Registration Dossier
Registration Dossier
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EC number: 231-869-6 | CAS number: 7773-01-5
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:
- Although a brief communication, this is an important mechanistic study with results that suggest that iron homeostasis may play an important role in the regulation of manganese transport across the blood-brain barrier (BBB). Restrictions - no claims that the study had been conducted and reported according to internationally accepted guidelines or in compliance with the principles of GLP.
Data source
Reference
- Reference Type:
- publication
- Title:
- Manganese transport across the blood-brain barrier: relationship to iron homeostasis
- Author:
- Aschner M and Aschner JL
- Year:
- 1 990
- Bibliographic source:
- Brain Res Bull 24:857-860
Materials and methods
- Objective of study:
- distribution
- Principles of method if other than guideline:
- The binding characteristics of manganese (Mn) to transferrin (Tf) were examined on G-75 Sephadex gel columns and in vivo transport of Mn across the BBB was measured by clinigamma 1272 spectrometer.
- 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:
- Long-Evans
- Sex:
- female
Administration / exposure
- Route of administration:
- infusion
- Vehicle:
- physiological saline
- Duration and frequency of treatment / exposure:
- continuous infusion for 6hrs (1mL/hr) with ferric-hydroxide dextran complex
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2.2 * 10-6 M MnCl2 - Mn binding to transferrin
0.55 * 10-6 M MnCl2 - In vivo transport of Mn across the BBB
- No. of animals per sex per dose / concentration:
- 6 rats per dose
- Control animals:
- yes
Results and discussion
Any other information on results incl. tables
When 54MnCl2 was combined with Tf and immediately fractioned on a Sephadex column, 49% of 54Mn was bound to Tf. Amount bound was dependent on incubation periods and increased in a time dependent manner. In vivo 6 hr IV of ferric-hydroxide dextran complex significantly inhibited 54Mn brain uptake as compared to its uptake in iron-free dextran-treated rats.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: Bioaccumulation potential cannot be judged based on study results
Results suggest that Fe homeostasis may play an important role in the regulation of Mn transport across the blood-brain barrier.
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