Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 941-628-3 | CAS number: 1263184-87-7
- 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:
- 10 Dec 2013 to 13 Jan 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Version / remarks:
- August 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 30 May 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- rac-(1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one
- EC Number:
- 941-628-3
- Cas Number:
- 1263184-87-7
- Molecular formula:
- C12H14Cl2O2
- IUPAC Name:
- rac-(1R,4S,4aR,8R,8aS)-9-(dichloromethylidene)-8-hydroxyoctahydro-1,4-methanonaphthalen-5(1H)-one
- Test material form:
- solid
Constituent 1
Method
- Target gene:
- His-locus and Trp-locus
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A pKM 101
- Species / strain / cell type:
- E. coli, other: WP2 pKM 101
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/ß-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- Range in plate incorporation test (experiment I) and the pre-incubation test (experiment II): 3, 10, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Justification for top dose: 5000 μg/plate is the maximum recommended dose according to the test guideline - Vehicle / solvent:
- - Solvent used: DMSO (purity 99%)
- Justification for choice of solvent: The solvent was chosen because of its solubilisation properties and its relative non-toxicity to the bacteria.
Controls
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- methylmethanesulfonate
- other: 4-nitro-o-phenylene-diamine, 4-NOPD and 2-aminoanthracene, 2-AA
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
Experiment I: in agar (plate incorporation)
Experiment II: preincubation
DURATION
- Preincubation period: 60 min (experiment II only)
- Exposure duration: 72 hours
NUMBER OF REPLICATIONS: 2 independent experiments, each using 3 replicates
DETERMINATION OF CYTOTOXICITY
- Method: a reduction in the number of spontaneous revertants (below a factor of 0.5) or a clearing of the bacterial background lawn - Evaluation criteria:
- ACCEPTABILITY OF THE ASSAY
The Salmonella typhimurium and Escherichia coli reverse mutation assay is considered acceptable if it meets the following criteria:
- regular background growth in the negative and solvent control
- the spontaneous reversion rates in the negative and solvent control are in the range of the historical data
- the positive control substances should produce a significant increase in mutant colony frequencies
- a minimum of five analysable concentrations should be present with at least four showing no signs of toxic effects, evident as a reduction in the number of revertants below an induction factor of 0.5.
EVALUATION OF RESULTS
A test substance is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice the colony count of the corresponding solvent control is observed.
A concentration-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 concentration-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.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium, other: TA1537, TA1535, TA100, TA98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli, other: WP2 uvrA pKM101, WP2 pKM101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST SPECIFIC CONFOUNDING FACTORS
Precipitation: The test substance precipitated in the overlay agar of the test tubes from 2500 to 5000 μg/plate with and without S9 mix in both experiments. Precipitation of the test substance in the overlay agar on the incubated agar plates was observed at 2500 and 5000 μg/plate in experiment I and II. The undissolved particles had no influence on data recording.
NUMBER OF REVERTANT COLONIES
No increase in revertant colony numbers of any of the six tester strains was observed following treatment with the test substance at any concentration, 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.
(HISTORICAL) CONTROL DATA
- The number of colonies did not quite reach the lower limit of the laboratories historical control range in the untreated and solvent control of strain WP2 uvrA pKM101 with S9 mix in experiment II. Since these deviations are rather small, they are judged to be based on biologically irrelevant fluctuations in the number of colonies and have no impact on the outcome of the study.
- Appropriate reference mutagens were used as positive controls. They showed a distinct increase of induced revertant colonies.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
Cytotoxicity: Reduced background growth and toxic effects were observed at concentrations (μg/plate) shown in Table 1 and 2 in 'Any other information on results incl. tables', respectively. The pre-experiment is reported as experiment I as at least five concentrations were analysable and the criteria under "Acceptability of the assay" were met.
Any other information on results incl. tables
Table 1. Reduced background growth
Strain |
Experiment I |
Experiment II |
||
|
without S9 mix |
with S9 mix |
without S9 mix |
with S9 mix |
TA 1535 |
2500, 5000 |
2500, 5000 |
/ |
/ |
TA 1537 |
2500, 5000 |
2500, 5000 |
/ |
1000 - 5000 |
TA 98 |
2500, 5000 |
2500, 5000 |
/ |
2500, 5000 |
TA 100 |
2500, 5000 |
2500, 5000 |
1000 - 5000 |
1000 - 5000 |
WP2 pKM101 |
2500, 5000 |
2500, 5000 |
2500, 5000 |
5000 |
WP2 uvrA pKM101 |
2500, 5000 |
2500, 5000 |
/ |
/ |
/ = no reduction of the background growth observed
Table 2. Toxic effects, evident as a reduction in the number of revertants (below an induction factor of 0.5)
Strain |
Experiment I |
Experiment II |
||
|
without S9 mix |
with S9 mix |
without S9 mix |
with S9 mix |
TA 1535 |
5000 |
/ |
5000 |
2500, 5000 |
TA 1537 |
/ |
5000 |
5000 |
5000 |
TA 98 |
5000 |
2500, 5000 |
5000 |
5000 |
TA 100 |
5000 |
5000 |
2500, 5000 |
1000 - 5000 |
WP2 pKM101 |
5000 |
5000 |
2500, 5000 |
2500, 5000 |
WP2 uvrA pKM101 |
5000 |
/ |
/ |
5000 |
/ = no toxic effects observed
Applicant's summary and conclusion
- Conclusions:
- During a GLP-compliant OECD 471 mutagenicity tests and under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. The test substance is considered to be non-mutagenic in the Salmonella typhimurium and Escherichia coli reverse mutation assay.
- Executive summary:
This GLP-compliant OECD 471 study was performed to investigate the potential of the test substance to induce gene mutations in the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100, and the Escherichia coli strains WP2 uvrA pKM101 and WP2 pKM101. The assay was performed with and without Phenobarbital/ß-naphthoflavone induced rat liver S9 metabolic activation. Each concentration, including the controls, was tested in triplicate. The test substance was tested at the following concentrations: Experiment I and II: 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate.
The plates incubated with the test substance showed reduced background growth at higher concentrations with all strains used in the first experiment and some of the strains in the second experiment. Cytotoxic effects, evident as a reduction in the number of revertants (below an induction factor of 0.5), were observed at high concentrations in nearly all strains used. No increase in revertant colony numbers of any of the six tester strains was observed following treatment with the test substance at any concentration 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. Appropriate reference mutagens were used as positive controls. They showed a distinct increase of induced revertant colonies.
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test substance is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
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.
