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EC number: 235-166-5 | CAS number: 12108-13-3
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not mentioned
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study performed similar to OECD 474 with minor restrictions. Sufficient informarion on methods and results for assessment.
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- No detailed information on the test material
- GLP compliance:
- not specified
- Remarks:
- Test conducted at the laboratories of Health and Welfare Canada
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Tricarbonyl(methylcyclopentadienyl)manganese
- EC Number:
- 235-166-5
- EC Name:
- Tricarbonyl(methylcyclopentadienyl)manganese
- Cas Number:
- 12108-13-3
- Molecular formula:
- C9H7MnO3
- IUPAC Name:
- tricarbonyl(methyl-η5-cyclopentadienyl)manganese
- Details on test material:
- - Name of test material (as cited in study report): mmt
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- C57BL
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9 weeks old (Three daily treatment protocol) and 47-59 days old (single treatment protocol)
- Weight at study initiation: No data
- Assigned to test groups randomly: yes
- Fasting period before study: No
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
No data
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: USP grade olive oil (Life Brand)
- Justification for choice of solvent/vehicle: mmt is poorly soluble in water
-Amount injected: 0.1 ml/10 g body weight - Details on exposure:
- The exposure was done through intraperitoneal injection.
- Duration of treatment / exposure:
- Trial 1 - Three days
Trial 2 - Single dose (1 day) - Frequency of treatment:
- 1 single dosage per day.
- Post exposure period:
- Trial 1 - 24 hours
Trial 2 - Samples were collected 24 and 48 hours after exposure.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Trial 1 (3 days study) - 12.5, 25 and 50 mg/kg bw/day; Trial 2 (1 day study) - 50, 75 and 100 mg/kg bw/day.
Basis:
other: injected
- No. of animals per sex per dose:
- Trial 1 - 5 males and 5 females per dose
Trial 2 - 5 males and 5 females per dose - Control animals:
- yes
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): known inducer of chromosomal aberrations upon metabolic activation
- Route of administration: intraperitoneal
- Doses / concentrations:
Trial 1 (3 days treatment) - 45 mg/kg cyclophosphamide dissolved in phosphate buffered saline
Trial 2 (1 day treatment) - 25 mg/kg cyclosphosphamide in phosphate buffered saline
Examinations
- Tissues and cell types examined:
- Polychromatic (PE) (orange) and normochromatic (NE) (very pale green) erytrocytes.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
-Trial 1 (3 days treatment)- A preliminary range-finding study using 2 animals of each sex and the same treatment regimen to be used in the micronucleus test, indicated that doses above 50 mg/kg could cause animal deaths or distress.
-Trial 2 (1 day treatment) - In order to determine the Maximum Tolerable Dose (MTD) for single i.p. injections, 2 mice of each sex were injected with the test material and monitored for 48 hours for signs of toxicity. The dose was administered in a volume of 0.1 ml/10 g bw. It was concluded that single treatments at doses above 100 mg/kg were likely to kill some of the animals.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
- Trial 1 - 24 hours following last treatment
- Trial 2 - 24 and 48 hours following treatment
DETAILS OF SLIDE PREPARATION:
For both trial 1 and 2: Samples were collected 24 hours following the final treatment. Immediately following sacrifice by cervical dislocation, one femur was removed and flushed out using a 1 ml syringe fitted with a 20 gauge needle, with approximately 0.1 ml fetal calf serum containing EDTA (prepared by filling a purple-topped vacutainer with serum) into a depression dish. The cell suspension was mixed with the tip of a disposable transfer pipet, then a drop was transferred to each slide. The slides were allowed to air dry, then fixed in methanol for approximately 5 min.
METHOD OF ANALYSIS:
Slides were coded and score blind to avoid observer bias. For analysis, the slides were mounted under a #1 coverslip in Sorensen's buffer, pH 7.3. Cells were viewed under epi-fluorescence on a Nikon Optiphot microscope fitted with a 60x objective and using a Nikon type G filter block. The number of polychromatic (PE) (orange) and normochromatic (NE) (very pale green) erythrocytes were recorded for the first 1000 erythrocytes (i.e., PE+NE) had been counted. After the first 1000 erythrocytes had been counted, only PE were scored until a total of 2000 PE had been analysed. On slides were the ‰ (1 part in 1,000) MPE exceeded 20, only 1000 PEs were analysed. - Statistics:
- Data were analysed using the micronucleus assay data management and analysis system software developed under contact to the USEPA.
