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EC number: 231-111-4 | CAS number: 7440-02-0
- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- not reported
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards.
Data source
Reference
- Reference Type:
- publication
- Title:
- In vitro embryotoxicity testing of metals for dental use by differentiation of embryonic stem cell test
- Author:
- Imai K. and M. Nakamura
- Year:
- 2 006
- Bibliographic source:
- Congenital Anomalies. 46:34–38
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: embryonic stem cell test (EST) protocol (Scholz et al. 1999)
- Principles of method if other than guideline:
- Test conducted according to: Scholz G, Pohl I, Genschow E, Klemm M, Spielmann H (1999) Embryotoxicity screening using embryonic stem cells in
vitro: Correlation to in vivo teratogenicity. Cells Tissues Organs 165: 203–211. - GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Nickel(2+) metal
- IUPAC Name:
- Nickel(2+) metal
- Reference substance name:
- Nickel
- EC Number:
- 231-111-4
- EC Name:
- Nickel
- Cas Number:
- 7440-02-0
- Molecular formula:
- Ni
- IUPAC Name:
- nickel
- Reference substance name:
- atomic absorption spectroscopy (Wako; 1000 ppm, Japan)
- IUPAC Name:
- atomic absorption spectroscopy (Wako; 1000 ppm, Japan)
- Reference substance name:
- Metal powder
- IUPAC Name:
- Metal powder
- Details on test material:
- - Name of test material (as cited in study report): Metal powder
- Molecular formula (if other than submission substance): Not different than submission substance
- Molecular weight (if other than submission substance): Not different than submission substance
- Smiles notation (if other than submission substance): Not different than submission substance
- InChl (if other than submission substance): Not different than submission substance
- Structural formula attached as image file (if other than submission substance): Not different than submission substance
- Substance type: Pure product
- Physical state: Solid, metal powder
- Other details on test material not reported or not applicable
Constituent 1
Constituent 2
Constituent 3
Constituent 4
Test animals
- Species:
- mouse
- Strain:
- other: embryonic stem cells (ES) from the D3 mouse cell line
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Embryonic stem cells (ES) from the D3 mouse cell line and clone A31 from Balb/c 3T3 cells (3T3 cells) from mice.
The 3T3 cells were purchased from American Type Culture Collection (ATCC; Cat. No. CCL-163).
- Other information not reported or not applicable
ENVIRONMENTAL CONDITIONS: Not applicable
IN-LIFE DATES: Not applicable
Administration / exposure
- Route of administration:
- other: Cell culture
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Culture mediums For ES-D3 cells, preheat treated 20% (v/v) fetal calf serum (FCS) (Hyclone, USA) was added to 1% (v/v) nonessential amino acids
(Gibco, USA), 0.1 mM β-mercaptoethanol (Sigma, USA), 2 mM L-glutamine (Gibco), and Dulbecco’s Modified Eagle Medium (DMEM) (Gibco) with
penicillin/streptomycin (Gibco). Except during tests, 1000 U/mL of mouse leukemic inhibitory factor (mLIF) was added to inhibit natural cell
differentiation. For 3T3 cells, a culture medium was prepared by adding 10% (volume ratio) FCS to DMEM with 4 mM L-glutamine and penicillin/
streptomycin.
Differentiation assay: ES-D3 cells were added to each test solutions at a range of solution concentrations. The number of ES-D3 cells were adjusted
to a final concentration of 3.75 × 10^4 cells/mL in each test solution using a hemacytometer, and 20 μL cell suspension was dropped 60–70
times onto the inner side of the lid of a 10-cm diameter Petri dish using a micropipette. Each drop of the cell suspension contained approximately
750 cells. Five ml of sterilized phosphate buffered saline (PBS) was poured into the Petri dish, and the lid was quickly reversed and placed on to the
dish before the cell suspension on the lid could flow down. Suspension culture was carried out for three days in a CO2 incubator (5% CO2 and 95%
air; 37°C) (Sanyo, Japan). Drops of the cell suspension on the inside of the Petri dish lid were then collected into a 6-cm diameter Petri dish. The test
solutions were replaced with fresh ones using a pipette and each test solution was subjected to further reaction for two days in the same condition.
Subsequently, two 24-well multidishes were used for every test solution. Each of the embryoid bodies (EBs) formed were placed into a well with a
micropipette, and the EBs were cultured statically for five days. The presence of beating myocardial cells in each well was examined under an inverted phase difference microscope (IX-70, Olympus, Japan). The number of wells in which beating cells were observed at each test solution concentration was examined, and the ID50 was calculated from the ratio of the number of the wells to the number of wells in which EBs were successfully
disseminated.
Cell viability assay: In order to examine the effects of the test solutions on the two kinds of cells, i.e. 3T3 cells and ES cells, cell suspensions of
1 × 10^4 cells/ mL were prepared in the absence of mLIF, inoculated into a 96-well multidish, and test solutions were added to each well after 2 h.
Finally, the cell viability assay was performed on day 10 of the culture. Cell viability measurements were made using a
(3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl terazolium bromide, Sigma, USA) MTT assay. MTT 100 mg was dissolved in 200 mL PBS, and
20 μL was placed into each well. After 2 h incubation, the MTT solution was removed using a Pasteur-pipette, and exactly 130 ìL
acid isopropanol solution was added to each well in order to measure absorbance at 570 nm by ELISA reader (SpectraMax Plus,
Molecular Device, USA).
DIET PREPARATION: Not applicable
VEHICLE: Not applicable - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations of metallic elements in the extracts were measured with a sequential radiofrequency plasma emission spectrometer
(ICPS-1000IV; Shimadzu, Japan), and each test solution was obtained by serial dilution. - Details on mating procedure:
- Not applicable
- Duration of treatment / exposure:
- Not applicable
- Frequency of treatment:
- Not applicable
- Duration of test:
- Not applicable
- No. of animals per sex per dose:
- Not applicable
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Not applicable
Examinations
- Maternal examinations:
- Not applicable
- Ovaries and uterine content:
- Not applicable
- Fetal examinations:
- Not applicable
- Statistics:
- The results are expressed as the mean and the confidence interval of 95%. Each data point represented four independents experiments
where three independents wells were used for the one experiment. P-values less than 0.05 were regarded as significant. - Indices:
- Not applicable
- Historical control data:
- Not applicable
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no data
Details on maternal toxic effects:
Not applicable
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- other: IC50
- Effect level:
- 91 other: uM Ni
- Basis for effect level:
- other: other:
- Dose descriptor:
- other: IC50
- Effect level:
- 79.7 other: uM Ni
- Basis for effect level:
- other: other:
- Dose descriptor:
- other: ID50
- Effect level:
- 75.8 other: uM Ni
- Basis for effect level:
- other: other:
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
The authors reported that the test results indicated that nickel has no embryotoxicity and this in conflict with the previous reports.
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The authors reported that the test results indicated that nickel has no embryotoxicity.
- Executive summary:
STUDY RATED BY AN INDEPENDENT REVIEWER.
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