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EC number: 204-977-6 | CAS number: 130-15-4
- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow 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:
- 1 987
- Report date:
- 1987
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Version / remarks:
- 1983 version
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EEC Directive 84/449
- Version / remarks:
- 1984 version
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of assay:
- mammalian bone marrow chromosome aberration test
Test material
- Reference substance name:
- 1,4-naphthoquinone
- EC Number:
- 204-977-6
- EC Name:
- 1,4-naphthoquinone
- Cas Number:
- 130-15-4
- Molecular formula:
- C10H6O2
- IUPAC Name:
- 1,4-naphthoquinone
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- hamster, Chinese
- Strain:
- not specified
- Details on species / strain selection:
- Detailed as EMD (brother-sister inbreeding)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: E. Merck, Darmstadt
- Age at study initiation: 7 to 9 weeks
- Weight at study initiation: 44.2 g (males) and 37.6 g (females)
- Assigned to test groups randomly: yes
- Fasting period before study: No
- Housing: Housed individually in Makrolon cages type 1 on softwood chippings under conventional conditions.
- Diet (e.g. ad libitum): Ad libitum (free access to ssniff hamster mixed food.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 29°C
- Humidity (%): 33 to 71%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: 0.25% aqueous Methocel K4M Premium
- Justification for choice of solvent/vehicle: Standard vehicle
- Concentration of test material in vehicle: Not specified
- Amount of vehicle (if gavage or dermal): Not specified - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosed via oral gavage - Duration of treatment / exposure:
- Single dose for all relevant animals (1 day)
- Frequency of treatment:
- Once on day of treatment
- Post exposure period:
- 6 to 48 hours
Doses / concentrationsopen allclose all
- Dose / conc.:
- 15 mg/kg bw/day
- Dose / conc.:
- 40 mg/kg bw/day
- Dose / conc.:
- 120 mg/kg bw/day
- No. of animals per sex per dose:
- 5 males and 5 females per dose group (70 in total). Any animals that died during the study were replaced with those from the same stock. At 3 hours before sacrifice and bone marrow sampling, the animals were treated with colcemide to arrest dividing bone marrow cells in the metaphase.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Name: Endoxan (Cyclophosphamide).
- Justification for choice of positive control(s): Standard positive control
- Route of administration: Oral gavage
- Doses / concentrations: 20 mg dissolved in 10 mL Aqua pro injectione directly before use. A dose of 20 mg/kg was used on study.
Examinations
- Tissues and cell types examined:
- Bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Based on results of a preliminary study.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Bone marrow sampled at 24 hours post dose in animals receiving 15 or 40 mg/kg and 6, 24 and 48 hours post dose in animals receiving 120 mg/kg. Positive control animals were sampled at 24 hours post dose.
DETAILS OF SLIDE PREPARATION: Immediately after the hamsters were euthanized by CO2, both femora of each animal were dissected, cleaned from the rest of teh muscles and the epiphyses removed. bone marrow cells from both the femora per animal were flushed out withs aline and collected in a centrifuge tube and suspended. After centrifugation the supernatant was drawn off and the sediment suspended in KCl solution at 37°C. After hypotonic treatment for 10 minutes, the cells were futher centrifuged and the supernatant discarded. The cells were fixed twice in a mixture of acetic acid and methanol, dropped onto the slides in fresh fixative and flame dried. After over-night air drying at room temperature the slides were stained with aceto-orcein solution, differentiated in ethanol dipped twice in xylene and mounted in Eukitt.
METHOD OF ANALYSIS: All slides were coded before microscopic examination to ensure a lack of bias. 100 metaphases per animal were socred for structural chromosome aberrations using zeiss light microscopes with phase optics.
Morphological observations were scored as follows:
Gap - achromatic region in chromatid(s) not greater than the width of teh chromatid.
Break - achromatic region in chromatid(s) greater than the width of a chromatid or a discontinuity with displacement.
Exchange - aberrations arising from an exchange between one or two chromatids. These may be chromosome or chromatid interchanges. Only asymmetrical or chromatid exchanges will normally be recognised.
Multiple aberration - cells with more than 5 aberrations, gaps excluded.
Specific aberration - atypic chromosomes and pulverised metaphases were scored as specific aberrations.