Results and discussion
Test resultsopen allclose all
- Sex:
- female
- Genotoxicity:
- negative
- Remarks:
- Trial 1, 3 days exposure
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Trial 1, 3 days exposure
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: a dose-range finding study was performed using 2 animals of each sex per each dose, indicated that doses above 50 mg/kg could cause animal death or distress
RESULTS OF DEFINITIVE STUDY
- Appropriateness of dose levels and route: yes, dose levels defined after a dose-range finding study
- Statistical evaluation: yes
Any other information on results incl. tables
Table 1 – summary of micronucleus induction by mmt (Trial 1, 3 day exposure)
Dose (mg/kg) |
Total MPCE |
Total PCE |
% MPCE |
SEM |
Pairwise Significance |
Total PCE |
Total PCE+NCE |
% PCE |
SEM |
Pairwise Significance |
Females |
||||||||||
0 |
38 |
10000 |
0.380 |
0.034 |
|
3800 |
5788 |
65.65 |
3.33 |
|
12.5 |
26 |
8842 |
0.294 |
0.124 |
0.844 |
3700 |
5311 |
69.67 |
5.26 |
0.755 |
25.0 |
34 |
10000 |
0.340 |
0.025 |
0.682 |
3920 |
5265 |
74.45 |
3.71 |
0.939 |
50.0 |
28 |
10000 |
0.280 |
0.078 |
0.891 |
3771 |
5209 |
72.39 |
2.20 |
0.879 |
CP |
219 |
5000 |
4.380 |
0.459 |
0.000 |
2500 |
5539 |
45.13 |
4.23 |
0.000 |
Trend for %MPCE: p=0.849 Trend for %PCE: p=0.440 |
||||||||||
Males |
||||||||||
0 |
42 |
10000 |
0.420 |
0.085 |
|
3400 |
5489 |
61.94 |
5.76 |
|
12.5 |
41 |
10000 |
0.410 |
0.086 |
0.544 |
4000 |
5343 |
74.86 |
2.51 |
0.987 |
25.0 |
29 |
10000 |
0.290 |
0.010 |
0.939 |
3800 |
5292 |
71.81 |
3.83 |
0.952 |
50.0 |
25 |
9177 |
0.272 |
0.058 |
0.958 |
3280 |
5465 |
60.02 |
5.18 |
0.376 |
CP |
297 |
6000 |
4.950 |
0.396 |
0.000 |
1669 |
6249 |
26.71 |
4.33 |
0.000 |
Trend for %MPCE: p=0.978 Trend for %PCE: p=0.027 |
Table 2 – summary of micronucleus induction by mmt (Trial 2, single treatment)
Sex |
Recovery Time |
Dose (mg/kg) |
‰MPCE (±SEM) |
%PCE (±SEM) |
Male |
24 |
0 |
2.2 ± 0.3 |
53.71 ± 5.54 |
50 |
3.3 ± 0.3 |
62.27 ± 3.70 |
||
75 |
2.5 ± 0.7 |
53.02 ± 4.69 |
||
100 |
2.7 ± 0.6 |
52.60 ± 5.47 |
||
Cyclophosphamide |
25 |
11.3 ± 2.9** |
|
|
Trend p= 0.293 p= 0.453 |
||||
|
48 |
0 |
3.4 ± 0.6 |
70.92 ± 4.52 |
75 |
1.8 ± 0.3 |
47.33 ± 4.96** |
||
100 |
3.5 ± 0.7 |
46.64 ± 3.94** |
||
Trend p= 0.715 p= 0.000 |
||||
Female |
24 |
0 |
1.6 ± 0.5 |
62.70 ± 3.22 |
50 |
1.8 ± 0.6 |
60.64 ± 3.07 |
||
75 |
2.0 ± 0.3 |
63.69 ± 4.35 |
||
100 |
2.1 ± 0.4 |
42.63 ± 2.46* |
||
Cyclophosphamide |
25 |
12.0 ± 1.3** |
|
|
Trend p= 0.190 p= 0.002 |
||||
|
48 |
0 |
1.6 ± 0.4 |
57.97 ± 3.83 |
|
|
75 |
1.6 ± 0.3 |
73.26 ± 4.67 |
|
|
100 |
1.2 ± 0.3 |
60.02 ± 7.35 |
Trend p= 0.190 p= 0.002 |
||||
Differences between sexes p= 0.0007 Differences between times p= 0.2593 |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Based on the findings, mmt administered in three consecutive days, or in one single dose did not present any adverse effect on the levels of micronucleated polychromatic erythrocytes. - Executive summary:
In a bone marrow micronucleus assay, two trials have been performed with male and female C57BL mice. In the first trial, mmt was administered to 5 males and 5 females per each dose level, 12.5, 25 and 50 mg/kg bw/day, for three consecutive days. For the second trial, the number of animals was the same, however the dose levels were 50, 75 and 100 mg/kg bw/day, and administration of the test compound was done in one single dose. For the first trial the sacrifice and sampling was performed 24-hours after the last administration, while for the second trial at 24 and 48-hours.
There was no evidence of toxicity at the concentrations tested, which were previously defined through a dose-range finding study. mmt did not cause a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any time. The positive control used was cyclophosphamide, and induced a significant increase MPCE as expected.
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