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EC number: 605-398-5 | CAS number: 16524-65-5
- 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 bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2006-05-11 to 2006-05-29
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Non-GLP study performed according to the OECD Guideline 471 (Bacterial Reverse Mutation Assay) with the following deviations: only three strains are tested. However, an expert statement is added in the field "any other remarks" to justify the fact that no further testing is necessary.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- only 3 bacterial strains tested instead of 5
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Directive 2000/32/EC, L1362000, Annex 4D (dated 2000-05-19)
- Deviations:
- no
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- (2S)-2-[(1S,2R,6S,14R,15R,16R)-3-(cyclopropylmethyl)-11,15-dimethoxy-13-oxa-3-azahexacyclo[13.2.2.1²,⁸.0¹,⁶.0⁶,¹⁴.0⁷,¹²]icosa-7,9,11-trien-16-yl]-3,3-dimethylbutan-2-ol
- Cas Number:
- 16524-65-5
- Molecular formula:
- C30H43NO4
- IUPAC Name:
- (2S)-2-[(1S,2R,6S,14R,15R,16R)-3-(cyclopropylmethyl)-11,15-dimethoxy-13-oxa-3-azahexacyclo[13.2.2.1²,⁸.0¹,⁶.0⁶,¹⁴.0⁷,¹²]icosa-7,9,11-trien-16-yl]-3,3-dimethylbutan-2-ol
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material (as cited in study report): JNJ-18163678-AAA (T002713)
- Physical state: solid (powder)
- Appearance: White powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch No.: 00477910 RT002713G4A051
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Not indicated by the sponsor
OTHER SPECIFICS:
- Name of test material (as cited in study report): T2713
- Molecular formula (if other than submission substance): C30H43NO4
- Molecular weight (if other than submission substance): 481.68 g/mol
- Substance type: White
- Physical state: Solid
- Analytical purity: 100%
- Other: Chemical name: 6,14-Ethenomorphinan-7-methanol, 17-(cyclopropylmethyl)-a-(1,1-dimethylethyl)-4,5-epoxy-18,19-dihydro-2,6-dimethoxy-amethyl-,(aS,5a,7a)-
Method
- Target gene:
- The histidine dependent strains were derived from S. typhimurium strain LT2 through a mutation in the histidine locus.
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 98
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 100
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 102
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/beta-Naphtoflavone induced rat liver S9 from male Wistar Hanlbm rats
- Test concentrations with justification for top dose:
- Experiment I (pre-experiment): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate with and without S9-mix
Experiment II: 33, 100, 333, 1000, 2500 and 5000 µg/platewith and without S9-mix
In the pre-experiment, the maximum recommended dose of 5000 µg/plate was chosen as the highest dose level. Based on the results of the pre-experiment, 5000 µg/plate was chosen as the highest dose level for Experiment II. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was chosen because of its solubility properties and its relative non-toxicity to the bacteria. On the day of the experiment, the test item T2713 was dissolved in DMSO (purity > 99 %)
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA100, without metabolic activation, 10 µg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine (4-NOPD)
- Remarks:
- TA98, without metabolic activation, 10 µg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- TA102, without metabolic activation, 4.0 µL/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene (2-AA)
- Remarks:
- All strains, with metabolic activation,2.5 µg/plate (TA98 and TA100), 10.0 µg/plate (TA102)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Experiment I: plate incorporation; Experiment II: preincubation
DURATION
- Preincubation period: 60 minutes
- Exposure duration: 48 hours
- Selection time (if incubation with a selection agent): 48 hours (simultaneous with exposure)
SELECTION AGENT (mutation assays): Histidine
NUMBER OF REPLICATIONS: For each strain and dose level, including the controls three plates were used.
DETERMINATION OF CYTOTOXICITY: To evaluate the toxicity of the test item a pre-experiment was performed with all strains used. Eight concentrations were tested for toxicity and mutation induction with each 3 plates. The experimental conditions in this pre-experiment were the same as described for experiment I (plate incorporation test).
Toxicity of the test item can be evident as a reduction in the number of spontaneous revertants or a clearing of the bacterial background lawn.
OTHER: The colonies were counted using the Petri Viewer Mk2 with the software program Ames Study Manager. The counter was connected to an IBM AT compatible PC with printer which printed out both the individual and mean values of the plates for each concentration together with standard deviations and enhancement factors as compared to the spontaneous reversion rates. Due to precipitation of the test item some plates were counted manually. - Evaluation criteria:
- Evaluation of the results:
- A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 98, TA 100, and TA 102) the colony count of the corresponding solvent control is observed.
- A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration.
- An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.
- A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. However, whenever the colony counts remain within the historical range of negative and solvent controls such an increase is not considered biologically relevant. - Statistics:
- A statistical analysis of the data is not required
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- minor toxic effects at 5000µg/plate in Experiment I without S9-mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- minor toxic effects at 2500µg/plate in Experiment I without S9-mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: precipitation occurred at 1000, 2500 and 5000 µg/plate with and without S9, for all strains, in both experiment I and experiment II
RANGE-FINDING/SCREENING STUDIES:
In the pre-experiment the concentration range of the test item was 3 – 5000 µg/plate. The pre-experiment is reported as experiment I since no relevant toxic effects were observed six concentrations were tested in experiment II and 5000 µg/plate were chosen as maximum concentration.
ADDITIONAL INFORMATION ON CYTOTOXICITY: The plates incubated with the test item showed normal background growth up to 5000 µg/plate with and without metabolic activation in both independent experiments.
Any other information on results incl. tables
No substantial increase in revertant colony numbers of any of the three tester strains was observed following treatment with T2713 at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results:
negative with and without metabolic activation
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
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