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EC number: 215-150-4 | CAS number: 1306-38-3
- 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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not applicable
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- ; however, the physico-chemical characterisation of the tested nano-CeO2 was of low quality but at the publication date the scientific community required less physico-chemical endpoints in such articles.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Not applicable
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: this OECD 471 study was well documented and met the generally accepted scientific principles.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Remarks:
- The GLP status was not specified in the article.
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- 0 (control), 50 to 5000 µg/plate (in triplicate)
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Nano-CeO2 was not soluble in water or common solvents - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: see below in "Details on test system and conditions"
- Details on test system and experimental conditions:
- POSITIVE CONTROLS
- in the absence of metabolic activation (-S9):
* N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at 3 μg/plate for TA100 and 5 μg/plate for TA1535
* 9-Aminoacridine (9AA) at 80 μg/plate for TA1537
* Mitomycin C (MMC) at 0.5 μg/plate for TA102
* 4-Nitroquinoline-1-oxide (4NQO) at 0.2 μg/plate for TA98
- in the presence of metabolic activation (+S9):
* 2-Aminoanthracene (2AA) at 1 μg/plate for TA100, 2 μg/plate for TA1535 and TA1537
* Benzo(a)pyrene (BP) at 5 μg/plate for TA98
* 1,8-Dihydroxyanthraquinone (DAN) at 10 μg/plate for TA102
DETERMINATION OF CYTOTOXICITY
- Method: growth of the bacteria background lawn - Evaluation criteria:
- No data available
- Statistics:
- No data available
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- - A cream-coloured film was observed at 1500 μg/plate and above with an associated precipitate at 5000 μg/plate. This observation did not, however, prevent the scoring of revertant colonies and confirmed that the samples were tested up to maximal dose level.
- No toxicity of the cerium oxide as no visible reduction in the growth of the bacteria background lawn at any dose level was observed both with and without metabolic activation.
- All of the positive control chemicals used in the study induced marked increase in the frequency of revertant colonies thus confirming the activity of the S9-mix and the sensitivity of the bacterial strains. - Conclusions:
- Nano-CeO2 was non-mutagenic to Salmonella typhimurium strains in this Ames test with and without metabolic activation at concentrations between 50 and 5000 µg/plate
- Executive summary:
Park B et al. (2007, 2008) investigated the genotoxic potential of nanometric cerium dioxide (nano-CeO2) in vitro.
A commercial nano-CeO2 from Oxonica was used in this study. These crystalline nanoparticles displayed a primary particle size of 9 nm and a specific surface area of 94.7 m²/g. The analysis of analytical purity showed that nano-CeO2 and its surface were composed of Ce and O. Moreover, nano-CeO2 was commercialised as aqueous slurry at an approximate concentration of 8%w/w.
The genotoxic potential of nano-CeO2 was determined by performing an Ames test, according to OECD guideline 471. Five strains of Salmonella typhimurium (i.e., TA 1535, TA 1537, TA 98, TA 100, TA 102) were treated with 50 to 5000 µg/plate of nano-CeO2 suspended in dimethyl sulfoxide (DMSO), in the presence or absence of metabolic activation.
All of the positive control chemicals used in the study induced marked increase in the frequency of revertant colonies thus confirming the activity of the S9-mix and the sensitivity of the bacterial strains.
The test showed no significant increases in the frequency of revertant colonies for any of the S. typhimurium strains, at any nano-CeO2 dose level, either with or without metabolic activation in any of the experiments. Moreover, nano-CeO2 induced no cytotoxicity as no visible reduction in the growth of the bacteria background lawn at any dose level was observed both with and without metabolic activation. A cream-coloured film was observed at 1500μg/plate and above with an associated precipitate at 5000 μg/plate.
Therefore, nano-CeO2 showed no mutagenic activity in this bacterial reverse mutation (Ames) test up to the limit concentration of 5000 µg/plate with or without metabolic activation.
