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EC number: 202-086-7 | CAS number: 91-64-5
- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 984
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Coumarin
- EC Number:
- 202-086-7
- EC Name:
- Coumarin
- Cas Number:
- 91-64-5
- Molecular formula:
- C9H6O2
- IUPAC Name:
- 2H-chromen-2-one
- Test material form:
- solid: crystalline
- Details on test material:
- -Name of test material: Coumarin
-Substance type: Pure substance
-Physical state: White crystalline powder
-Analytical purity: >99%
-Lot/batch No.: Batch no. CA 83 320-01
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Species and strain: CD1 mouse from CHARLES RIVER FRANCE.
Age: 7 weeks on arrival
Number: 60 males and 60 females received for this study that requires 50 males and 50 females, the distribution of animals in the various groups is given in paragraph 2.3
-Acclimation: The acclimation period is 7 days.
Accommodation and environmental control:
Environmental conditions:
-Temperature: 22℃
- Humidity: 55%
- Lighting control: 12 hours light and 12 hours dark per 24 hours.
The mice were housed at a maximum of five same-sex cage in stainless steel cages of 24*25*13 cm.
Administration / exposure
- Route of administration:
- oral: unspecified
- Details on exposure:
- Coumarin is administered once or twice orally in a volume of 25mg/kg
- Duration of treatment / exposure:
- one or two administrations spaced 24 hours.
- Frequency of treatment:
- once or twice
- Post exposure period:
- 30 hours after a single treatment and 48 hours after the first of two 24-hour spaces treatments.
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
35mg/kg bw
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
70 mg/kg bw
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
105mg/kg bw
Basis:
nominal in diet
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Mice were treated once or twice withthe cyclophosphamide at a dose of 60mg/kg ip in a volume.
Examinations
- Tissues and cell types examined:
- Bone marrow cells.; the incidence of micronucleated polychromatic erythrocyts.
- Details of tissue and slide preparation:
- Details of slide preparation
Sacrifice:
The mouses were sacrificed by CO2 inhalation. The mice received an administration were sacrificed 30 hours after it. The other mice received two administration were sacrificed 48 hours after the first administration.
A femur of each mouse is removed by rotary section around the joint. The muscles are carefully peeled form the bone. The bone marrow cells
were transferred to a tube containing 1ml fetal bovine serum. The tubes are placed in a centrifuge for 5min at 1000Rev/min.
Most of the supernatant shall be eliminated. Each pellet was resuspended in one or two drops of supernatnt puris spead over two slides. The slides were fixed in methanol, stained with May-Gruenwald-Giemsa.
micronuclei rate of Polychromatic erythrocytes in bone marrow: 1000 erythrocytes/mouse and thus 10000 erythorcyts/group count the corresponding number of micronuclei.
Each mouse has two corresponding slides. With immersion, at least 500 polychromatic erythrocytes/slides (ie 1000 erythrocytes/mouse) and thus 10000 erythrocytes/group counts the corresponding number of micronuclei.
To evaluate bone marrow cytotoxicity, 100 normochromatic erythrocytes and the corresponding number of polychromatic erythrocytes were counted per slides. - Evaluation criteria:
- The comparison of different groups is carried out by the test kasten-baum and Bowman. Counting of 10,000 erythrocytes per group allows to detect a significant increase of approximately 2 times the spontaneous rate of polychromatic erythrocytes with micronuclei.
- Statistics:
- Statistical analysis of cytotoxicity is effected using analysis of variance followed by comparison of treated groups with control groups.
In the tables, the degree of significance is indicated by the following legends
* Significant increase for P less than or equal to 0.05
** Significant increase for P less than or equal to 0.01
**** Significant increase for P less than or equal to 0.001
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
TABLEAU N° 1 | ||||||
COUMARINE-Erythrocytes poìychromatophiles avec micronoyaux | ||||||
Valeurs moyennes (en pour mille) | ||||||
Temps (heures) | S.G.10 % (b) | Coumarine | Cyclophos-phamide | |||
0 | 35 mg/kg | 70 mg/kg | 105 mg/kg | 60 mg/kg | ||
30 | total (a) | 11 | 23 | 32* | 29* | 534 |
moy. | 1, 1 | 2, 3 | 3, 2 | 2, 9 | 53, 4 *** | |
48 | total (a) | 10 | 10 | 18 | 15 | 590 |
moy. | 1, 0 | 1, 0 | 1, 8 | 1, 5 | 59, 0 *** | |
(a) Sur 10 000 érythrocytes poìychromatophile. | ||||||
(b) Solution aqueuse à 10% de gomme arabique. |
TABLEAU N° 2 | |||||
COUMARINE-Etude de la cytotoxicité | |||||
Valeurs moyennes: [∑xi/(200 EN)]/10 (1) | |||||
Temps (heures) | S.G.10 % (b) | Coumarine | Cyclophos-phamide | ||
0 | 35 mg/kg | 70 mg/kg | 105 mg/kg | 60 mg/kg | |
30 | 1, 27 | 1, 55 | 1, 20 | 1, 50 | 0, 58 *** |
48 | 1, 59 | 1, 74 | 1, 53 | 1, 61 | 0, 25 *** |
(a) Solution aqueuse à 10% de gomme arabique. |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
See Excetutive summary
00000000000000000 - Executive summary:
Introduction:
In mice, the possble clastogenic activity of coumarin adminstrated in oral, was studied in the micronulceus test.
They cyclophophamide was studied in parallel as positive control.
Results:
At time 30 hours, there was a slight significant increase of polychromatic erythrocytes with micronuclei. According to our criteria of evalaution of the clastogenic, increased micronuclei the 70mg/kg dose considered as doubtful. However, there's no clear dose effect at time 30hours.
For cons, the adminstration intraperitoneal dose of cyclophosphamide 60mg/kg causes both studied a net clastogenic (+++) and strong cytotoxic marrow.
Conclusion:
Coumarin, administered orally at doses 105mg/kg, presents a doubtful clastogenic effect in the micronucleus test in mice at time 30hours.
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