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Diss Factsheets
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EC number: 227-563-7 | CAS number: 5888-87-9
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline 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:
- other: OECD 487
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- N,N'-hexane-1,6-diylbis(hexahydro-2-oxo-1H-azepine-1-carboxamide)
- EC Number:
- 227-563-7
- EC Name:
- N,N'-hexane-1,6-diylbis(hexahydro-2-oxo-1H-azepine-1-carboxamide)
- Cas Number:
- 5888-87-9
- Molecular formula:
- C20H34N4O4
- IUPAC Name:
- N,N'-hexane-1,6-diylbis(2-oxoazepane-1-carboxamide)
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): BRUGGOLEN M12 / N, N’-hexane-1,6-diylbis(hexahydro-2-oxo-1H-azepine-1-carboxamide)
- Substance type: organic
- Physical state: solid
- Analytical purity: > 99.5%
- Impurities (identity and concentrations): not specified
- Lot/batch No.: 12030701
- Expiration date of the lot/batch: 30 November 2013
- Stability under test conditions: stable
- Storage condition of test material: room temperature
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 1970, 1130, 643, 368, 210, 120, 68.6, 39.2, 22.4 and 12.8 μg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- other: colchicine
- Evaluation criteria:
- A test item will be considered as clearly positive in this assay, if the following criteria are met:
(i)
Significant increases in the proportion of micronucleated cells over the concurrent controls occur at one or more concentrations.
(ii)
The proportion of micronucleated cells at such data points exceeds the normal range. If the increases fall within the range of values, normally observed in the negative control cultures, the test item cannot be classified as positive. Any significant increases over the concurrent negative controls will therefore be compared with historical control values derived from recent studies.
(iii) There is a significant dose-relationship.
Results which only partially satisfy the above criteria will be dealt with on a case-by-case basis. Similarly, positive responses, seen only at high levels of cytotoxicity, will require careful interpretation when assessing their biological significance. - Statistics:
- The numbers of binucleated cells with micronuclei in the control and treated cultures will be compared using an appropriate statistical method. The solvent controls will be used as the reference point for comparison in the statistical evaluation and the evaluation of the results.
Results and discussion
Test results
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Cytotoxicity above 253 ug/mL in the absence and presence of S9 metabolism.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Following treatment with the test item, no remarkable variation of pH over the control values was observed in the absence or presence of S9 metabolism.
- Effects of osmolality: Following treatment with the test item, no remarkable variation of osmolality over the control values was observed in the absence or presence of S9 metabolism. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
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Presence of S9 metabolism |
Absence of S9 metabolism |
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Treatment |
Dose level |
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µg/mL |
%Mn cells |
Sig. |
%Cytotoxicity |
%Mn cells |
Sig. |
%Cytotoxicity |
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Untreated |
0.0 |
1.00 |
|
15 |
0.60 |
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3 |
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Solvent 1% |
0.0 |
1.05 |
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0 |
0.60 |
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0 |
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Test item |
176 |
- |
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- |
0.65 |
NS |
22 |
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Test item |
211 |
1.35 |
NS |
18 |
1.10 |
NS |
22 |
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Test item |
253 |
11.0 |
*** |
35 |
3.60 |
*** |
58 |
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Test item |
311 |
13.1 |
*** |
64 |
- |
- |
- |
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Mitomycin-C |
0.300 |
- |
- |
- |
5.70 |
*** |
19 |
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Colchicine |
2.50 |
- |
- |
- |
8.90 |
*** |
§ |
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Cyclophosphamide |
10.0 |
5.80 |
*** |
52 |
- |
- |
Key:
%Mn cells : Percentage of cells bearing micronuclei
Sig. : Statistical significance
NS : Not significant
- : Not tested or not selected for scoring
* : Statistically significant at p<0.05
** : Statistically significant at p<0.01
*** : Statistically significant at p<0.001
§ : not calculated - induction of multinucleation was attributable to multipolar division as a
consequence of induction of multipolar spindles
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
positive
annex VIII, 8.4 - Executive summary:
On the basis of the results obtained, it is concluded that BRUGGOLEN M12 induces micronuclei in Chinese hamster V79 cells after in vitro treatment in the absence and presence of S9 metabolic activation, under the reported experimental conditions.
Therefore, according to ECHA's guidance R.7a "Endpoint specific guidance", no second in vitro testing has to be performed but a testing proposal for an in vivo testing (REACH Annex IX) has to be submitted (see section 7.6.2).
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.