Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 215-202-6 | CAS number: 1313-13-9
- 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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: The study was not performed under GLP conditions, and the report contains unexplained inconsistencies. It is therefore not possible to ascertain the relibaility of the findings.
Data source
Reference
- Reference Type:
- publication
- Title:
- Short-term oral administration of several manganese compounds in mice: physiological and behavioural alterations caused by different forms of manganese
- Author:
- Komura J and Sakamoto M
- Year:
- 1 991
- Bibliographic source:
- Bulletin of Environmental, Contamination and Toxicology, 46:921-928
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Mice were exposed to MnO2 in their diet for 100 days and compared to controls fed on a diet containing 130 mg Mn/kg. Thirty days into the exposure period, mice were tested for spontaneous motor activity. Mice were decapitated 24 hours after their last feed. Blood samples were collected and analysed. Furthermore, tissues were removed, weighed and analysed for Mn content.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Manganese dioxide
- EC Number:
- 215-202-6
- EC Name:
- Manganese dioxide
- Cas Number:
- 1313-13-9
- Molecular formula:
- MnO2
- IUPAC Name:
- dioxomanganese
- Details on test material:
- - Molecular formula: MnO2
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: ddY
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: 28.2 ± 0.7 g
- Diet: ad libitum
- Water: ad libitum
Administration / exposure
- Route of administration:
- oral: feed
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 100 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2 g Mn / kg
Basis:
nominal in diet
- No. of animals per sex per dose:
- 8 males per dose group.
- Control animals:
- other: Standard laboratory mouse chow containing 130 mg Mn/kg
- Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule: Daily
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination
- How many animals: all animals
- Parameters checked included: red blood cell count, white blood cell count, haemoglobin and haematocrit
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: the mice were tested for spontaneous motor activity after an interval of 30 days. Activity was measured using an ANIMEX Activity Meter. Two mice were placed in a plastic cage at night, and after 10 minutes of acclimatisation, their activity was measured for 30 minutes. - Sacrifice and pathology:
- Mice were decapitated at 24 hours after their last feed.
Tissue samples were removed, weighed, and stored at -20°C until analysis. Hair was rinsed with ethyl alcohol and washed withsodium lauryl sulphate, and then dried. Tissues were digested by the wet ashing method and the resulting solutions were analysed for Mn content by atomic absorption spectroscopy with a flame atomizer.
Tissues sampled included: liver, kidney, pancreas, prostate gland, spleen, brain, hair, bone and muscle. - Statistics:
- Data were statistically analysed using Student's t-test and analysis of variance.
Results and discussion
Results of examinations
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- See "Details on results" for information
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- See "Details on results" for information
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- (Mn content of various tissues)
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- BODY WEIGHT AND WEIGHT GAIN: MnO2 did not cause any effect on weight change compared to the controls.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Food consumption was similar to controls. The mean daily food consumption was 3.6 ± 0.9 g in the control group and 3.8 ± 0.7 g in the MnO2 group.
HAEMATOLOGY: White blood cell count was significantly lower than the control
NEUROBEHAVIOUR: No locomotor differences were seen compared to the control
GROSS PATHOLOGY: manganese content in tissues was significantly greater than controls in the liver, kidney, spleen, hair, bone and muscle
Effect levels
- Dose descriptor:
- NOAEL
- Sex:
- male
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Manganese concentration in various tissues are shown below. Values represent the mean +/- SD for 8 mice
Organ | Control | MnO2 |
Liver | 2.80±0.39 | 4.30±0.58c) |
Kidney | 2.84±0.23 | 3.70±0.37c) |
Pancreas | 2.04±0.23 | 2.75±1.01 |
Prostate gland | 1.18±0.21 | 1.60±0.40 |
Spleen | 0.40±0.06 | 0.85±0.30 b) |
Brain | 0.97±0.25 | 1.45±0.50 |
Hair | 2.98±0.42 | 4.13±0.85 b) |
Bone | 1.66±0.32 | 2.75±0.25c) |
Muscle | 0.37±0.04 | 0.63±0.10c) |
b) p < 0.05
c) p < 0.01 (Student’s t-test), i.e. statistically significantly different to control
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Intake rate decreased within the first month but then became constant in all groups.
Applicant's summary and conclusion
- Conclusions:
- Due to inconsistencies in the study, the certainty of the results for MnO2 are bought into question, and as such it is difficult to make solid conclusions. Given the low bioavailability of MnO2 (actually, the lowest for all manganese substances tested, see Anderson K, IUCLID section 7.12) and its insoluble nature ( 0.073 mg/L, See IUCLID section 4. 8 ) the raised Mn concentrations relative to the control could also be seen as unusual.
- Executive summary:
The repeated dose toxicity of manganese dioxide was investigated in a study in which mice were exposed to MnO2 in the diet for 100 days and compared to controls fed on a diet containing 130 mg Mn/kg. The mice receiving MnO2 were fed an additional Mn dose of approximately 200 mg Mn/kg bw, daily. Thirty days into the exposure period, mice were tested for spontaneous motor activity. Mice were decapitated 24 hours after their last feed. Blood samples were collected and analysed. Furthermore, tissues were removed, weighed and analysed for Mn content.
There was no effect on food intake or body weight development between the controls and the group fed MnO2 during the course of the study. White blood cells (40.6 ± 9.9 x 10^2/mm³) ashowed a slight decrease compared to controls (59.3 ± 18.0 x 10^2/mm³); the difference was statistically significant (p < 0.05). Mn concentrations in the liver, kidney, spleen, hair, bone, and muscle were significantly increased in the MnO2 group compared to the controls. In the control group, motor activity increased from days 15-45, thereafter remaining constant. The MnO2 group showed significantly less activity than the control group.
Due to inconsistencies in the study, the certainty of the results for MnO2 are bought into question, and as such it is difficult to make solid conclusions; the findings from this study are therefore diregarded.
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.

Route: .live1