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EC number: 242-599-3 | CAS number: 18820-29-6
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted to sound scientific principles with a suficient level of detail to assess the reliability of the relevant results. There was a sufficient number of plasma time-points to enable TK calculations to be made. The materials and methods only give details of male rats, yet results are quoted for female rats for MMT.
Data source
Reference
- Reference Type:
- publication
- Title:
- Comparative toxicokinetics of manganese chloride and methylcyclopentadienyl manganese tricarbonyl (MMT) in Sprague-Dawley rats.
- Author:
- Zheng W, Kim H and Zhao Q
- Year:
- 2 000
- Bibliographic source:
- Toxicol Sci 54:295-301
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- Deviations:
- yes
- Remarks:
- One dose level used rather than the recommended two. For MnCl2, only male rats are used.
- Principles of method if other than guideline:
- The toxicokinetics of manganese (Mn) was investigated in male and female rats either following a single intravenous (iv) or oral dose of MnCl2 (6.0 mg Mn/kg), or following a single oral dose of methylcyclopentadienyl manganese tricarbonyl (MMT) (20 mg MMT/kg or 5.6 mg Mn/kg). The plasma concentrations of manganese were quantified by atomic absorption spectrophotometry (AAS).
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Manganese dichloride
- EC Number:
- 231-869-6
- EC Name:
- Manganese dichloride
- Cas Number:
- 7773-01-5
- Molecular formula:
- Cl2Mn
- IUPAC Name:
- manganese(2+) dichloride
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Inc Indianapolis IN.
- Age at study initiation: 2 months
- Weight at study initiation: 210-230g
- Fasting period before study: 12 hours before oral study
- Diet: Ad libitum, Teklad 4% Mouse-Rat Diet
- Water: Ad libitum, Tap water
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature controlled (no temperature stated)
- Photoperiod (hrs dark / hrs light): 12:12h light/dark
Administration / exposure
- Route of administration:
- other: oral and iv for MnCl2 and oral only for MMT
- Vehicle:
- other: Sterile saline for MnCl2 and corn oil for MMT
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: MnCl2 dissolved in sterile saline for both iv and oral administration both dosed at 6.0mg Mn/kg (1.0mL/kg). MMT was dissolved in corn oil and dosed at 20mg/kg (3.3mL/kg in volume) equivalent to 5.6mg Mn/kg.
- Duration and frequency of treatment / exposure:
- Single dose for each test.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
MnCl2 dissolved in sterile saline for both iv and oral administration both dosed at 6.0mg Mn/kg (1.0mL/kg). MMT was dissolved in corn oil and dosed at 20mg/kg (3.3mL/kg in volume) equivalent to 5.6mg Mn/kg.
For the iv dosing study, MnCl2 was injected via the tail vein at a dose of 6.0 mg Mn/kg (1.0 mL/kg) over approximately 5 seconds. For the oral dosing study, MnCl2 was administered by a single gavage at the same dose level. MMT was also dosed by a single oral gavage to rats.
- Control animals:
- not specified
- Details on study design:
- For the oral dose MnCl2 was administered by a single gavage at 6.0mg Mn/kg as it was known to be associated with a significant reduction of succinic dehydrogenase and aconitase in rat brain.
- Details on dosing and sampling:
- MnCl2
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Blood plasma (0.3-0.5mL)
- Time and frequency of sampling: 0, 0.05, 0.17, 0.33, 0.5, 1, 2, 4, 8, and 12 h
MMT
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Blood plasma (0.3-0.5mL)
- Time and frequency of sampling: 0, 0.17, 0.5, 1, 2, 4, 8, 12, 24, 48, 120, 168, 288, 384, and 456 h - Statistics:
- Statistical analysis for comparison of two means was performed usinf one-way ANOVA. In all cases, a probility level of p < 0.05 was considered as the criterion of significance.
Results and discussion
Toxicokinetic / pharmacokinetic studies
Toxicokinetic parametersopen allclose all
- Toxicokinetic parameters:
- Tmax: MMT male: 5.50±4.43h
- Toxicokinetic parameters:
- Tmax: MMT female: 10.0±2.31h
- Toxicokinetic parameters:
- Tmax: MMT combined: 7.75±4.06h
- Toxicokinetic parameters:
- Cmax: MMT male: 0.79±0.36µg/mL
- Toxicokinetic parameters:
- Cmax: MMT female: 1.07±0.46µg/mL
- Toxicokinetic parameters:
- Cmax: MMT combined: 0.93±0.41µg/mL
- Toxicokinetic parameters:
- AUC: MMT male: 51.8±10.9mM·h
- Toxicokinetic parameters:
- AUC: MMT female: 93.1±30.7mM·h
- Toxicokinetic parameters:
- AUC: MMT combined: 72.5±30.7mM·h
- Toxicokinetic parameters:
- Tmax: Oral dose MnCl2: 0.25±0.21 h
- Toxicokinetic parameters:
- Cmax: Oral dose MnCl2: 0.30±0.11µg/mL
- Toxicokinetic parameters:
- AUC: Oral dose: MnCl2 1.95±0.51 mM·h
- Toxicokinetic parameters:
- AUC: iv dose MnCl2: 14.8±3.60 mM·h
Any other information on results incl. tables
Upon iv administration of MnCl2, manganese rapidly disappeared from blood with a terminal elimination t1/2 of 1.83 h and CL8 of 0.43 L/h/kg. The plasma concentration-time profiles of manganese could be described by C = 41.9e(-424t) + 2.1e(-0.44t). Following oral administration of MnCl2, manganese rapidly entered the systemic circulation (Tmax = 0.25 h). The absolute oral bioavailability was about 13%. Oral dose of MMT resulted in a delayed Tmax (7.6 h), elevated Cmax (0.93 microg/mL), and prolonged terminal t1/2 (55.1 h). The rats receiving MMT had an apparent clearance (CL/F = 0.09 L/h x kg) about 37-fold less than did those who were dosed with MnCl2. Accordingly, the area under the plasma concentration-time curves (AUC) of manganese in MMT-treated rats was about 37-fold greater than that in MnCl2-treated rats. A gender-dependent difference in toxicokinetic profiles of plasma manganese was also observed. Female rats displayed a greater AUC than that of male rats. Although the apparent volume of distribution of manganese was similar in both sexes, the apparent clearance in males was about twice that observed in females.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: low bioaccumulation potential based on study results
The results indicated that after oral administration, the MMT-derived manganese displayed higher and more prolonged plasma concentration-time profiles than MnCl2-derived manganese. Thus, MMT-derived manganese appeared likely to accumulate in the body following repeated exposure.
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