Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 205-273-1 | CAS number: 137-03-1
- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 September 2016 - 02 December 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 26 September 2014
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 30 may 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- other: Mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- 2-heptylcyclopentanone
- EC Number:
- 205-273-1
- EC Name:
- 2-heptylcyclopentanone
- Cas Number:
- 137-03-1
- Molecular formula:
- C12H22O
- IUPAC Name:
- 2-heptylcyclopentan-1-one
- Test material form:
- liquid
1
Test animals
- Species:
- mouse
- Strain:
- other: Hsd: ICR (CD-1®)
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Envigo, B.V., Horst, The Netherlands
- Age at study initiation: approximately six to ten weeks
- Weight at study initiation: 23 to 30 g
- Assigned to test groups randomly: yes
- Fasting period before study: no data
- Housing: The animals were housed in groups of five in solid-floor polypropylene cages with wood-flake bedding.
- Diet: Free access to food (Envigo Teklad 2014C Global Certified Rodent Diet supplied by Envigo Laboratories UK Ltd., Oxon, UK)
- Water: Free access to mains drinking water
- Acclimation period: minimum of five days
ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): approximately fifteen
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle used: arachis oil
- Justification for choice of solvent/vehicle: no data - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was freshly prepared as required as a solution at the appropriate concentration in arachis oil. The test item was formulated within two hours of it being applied to the test system; it is assumed that the formulation was stable for this duration.
VOLUME: 10 mL/kg bw - Duration of treatment / exposure:
- 24 and 48 hours
- Frequency of treatment:
- Dosed once.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw (total dose)
- Remarks:
- 24 hours exposure time
- Dose / conc.:
- 150 mg/kg bw (total dose)
- Remarks:
- 24 hours exposure time
- Dose / conc.:
- 300 mg/kg bw (total dose)
- Remarks:
- 24 hours exposure time
- Dose / conc.:
- 600 mg/kg bw (total dose)
- Remarks:
- 24 and 48 hours exposure time
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide:
- Route of administration: orally at 50 mg/kg bw
- Doses / concentrations: Dissolved in sterile distilled water at a concentration of 5 mg/mL
Examinations
- Tissues and cell types examined:
- The incidence of micronucleated cells per 4000 polychromatic erythrocytes (PCE-blue stained immature cells) per animal was scored. In addition, the number of normochromatic erythrocytes (NCE-pink stained mature cells) associated with 1000 erythrocytes was counted; these cells were also scored for incidence of micronuclei.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Based on the observed mortality and clinical signs in the toxicity assay, dose levels were selected for the micronucleus assay.
DETAILS OF SLIDE PREPARATION: Immediately following termination (i.e. 24 or 48 hours following dosing), both femurs were dissected from each animal, aspirated with foetal bovine serum and bone marrow smears prepared following centrifugation and re-suspension. The smears were air-dried, fixed in absolute methanol, stained in May-Grünwald / Giemsa, allowed to air-dry and a cover slip applied using mounting medium.
METHOD OF ANALYSIS: Stained bone marrow smears were coded and examined blind using light microscopy at x1000 magnification. The incidence of micronucleated cells per 4000 polychromatic erythrocytes (PCE-blue stained immature cells) per animal was scored. Micronuclei are normally circular in shape, although occasionally they may be oval or half-moon shaped, and have a sharp contour with even staining. In addition, the number of normochromatic erythrocytes (NCE-pink stained mature cells) associated with 1000 erythrocytes was counted; these cells were also scored for incidence of micronuclei.
The ratio of polychromatic to normochromatic erythrocytes was calculated together with appropriate group mean values and standard deviations. - Evaluation criteria:
- Comparison was made between the number of micronucleated polychromatic erythrocytes occurring in each of the test item groups and the number occurring in the vehicle control group.
