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EC number: 231-104-6 | CAS number: 7439-95-4
- 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
Neurotoxicity
Administrative data
Description of key information
There are conclusive but not suffcient data for the classification of substance Magnesium (CAS No. 7439-95-4) with regard to Neurotoxicity.
Key value for chemical safety assessment
Effect on neurotoxicity: via oral route
Link to relevant study records
- Endpoint:
- neurotoxicity: short-term oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Materials and methods well described; results presented properly in the text and tables.
- Qualifier:
- according to guideline
- Guideline:
- other: All experiments were carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC)
- Deviations:
- not applicable
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: OF1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Centre d'Elevage Depre, Doulcharel, France
- Weight at study initiation: 20-25g
- Fasting period before study: 12 hours
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Photoperiod: 12 hours dark/light cycle - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Drugs and vehicle were administered per os (PO) in a constant volume of 10 ml/kg body weight.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- no data
- Frequency of treatment:
- single
- Remarks:
- Doses / Concentrations:
100-300 mg/kg body weight
Basis:
nominal conc. - No. of animals per sex per dose:
- groups of 10-15 animals
- Control animals:
- yes
- Details on study design:
- Examination of the protective effect of magnesium salts against seizures induced by NMDA, pentylenetetrazol, bicuculline and strychnine in naive animals. Magnesium salts were given 30 minutes before administration of convulsant. Immediately after administration of the convulsant drug, animals were individually placed in plastic cages. A full seizure was recorded when clonic movements of the limbs were observed, accompanied by loss of posture. The presence or absence of convulsions, time to the first convulsive period, and lethality during the observation period were noted.
- Observations and clinical examinations performed and frequency:
- Determination of plasma magnesium level: Blood samples were collected from mice at different times after oral administration of magnesium salts. Plasma aliquots were stored at -20°C until analysis. Magnesium level was determined.
- Specific biochemical examinations:
- no data
- Neurobehavioural examinations performed and frequency:
- Forced swimming test: The swimming test was performed in glass cylinders (18 cm in diameter and 40 cm high) containing 10 cm deep water at 25°C. The total immobility time was assessed throughout a 6-minute observation period. The test was started 1 hour after drug administration.
Locomotor activity: Locomotor activity was measured in photoresistor actometers in which the animals were placed individually 1 hour after drug administration. Activity counts were recorded for 15 minutes.
Motor coordination: 1 hour after administration of the test compound, animals were placed for 180 seconds on a rotarod apparatus revolving at 16 rpm. The frequency with which mice fell from the rod during this period was scored. - Sacrifice and (histo)pathology:
- no data
- Other examinations:
- no data
- Positive control:
- no data
- Statistics:
- Student's t-test
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Clinical biochemistry findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Other effects:
- not examined
- Description (incidence and severity):
- Migrated information from 'Further observations for developmental neurotoxicity study'
Details on results (for developmental neurotoxicity):no (migrated information) - Details on results:
- A rapid increase in plasma Mg2+ level was observed as early as 30 minutes after treatment. This hypermagnesia persisted over the next two hours and declined after 6 hours. No lethal effect was observed.
A single oral dose of Mg revealed a significant dose-dependent antagonistic effect on the latency of NMDA-induced convulsions. An anticonvulsive effect was also observed with strychnine- induced convulsions (but not with bicuculine-, picrotoxin and pentylenetetrazole). In the forced swim test, Mg reduced the immobility time indicating anti-depressant-like activity. Administration of Mg strongly potentiates yohimbine lethality and did not prevent reserppine-induced hypothermia. - Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: oral administration of magnesium to normal mice can antagonise NMDA-mediated responses and lead to anti-depressant-like effects.
- Remarks on result:
- other:
- Conclusions:
- In summary, oral administration of magnesium to normal mice can antagonise NMDA-mediated responses and lead to anti-depressant-like effects.
- Executive summary:
The ion channel of the N-methyl-D-aspartate (NMDA) receptor complex is subject to a voltage-dependent regulation by Mg2+ cations. Under physiological conditions, this channel is supposed to be blocked by a high concentration of magnesium in extracellular fluids. A single dose of magnesium organic salts (i.e., aspartate, pyroglutamate, and lactate) given orally to normal mice rapidly increases the plasma Mg2+ level and reveals a significant dose-dependent antagonist effect of magnesium on the latency of NMDA-induced convulsions; this effect is similar to that seen after administration of the dizocilpine (MK-801) channel blocker. An anticonvulsant effect of Mg2+ treatment is also observed with strychnine-induced convulsions but not with bicuculline-, picrotoxin-, or pentylenetetrazol-induced convulsions. In the forced swimming test, Mg2+ salts reduce the immobility time in a way similar to imipramine and thus resemble the antidepressant-like activity of MK-801. This activity is masked at high doses of magnesium by a myorelaxant effect that is comparable to MK-801-induced ataxia. Potentiation of yohimbine fatal toxicity is another test commonly used to evaluate putative antidepressant drugs. Administration of Mg2+ salts, like administration of imipramine strongly potentiates yohimbine lethality in contrast to MK-801, which is only poorly active in this test. Neither Mg2+ nor MK-801 treatment can prevent reserpine-induced hypothermia. These data demonstrate that oral administration of magnesium to normal animals can antagonize NMDA-mediated responses and lead to antidepressant-like effects that are comparable to those of MK-801. This important regulatory role of Mg2+ in the central nervous system needs further investigation to evaluate the potential therapeutic advantages of magnesium supplementation in psychiatric disorders.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- mouse
Effect on neurotoxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 13 mg/m³
- Study duration:
- subchronic
- Species:
- mouse
Effect on neurotoxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 2.4 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- mouse
Additional information
oral exposure
oral administration of magnesium to normal mice can antagonise NMDA-mediated responses and lead to anti-depressant-like effects.
NOAEL=300 mg/kg bw day
dermal exposure
For dermal exposure we taken that:
-the average weight of mice is 80 g (60 -100 g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg
corrected dermal NOAEL= oral NOAEL
300 mg/kg bw/dx 0.008 kg =
NOAECmouse 2.4 mg/kg bw/day
Inhalation exposure:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the mouse (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL mouse 300 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/mouse
NOAECmouse = 13 mg/m3
Justification for selection of effect on neurotoxicity via inhalation route endpoint:
Inhalation exposure:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the mouse (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL mose 300 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECmouse = 13 mg/m3
Justification for selection of effect on neurotoxicity via dermal route endpoint:
dermal exposure
For dermal exposure we taken that:
-the average weight of mice is 80 g (60 -100 g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg
corrected dermal NOAEL= oral NOAEL
300 mg/kg bw/dx 0.008 kg =
NOAECmouse 2.4 mg/kg bw/day
Justification for classification or non-classification
There are conclusive but not suffcient data for the classification of substance Magnesium (CAS No. 7439 -95 -4) with regard to Neurotoxicity.
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