The position of each aberrant metaphase was recorded by the Vernier reading and photographs taken of each aberrant metaphase. The frequency of polyploid cells were based on scoring of 1000 mitoses per animal. The estimation of the mitotic index was based on scording 1000 cells per animal.
- Evaluation criteria:
- Statistical significance compared with control groups would indicate a positive response.
- Statistics:
- The percentage of structural aberrant metaphases per animal, number of mitotic cells per 1000 cells per animal and the number of polyploid cells per 1000 mitoses per animal were used as parameters for statistical analysis.
Regarding structural aberrations two evaluations were conducted; one in which cells carrying gaps and isogaps as the only aberration are included and one where such cells are excluded.
The evaluation was performed applying a non parametric test (i.e. a modification of the Mann-Whitney-Wilcoxon test for tied values. Testing was performed against the one-sided alternative.
As more than one group was compared with controls, the level of significance was modified by the Bonferroni correction according to the number of groups. The values of positive controls were treated in the same way.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
Chinese Hamsters were dosed at 100, 120, 150, 200 or 250 mg/kg. Mortality was observed at the three highest doses. The dose of 120 mg/kg showed clear toxic effects (dyspnea and diarrhoea). Consequently this dose was chosen as the highest dose in the main study.
RESULTS OF DEFINITIVE STUDY
Structural aberrations: No chromosamal damaging affect was observed.
Polyploid cells: No statistically signifcant increase of polyploid cells were observed.
Mitotic index: No treatment-related variation was observed.
Bodyweight: No treatment-related variation was observed.
Clinica signs: 15 mg/kg (one animal observed to be prone), 120 mg/kg (three animals showed dyspnea, two showed ptosis, one had diarrhoea and one animal showed titubation. Most of the hamsters showed bluish urine.
Mortality: One animal died in each dose group.
Positive control: For the positive control, a statistically significant increase of aberrant metaphases for both evaluations (gaps included and excluded) was found.
Evidence of exposure: Clear evidence of systemic exposure and absorption of the test substance was apparent based on the observed clinical signs and mortality. Based on this obvious exposure it is very likely that the bone marrow was exposed to the test substance allowing for a full assessment of the clastogenic potential of the test substance.
The mean percentage of aberrant metaphases found 24 hours after treatment (gaps included) was 1.6% (negative control), 1.4% (15 mg/kg), 1.2% (40 mg/kg) and 1.3% (120 mg/kg). For the 120 mg/kg group the values were 2.0 and 1.3% at 6 and 48 hours respectively.
The corresponding values (gaps exlcuded) were 1.2, 1.0, 0.9 and 1.2% for the 24 hour groups and 1.7 and 1.1% for the 6 and 48 hour groups.
In the positive control the values were 6.1% (gaps included) and 5.9% (gaps excluded).
Any other information on results incl. tables
Aberrations per 100 cells (mean values)
Dose (mg/kg) |
Time (hours) |
Gaps |
Iso-gaps |
Breaks |
Iso-breaks |
Exchanges |
Multiple aberr. |
Specific aberr. |
Total aberr. Incl. |
Total aberr. Excl. |
0 |
24 |
0.4 |
0 |
0.7 |
0. |
0 |
0 |
0 |
1.8 |
1.4 |
15 |
24 |
0.4 |
0 |
0.6 |
0.4 |
0 |
0 |
0 |
1.4 |
1.0 |
40 |
24 |
0.3 |
0 |
0.6 |
0.3 |
0 |
0 |
0 |
1.2 |
0.9 |
120 |
6 |
0.3 |
0 |
0.8 |
1.0 |
0 |
0 |
0 |
2.1 |
1.8 |
120 |
24 |
0.1 |
0 |
0.6 |
0.6 |
0 |
0 |
0 |
1.3 |
1.2 |
120 |
48 |
0.2 |
0 |
0.6 |
0.7 |
0 |
0 |
0 |
1.5 |
1.3 |
20 (EMD) |
24 |
0.2 |
0 |
3.5 |
2.1 |
1 |
0.5 |
0 |
7.3 |
7.1 |
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the study, no chromosome damaging effects were observed in the bone marrow metaphases of male and female Chinese hamsters after a single oral dose at 15, 40 or 120 mg/kg of the test substance.
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