A positive mutagenic response is demonstrated when a statistically significant, dose-responsive, toxicologically relevant increase in the number of micronucleated polychromatic erythrocytes is observed for either the 24 or 48-hour kill times when compared to the vehicle control group.
If these criteria were not fulfilled, then the test item was considered to be non-genotoxic under the conditions of the test.
A positive response for bone marrow toxicity was demonstrated when the dose group mean polychromatic to normochromatic ratio was shown to be statistically significantly lower than the vehicle control group. - Statistics:
- All data were statistically analysed using appropriate statistical methods as recommended by the UKEMS Sub-committee on Guidelines for Mutagenicity Testing Report, Part III (1989).
The data was analysed following a transformation using Student's t-test (two tailed).
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Clinical signs of toxicity were observed at 600 mg/kg bw (24 and 48-hour) and included hunched posture and ptosis.
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: Groups of mice were dosed orally as follows: 1000 mg/kg bw (3 males and 1 female), 800 mg/kg bw (2 male) and 600 mg/kg bw (4 males and 2 females).
The clinical signs of hunched posture, lethargy, ataxia, ptosis, decreased respiration and labored respiration was observed at 1000 mg/kg bw. One of the animals dosed at 1000 mg/kg bw exceeded the severity band therefore was killed in extremis. The dose level was decreased to 800 mg/kg bw and the clinical signs of hunched posture, ptosis, ataxia and tiptoe gait were observed. The clinical signs were considered to be too severe and therefore the dose level was reduced to 600 mg/kg bw. The following clinical signs were observed, hunched posture, and ptosis. This was selected as the considered maximum tolerated dose level and the main test was initiated using this dose level. Acceptable bone marrow toxicity was observed at 600 mg/kg bw.
RESULTS OF DEFINITIVE STUDY
- Mortality Data and Clinical Observations:
There were no premature deaths in any of the dose groups. Clinical signs of toxicity were observed at 600 mg/kg bw (24 and 48-hour) and included hunched posture and ptosis. The clinical signs were considered to be indicative of systemic absorption.
- Evaluation of Bone Marrow Slides:
The test item Fleuramone did not show any indication of toxicity to bone marrow. The PCE/NCE ratio had no marked reductions when compared to the vehicle control. No statistically significant, decreases in the PCE/NCE ratio were observed in any of the exposure groups when compared to the vehicle control.
There was no evidence of any significant increases in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test item when compared to the vehicle control group.
The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the sensitivity of the system to the known mutagenic activity of cyclophosphamide under the conditions of the test.
Applicant's summary and conclusion
- Conclusions:
- A micronucleus study with the substance was performed equivalent to OECD 474 guideline and GLP principles, in male mice. It is concluded that the substance is not mutagenic in the mouse micronucleus assay.
- Executive summary:
In an in vivo micronucleus study, male mice were exposed to 150, 300 and 600 mg/kg bw of the substance, performed equivalent to OECD 474 guideline and GLP principles. Based on the results of the range finding test in which clinical signs of hunched posture, lethargy, ataxia, ptosis, decreased respiration and labored respiration were observed at 1000 mg/kg. One of the animals dosed at 1000mg/kg exceeded the severity band therefore was killed in extremis. The dose level was decreased to 800mg/kg and the clinical signs of hunched posture, ptosis, ataxia and tiptoe gait were observed. The clinical signs were considered to be too severe and therefore the dose level was reduced to 600 mg/kg. The following clinical signs were observed, hunched posture, and ptosis. This was selected as the considered maximum tolerated dose level and the main test was initiated using this dose level. At this dose levels and below there were no premature deaths in any of the dose groups. Clinical signs of toxicity were observed at 600 mg/kg bw (24 and 48-hour) and included hunched posture and ptosis. There was no evidence of any significant increases in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test substance when compared to the vehicle control group. The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the sensitivity of the system to the known mutagenic activity of cyclophosphamide under the conditions of the test. It is concluded that the substance is not mutagenic in the mouse micronucleus 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.