's summary and conclusion
- Conclusions:
- The analysed concentrations in centrifuged samples were significantly lower than in samples analysed without centrifugation, resulting in an estimated practical water solubility of < 0.512 µg/L for Elendt M4 medium and < 2.56 µg/L for ISO water, the test solutions used for the daphnia reproductions study as well as for the fish early-life stage study, respectively.
- Executive summary:
Study Objective: The objective of the study was to estimate the solubility of the test item Grilbond IL-6 in two different aqueous media used for aquatic toxicity tests to daphnia (reproduction test) and early–life stages of zebrafish. The estimation was made by centrifugation tests.
Procedure: The test concentrations equivalent to the nominal No Observed Effect Concentration (NOEC) from parallel daphnia and fish studies were prepared using N,N-dimethylformamid as a solvent.
Each five replicates of 0.512 µg/L in Elendt M4 medium and five replicates of 2.56 µg/L in ISO water were prepared.
Samples were taken directly after application to the test medium. Additional samples were taken after 48 hours and 72 hours of shaking.
From each medium, two sample sets were taken at each sampling interval, one sample set was analysed directly without centrifugation, and samples from the other sample set were centrifuged at 18’000 x g for a period of one hour in “Nalgene” bottles. The bottles were saturated prior to use for 72 hours with a nominal concentration of 0.5 µg/L.
Analytical Method: Directly after sampling, samples were stabilised by addition of acidified acetonitrile and stored deep-frozen until analysis. At the day of analysis, samples were thawed to ambient temperature and analysed by HPLC-MS/MS with a limit of quantification (LOQ) of 0.07 µg/L. and a limit of detection (LOD) of 0.021 µg/L.
Results: For the samples prepared in Elendt M4 medium the analysed concentrations prior to the centrifugation step were within the range from 0.145 µg/L to 0.425 µg/L. After centrifugation for 1 hour at 18000 x g, the concentrations were typically below the LOD, for four samples the concentrations were above the LOD but still below the LOQ. Hence, after removing the particulate matter, the concentration of the supernatant (which might still contain some particles) was below 0.07 µg/L. These data demonstrate that the practical water solubility in Elendt M4 medium (estimated by centrifugation tests) is significantly lower than 0.512 µg/L.
For the samples prepared in ISO water, the analysed concentrations prior to the centrifugation step were within the range from 1.23 µg/L to 2.03 µg/L. After centrifugation for 1 hour at 18’000 x g, the concentrations were typically below the LOQ. Directly after preparation of the solutions (samples taken at 0 hours), the analysed concentrations after centrifugation ranged from 0.156 µg/L to 0.230 µg/L. At 48 hours after preparation and after centrifugation, the analysed concentrations in the supernatant were below the LOQ for four samples and slightly above the LOQ for one sample. At 72 hours after preparation and after centrifugation, the analysed concentrations in the supernatant were below the LOD for three samples and below the LOQ for two samples.
Hence, for this treatment level, it was demonstrated that the concentrations in the supernatant (which were defined to be the practical estimated limit of water solubility) declined with time. It might be speculated that this might be due to the aggregation of very small particles which might have been present at 0 hours and is described in literature (e.g. Young and Buckton 1989). The analysed concentrations in centrifuged samples were significantly lower than in samples analysed without centrifugation, resulting in an estimated practical water solubility of < 0.512 µg/L for Elendt M4 medium and < 2.56 µg/L for ISO water.
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