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EC number: 940-673-6 | CAS number: 1391764-61-6
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from 17 January 2013 to 25 February 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented guideline and GLP study
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Principles of method if other than guideline:
- Not relevant
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- K-36
- IUPAC Name:
- K-36
- Reference substance name:
- N,N-dibutyl-4-[4-(4-chlorophenyl)-3,6-dioxo-2H,3H,5H,6H-pyrrolo[3,4-c]pyrrol-1-yl]benzamide
- Cas Number:
- 1391764-61-6
- Molecular formula:
- C27H28ClN3O3
- IUPAC Name:
- N,N-dibutyl-4-[4-(4-chlorophenyl)-3,6-dioxo-2H,3H,5H,6H-pyrrolo[3,4-c]pyrrol-1-yl]benzamide
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Constituent 2
Method
Species / strain
- Species / strain / cell type:
- mammalian cell line, other: CHL/IU
- Metabolic activation:
- with and without
- Metabolic activation system:
- from commercially available rat liver S9 induced with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- 9.34, 18.7, 37.3, 74.7, 149, 299, 598, 1200, 2390, 4780 µg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: 1% CMC (carboxymethyl cellulose)
- Justification for choice of solvent/vehicle: 1% CMC was selected because it is available for treatment of highest dose of the test substance (up to 10 mM).
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period:
- Exposure duration: 6 hours (short-term treatment) or 24 hours (long-term treatment)
- Expression time (cells in growth medium): 18 hours (short-term treatment) or 0 hour (long-term treatment)
- Fixation time: 2 hours before harvesting of the cells
SPINDLE INHIBITOR (cytogenetic assays): colcemid
STAIN (for cytogenetic assays): Giemsa solution
NUMBER OF REPLICATES: 2
NUMBER OF CELLS EVALUATED: 100 cells per slide (200 per dose level)
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth - Evaluation criteria:
- If the following criteria for the frequency of the cells with structural aberrations (excluding gap) were met, the potentiality of the test substance to induce structural aberrations was judged to be equivocal (from 5 to 9%) or positive (10% or more):
1) 5% or more
2) statistically significant increase in a dose-dependent manner as compared with the negative control
For thenumerical aberrations, the potentiality of the test substance to induce numerical aberrations was judged to be positive in cases where the frequency of cells with polyploidy was statistically significantly increased in a dose-dependent manner as compared with the negative control group. - Statistics:
- not performed
Results and discussion
Test results
- Species / strain:
- mammalian cell line, other: CHL/IU
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH, Effects of osmolality, Evaporation from medium, Water solubility: no data
- Precipitation: the precipitates of the test substance were observed at the dose levels of 299 µg/mL or more in all treatment methods.
COMPARISON WITH HISTORICAL CONTROL DATA: no data - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Treatment time |
Concentration (µg/mL) |
Relative cell growth (%) |
Number of cells showing structural aberrations (SA) |
Number of cells showing numerical aberrations (NA) |
Final judgment |
|||
observed |
Total % |
observed |
Total % |
SA |
NA |
|||
6 hr S9 mix (-) |
0 |
100 |
200 |
1.0 |
200 |
0.3 |
|
|
37.5 |
81.0 |
Not observed |
Not observed |
- |
- |
|||
75.0 |
88.1 |
200 |
2.5 |
200 |
1.0 |
|||
150 |
88.5 |
200 |
2.0 |
200 |
0.5 |
|||
300 |
80.5 |
200 |
2.0 |
200 |
0.5 |
|||
MMC 0.05 |
- |
200 |
26.0 |
200 |
0.5 |
+ |
- |
|
6 hr S9 mix (+) |
0 |
100 |
200 |
2.0 |
200 |
0.3 |
|
|
37.5 |
106.8 |
Not observed |
|
Not observed |
0.0 |
- |
- |
|
75.0 |
97.4 |
200 |
0.0 |
200 |
0.3 |
|||
150 |
106.8 |
200 |
1.5 |
200 |
0.0 |
|||
300 |
107.3 |
200 |
2.0 |
200 |
0.3 |
|||
MMC 0.05 |
- |
200 |
28.5 |
200 |
1.0 |
+ |
- |
|
24 hr |
0 |
100 |
200 |
2.0 |
200 |
0.8 |
|
|
37.5 |
104.7 |
200 |
1.5 |
200 |
0.3 |
- |
- |
|
75.0 |
93.3 |
200 |
1.0 |
200 |
0.3 |
|||
150 |
100.0 |
200 |
0.5 |
200 |
0.0 |
|||
300 |
83.1 |
Not observed due to excessive precipitation |
||||||
MMC 0.05 |
- |
200 |
30.5 |
200 |
0.0 |
+ |
- |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
Under the experimental conditions, K-36 does not show mutagenic activity in the mammalian cell chromosomal aberration test with CHL/IU cells. - Executive summary:
In a mammalian cell cytogenetics assay (chromosome aberration assay) performed according to OECD guideline 473 and GLP, CHL/IU cells were exposed to K-36 in 1% CMC, at concentrations of 9.34 to 4780 µg/mL with and without metabolic activation. K-36 was tested up to precipitating concentrations and the dose-levels selected for metaphase analysis were 37.5, 75, 150 and 300 µg/mL.
The precipitates of the test substance were observed at the dose levels of 299 µg/mL or more in all treatment methods.Positive controls induced the appropriate response.
There was no evidence of chromosome aberration induced over background. In all treatment methods, no celle growth inhibition was observed and the IC50 values exceeded 4780 µg/mL.Therefore, K-36 is considered to be non-clastogenic in this chromosome aberration test when tested up to precipitating concentrations.
This study is classified as acceptable. This study satisfies the requirement for OECD guideline 473 for in vitro cytogenetic mutagenicity data.
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