There were no significant increases in the frequency of revertant colonies recorded for any of the strains of Salmonella, at any dose level, either with or without metabolic activation, as detailed in the table below.
Table 1: Summary of mean revertant colonies
Substance |
Dose Level (µg/plate) |
TA100 |
|
TA1535 |
|
TA102 |
|
|
|
(-S9) |
(+S9) |
(-S9) |
(+S9) |
(-S9) |
(+S9) |
Exp. 1 |
|
|
|
|
|
|
|
DMSO |
100 µL |
118 ± 7 |
97 ± 13 |
39 ± 3 |
32 ± 6 |
347 ± 29 |
351 ± 4 |
Nano-CeO2 |
50 150 500 1500 5000 |
100 ± 3 88 ± 13 84 ± 16 101 ± 13 101 ± 4 |
109 ± 17 115 ± 9 114 ± 20 115 ± 8 113 ± 7 |
37 ± 2 40 ± 3 33 ± 3 28 ± 4 39 ± 3 |
29 ± 13 36 ± 1 36 ± 3 32 ± 9 38 ± 2 |
356 ± 10 360 ± 13 377 ± 12 343 ± 38 343 ± 16 |
363 ± 25 381 ± 20 350 ± 17 330 ± 17 332 ± 14 |
Exp. 2 |
|
|
|
|
|
|
|
DMSO |
100 µL |
97 ± 14 |
132 ± 8 |
28 ± 6 |
30 ± 11 |
394 ± 9 |
380 ± 25 |
Nano-CeO2 |
50 150 500 1500 5000 |
99 ± 19 98 ± 20 84 ± 6 92 ± 8 95 ± 3 |
123 ± 17 127 ± 10 126 ± 11 133 ± 7 121 ± 22 |
32 ± 2 35 ± 6 35 ± 11 36 ± 8 28 ± 5 |
29 ± 5 40 ± 6 32 ± 4 36 ± 7 29 ± 3 |
359 ± 28 361 ± 32 382 ± 29 361 ± 43 371 ± 24 |
397 ± 39 391 ± 32 350 ± 7 313 ± 29 353 ± 36 |
|
|
TA98 |
|
TA1537 |
|
|
|
|
|
(-S9) |
(+S9) |
(-S9) |
(+S9) |
|
|
Exp. 1 |
|
|
|
|
|
|
|
DMSO |
100 µL |
28 ± 3 |
36 ± 7 |
13 ± 5 |
22 ± 2 |
|
|
Nano-CeO2 |
50 150 500 1500 5000 |
23 ± 5 25 ± 6 26 ± 6 22 ± 3 23 ± 4 |
36 ± 2 35 ± 6 35 ± 7 35 ± 1 37 ± 4 |
11 ± 5 12 ± 5 14 ± 5 14 ± 4 12 ± 2 |
18 ± 4 15 ± 5 17 ± 4 24 ± 2 20 ± 5 |
|
|
Exp. 2 |
|
|
|
|
|
|
|
DMSO |
100 µL |
21 ± 5 |
38 ± 7 |
12 ± 10 |
15 ± 6 |
|
|
Nano-CeO2 |
50 150 500 1500 5000 |
21 ± 4 22 ± 4 21 ± 4 19 ± 5 19 ± 3 |
33 ± 10 32 ± 2 32 ± 5 37 ± 4 26 ± 3 |
12 ± 1 14 ± 7 14 ± 4 9 ± 3 9 ± 1 |
13 ± 6 12 ± 4 16 ± 4 12 ± 3 17 ± 2 |
|
|
DETERMINATION OF CYTOTOXICITY
The negative control (polypropylene pipette tips) had a cytotoxicity grade of 0 and the positive control (tin-impregnated PVC strips) showed evidence of a moderate cytotoxicity with a grade 3 score; thus indicating that the assay system was reliable. Both bulk CeO2 and nano-CeO2 showed no evidence of cytotoxicity and each had a cytotoxicity grade of 0.
