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EC number: 214-230-6 | CAS number: 1115-70-4
- 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
- Study period:
- 1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- other: Mouse MN test OECD 474
Test material
- Reference substance name:
- Metformin hydrochloride
- EC Number:
- 214-230-6
- EC Name:
- Metformin hydrochloride
- Cas Number:
- 1115-70-4
- Molecular formula:
- C4H11N5.ClH
- IUPAC Name:
- N,N-dimethylimidodicarbonimidic diamide hydrochloride
- Test material form:
- solid: bulk
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on species / strain selection:
- Strain: SPF outbred CD1
Source: Charles River UK
Weight: 22-24 g
Age: 35 d - Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 35 d
- Weight at study initiation: 22-24 g
- Assigned to test groups randomly: yes, under following basis: separated by sex
- Fasting period before study: overnight prior to and for 2 hours after dosing
- Housing: grouped separated by sex plastic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum) ad libitum:
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): n.d.
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): 12/12 h
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Water
- Duration of treatment / exposure:
- single dose
- Frequency of treatment:
- 1
- Post exposure period:
- 24, 48, 72 h after dosing
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 000 mg/kg bw/day
- Dose / conc.:
- 0 mg/kg bw/day
- No. of animals per sex per dose:
- Neg. Control: 15 f, 15 m
2000 mg/kg Metformin HCl: 20 f, 20 m
Pos. Control: 5 f, 5 m - Control animals:
- yes
- Positive control(s):
- 12 mg/kg bw Mitomycin C
Examinations
- Tissues and cell types examined:
- Bone marrow
- Details of tissue and slide preparation:
- - direct bone marrow smears prepared on slides
- Methanol fixation (10 min)
- Giemsa staining - Evaluation criteria:
- MN incidence per 1000 PCEs per animal
- Statistics:
- Standard statistical methods have been applied for data processing.
Results and discussion
Test results
- Key result
- 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
Summary of results - group totals/means for the entire experiment and results of the statistical analysis
Samplng Time |
Treatment |
Dose / (mg/kg) |
Ratio p/n (mean) § |
Incidence mnp (mean) § |
Incidence mnn (total) |
24 hour |
Vehicle control |
- |
0.847 |
0.2 |
0.2 |
Metformin HCl |
2000 |
1.059ns |
0.9ns | 0.2 |
|
Mitomycin C |
12 |
0.759ns | 40.3 *** | 0.4 |
|
48 hour |
Vehicle control | - |
1.146 |
1.0 |
0.2 |
Metformin HCl | 2000 |
0.936ns | 0.6ns | 0.4 |
|
72 hour |
Vehicle control | - |
1.228 |
0.8 |
0.6 |
Metformin HCl | 2000 |
1.165ns | 0.2ns | 0.4 |
p/n Ratio of polychromatic to normocbromatic erythrocytes
mnp Number of micronucleaied cells observed per 1000 polycbromatic
erythrocytes
mnn Number of micronucleated cells observed per 1000 normochromatic
erythrocytes
§ Results of statistical analysis using Wilcoxon's sum of ranks test
(one-sided):
ns P > 0.05
*** P < 0.001
Applicant's summary and conclusion
- Conclusions:
- It is concluded that Metformin hydrochloride has not shown any evidence of causing chromosome damage in this in vivo test.
- Executive summary:
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 474. It is concluded that Metformin hydrochloride has not shown any evidence of causing chromosome damage in this in vivo test.
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