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EC number: 221-374-3 | CAS number: 3081-01-4
- 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
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- no mitotic index determined but MTD reached; 3 times 50 instead of 2 times 100 cells scored
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- N-(1,4-dimethylpentyl)-N'-phenylbenzene-1,4-diamine
- EC Number:
- 221-374-3
- EC Name:
- N-(1,4-dimethylpentyl)-N'-phenylbenzene-1,4-diamine
- Cas Number:
- 3081-01-4
- Molecular formula:
- C19H26N2
- IUPAC Name:
- N1-(5-methylhexan-2-yl)-N4-phenylbenzene-1,4-diamine
- Details on test material:
- Santoflex 14
Constituent 1
Method
- Target gene:
- chromosome aberrations
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix, S9 from Aroclor 1254-induced rat liver homogenate (S9)
- Test concentrations with justification for top dose:
- pre-test I(+/-S9): 5, 20, 50, 100, 200, 500, 1000, 2000, 5000 µg/mL; pre-test II (+/-S9): 1, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, 20 µg/mL,
main experiment I (+/-S9): 0, 7.5, 10, 15 µg/mL, main experiment II (-S9): 7.5, 10 µg/mL;
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- methylmethanesulfonate
Results and discussion
Test results
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- other: solvent aceton induced a relative high number of aberrant cells in main experiment I
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: strain/cell type: Chinese hamster Ovary (CHO)
Any other information on results incl. tables
1. Range-Finding Experiments:
CHO cells were treated with 5 to 5000 µg/mL of SANTOFLEX 14 both in the presence and absence of activation. The cells were scored for both mitotic index and average cell generation time and compared to the solvent (acetone) control. The average cell generation time for the solvent control was approximately 12 hours for both with and without activation, with a mitotic index of 5 to 8 %. Cytotoxic effects were observed at 20 µg/ml both in the absence and presence of activation as indicated by a sharp reduction in mitotic index and an extended average generation time.
The cytotoxicity of SANTOFLEX 14 was further defined in a second range-finding experiment where concentrations ranged from 1 to 20 µg/mL with and without activation. The cells were scored for both mitotic index and average cell generation time. Cytotoxic effects were observed at 12.5 µg/ml and higher concentrations in the absence and presence of activation as indicated by an extended average generation time (-S9 20.3 h at 12.5 µg/ml vs. 12.0 control; +S9: at 12.5 µg/ml 15.2 h vs. 12.7 control).
Based on the range-finding experiments, the highest concentrations of SANTOFLEX 14 tested were 15 µg/mL with and without activation. The harvest times were 12 and 24 hours for 1.5, 5, 7.5 and 10 µg/mL with and without activation, 18 and 36 hours for 15 µg/mL with activation and 24 and 48 hours for 15 µg/mL without activation. The harvest times were chosen to represent approximately 1X and 2X that of the cell generation times.
2. Cytogenetics Studies:
A. Without activation: The SANTOFLEX 14 levels of 7.5, 10 and 15 µg/mL were chosen as the highest three scorable doses.
Statistically significant increases in number of cells with structural aberrations (12 cells with aberrations vs. 3 cells with aberrations solvent control) and average structural aberrations per cell (0.060 vs. 0.015 solvent control) were observed at the 15 µg/mL dose level for the 48 hour harvest time (% aberrant cells: 6 % vs. 1.5 % solvent control) and for average structural aberrations per cell for the 24 hour harvest time (0.120 vs. 0.045 solvent control). A significant dose-response was not observed.
B. With activation: The SANTOFLEX 14 dose levels of 7.5, 10 and 15 µg/mL were selected as the three highest scorable doses. Statistically significant increases in the number of cells with structural aberrations (at 10 µg/mL 39 vs. 15 solvent control) and average structural aberrations per cell (10 µg/mL: 0.383 vs. 0.090 solvent control) were observed for the 10 µg/mL dose level (% aberrant cells: 19.9 % vs. 7.5 % solvent control) and for the number of cells with aberrations at the 7.5 µg/mL dose level for the 12 hour harvest time (at 7.5 µg/mL 29 cells with aberrations vs. 15 cells with aberration solvent control). A dose-related response was not observed.
C. Retest: Because of the relatively high aberration levels (-S9: 10 %, +S9: 7.5 %) for the 12 hour harvest time in the solvent control, the experiment was repeated using dose levels of 7.5 and 10 µg/mL with and without activation. The 24 and 48 hour harvests were not repeated as the solvent background was low and therefore the statistically significant response of the 15 µg/mL dose level without activation was concluded to be treatment induced. The 10 µg/mL dose level with activation was again statistically significant for the number of cells with aberrations (17 cells with aberrations vs. 6 cells solvent control) and for structural aberrations per cell (0.090 vs. 0.030 solvent control) A dose-response relationship was not observed.
Conclusion:
Without activation, a statistically significant increase in aberration frequency was observed for the 15 µg/mL dose level. In the presence of activation, a statistically significant response was observed at the 10 µg/mL dose level for the 12 hour harvest.
A significant dose-response relationship was not observed. The retest experiment confirmed the statistically significant response of the 10 µg/mL dose level in the presence of activation. A significant dose-response was not observed.
The authors suggested that the observed effects might be secondary because the effects were observed in the range of cytotoxicity indicated by an increased generation time (10 µg/mL +S9: pre-experiment: 13.7h vs. 12.7 h solvent control, 15 µg/mL -S9: 22.0 h vs. 12.1 h solvent control) and in addition because of a lack of a dose response relationship.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: positive
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