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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
Endpoint summary
Administrative data
Description of key information
The acute toxicity of Metformin hydrochlorid was studied in various species via the oral route of administration. The LD50 values varied between 375 mg/kg bw in dogs and 2400 mg/kg bw in mice. For rats an LD50 (m/f) of 1770 mg/kg bw is reported.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1984-04-03 to 1984-06-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- Metformin Hydrochloride
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River
- Age at study initiation: young
- Weight at study initiation: 288.2g (males) and 216.4g (females)
- Fasting period before study: overnight
- Housing: single in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 12-15 / hour
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1984-04-04 To: day 1984-04-24 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 25 %
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: dose range finding - Doses:
- 1000, 1320, 1730, 2280, 3000 mg/kg bw
- No. of animals per sex per dose:
- 5 animals/sex/dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed:
clinical signs: frequently during the day of dosing and then daily thereafter for 14 days
body weight: prior to dosing and after 7 and 14 days
gross necropsy to all animals dying during the 14-day observation period - Statistics:
- Probit analysis was used for LD50 calculation.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 1 770 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- > 1 510 - < 2 100
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 1 600 mg/kg bw
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Mortality was observed starting at the lowest dose of 1000 mg/kg bw
- Clinical signs:
- other: decreased activity, ataxia, tremors, diarhea, salivation
- Gross pathology:
- no test item related leasions were reported
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- In an oral toxicity study in rats equivalent to OECD 401, the acute oral LD50 of the test article for both sexes combined was calculated to be 1.77 g/kg body weight with a 95% confidence interval of 1.51 to 2.10 g/kg.
- Executive summary:
The test material was evaluated for acute oral toxicity in male and female Sprague-Dawley rats. The substance was orally administered (gavage) dissolved in water as the vehicle to animals (5 per sex per group) at dose levels of 1000, 1320, 1730, 2280 and 3000 mg/kg bw. After administration, the rats were observed for mortality and clinical signs up to 14 days after treatment. All animals were weighed before treatment (day1) and therafter on day 8 and day 15. All animals dying during the study were subjected to a gross necropsy.
Mortalities were dose dependent and observed starting at the lowest dose of 1000 mg/kg bw. All deaths occurred within 24 hours following dose administration. Decreased activity, ataxia, tremors, diarrhea, salivation were noted as clinical signs.
Under the conditions of this study, the acute oral LD50 of the test article in rats in both sexes combined was calculated to be 1770 mg/kg bw (1,77 g/kg body weight) with a 95% confidence interval of 1,51 to 2,10 g/kg.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 770 mg/kg bw
- Quality of whole database:
- For this endpoint high quality data (GLP + OECD TG compliant) are available for different species.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
- Justification for type of information:
- cf. results of granulometry study, showing particles clearly exceeding a size 10 µm (296 µm (50%), of 80 µm (10%) and of 660 µm (90%)), thus, no repirable fraction was detected. Therefore inhalative exposure is highly unlikely.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
- Justification for type of information:
- The octanol water distribution coefficient (logP) provides a first estimate on the skin penetration and thus the dermal exposure of a given chemical. The logP is a constant defined as the ratio of equilibrium concentrations of a chemical dissolved in a two-phase immiscible system consisting of water and octanol. A log P of 0 describes a compound that is equally soluble in organic and aqueous media. A logP of 1 indicates a 10:1 solubility ratio of the chemical in the organic:aqueous phase. The solubility ratio of a chemical with a log P value of −1 is 1:10 in the organic:aqueous phase.
Consequently, chemicals with negative log P values are more soluble in aqueous media than in organic solvents and will partition to the aqueous instead of the lipophilic phase. Metformin HCl has a logP at -3.5, i.e. clearly below 0.
The stratum corneum consists of approximately 40% water (Warner et al., 1988). Therefore, octanol serves as a simplified model of the stratum corneum. For log P, a threshold of zero determines the percutaneous penetration behaviour. The logP of Metformin is clearly below this threshold indicating that a dermal absorption can be excluded. Therefore no systemic exposure can be assumed after dermal administraion and thus there is no need for further studies on acute dermal toxicity.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
The acute toxicity of Metformin hydrochlorid was studied in various species via the oral route of administration. The LD50 varies between 375 mg/kg bw in dogs and 2400 mg/kg bw in mice. For rats an LD50 (m/f) of 1770 mg/kg bw is reported. In monkeys the LD50 ammounts to 400 mg/kg bw.
Comparing different species, the LD50 values show significant variations. However, considering allometric scaling to account for species differences yields an acute toxicity range between 300 and 2000 mg/kg bw.
Justification for selection of acute toxicity – oral endpoint
This study was performed according to GLP using the standard species
(rat) and the methods applied are fully compliant with OECD TG 401.
Justification for classification or non-classification
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.