Table 2: Cytotoxicity results
Test material |
Mean cytotoxicity / reactivity grade |
Culture medium (vehicle control) |
0 |
Polypropylene pipette tips (negative control) |
0 |
Tin-impregnated PVC strips (positive control) |
3 |
Nano-CeO2 |
0 |
Bulk CeO2 |
0 |
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 007
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 008
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- EpiDerm "EPI-200" human epidermal model skin irritation test (as developed in MatTek Corporation, Ashland, MA, USA).
- GLP compliance:
- not specified
- Remarks:
- The GLP compliance status was not specified in this article
Test material
- Reference substance name:
- Cerium dioxide
- EC Number:
- 215-150-4
- EC Name:
- Cerium dioxide
- Cas Number:
- 1306-38-3
- Molecular formula:
- CeO2
- IUPAC Name:
- cerium dioxide
- Test material form:
- other: nanometric and micrometric materials in suspension
- Details on test material:
- - Name of test material: Nanometric cerium dioxide (nano-CeO2) received as aqueous slurry at an approximate concentration of 8%w/w; micrometric CeO2 (bulk)
- Supplier: Energenics Europe Ltd. (Envirox™) for nano-CeO2 and Aldrich for bulk CeO2
- Substance type: Monoconstituent substance
- Substance form: Nanoparticulate substance for nano-CeO2 and microparticulate substance for bulk CeO2
- Primary particle size (derived from BET): Mean particle size of 9 nm for nano-CeO2; 320 nm for bulk CeO2 (< 5 µm according to the supplier)
- Particle size distribution: No data available
- Stability: No data available
- Specific surface area (BET): 94.7 m²/g for nano-CeO2; 2.64 m²/g for bulk CeO2
- Surface charge: No data available
- Isoelectric point: No data available
- Shape: No data available
- Crystallinity (XRD): Cerianite for both nano-CeO2 and bulk CeO2
- Analytical purity: Nano-CeO2 and bulk CeO2 composed of Ce and O (EDX); 99.9% purity for bulk CeO2 (supplier’s data)
- Impurities: No data available
- Number density of nano-CeO2 in the suspension: No data available
- Cerium content in nano-CeO2 suspension: Aqueous slurry at an approximate concentration of 8%w/w nano ceria (as-received, according to the supplier)
- Solubility: No data available
- Oxidation degree: Cerium(IV) oxide for bulk CeO2 (supplier’s data)
- Surface properties (XPS): Surface chemistry of nano-CeO2 and bulk CeO2 => Ce, O
- Lot/batch No.: No data available
- Expiration date of the lot/batch: No data available
Further explanations on the physico-chemical characterisation of CeO2 nanoparticles are presented below in "any other information on materials and methods incl. tables".
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Vehicle:
- not specified
- Details on test system:
- EpiDermTM "EPI-200" HUMAN EPIDERMAL MODEL
The EpiDerm™ EPI-200 human epidermal model from MatTek Corporation (USA) was used in this study for assessment of the safety of Envirox™ since the skin is a potential route of exposure during the formulation and use of the nano-CeO2 containing diesel fuel additive when accidental skin contamination might reasonably be expected to occur.
1% (w/v) Triton X-100 and 1% of 20% (w/v) SLS were used as positive control and standard reference material, respectively. - Control samples:
- yes, concurrent positive control
- Amount/concentration applied:
- 50 mg of test substance applied
- Duration of treatment / exposure:
- Exposure times of 960, 1200 and 1440 minutes
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- other: mean irritation potential (MIP)
- Value:
- < 0.01
- Remarks on result:
- other: for nano-CeO2
- Remarks:
- - Basis: mean calculated as ET50 (reference material) / ET50 (test material). - Reversibility: no data.
- Irritation / corrosion parameter:
- other: MIP
- Value:
- 0.003
- Remarks on result:
- other: for bulk CeO2
- Remarks:
- - Reversibility: no data.
Any other information on results incl. tables
- EpiDermTM “EPI-200” HUMAN EPIDERMAL MODEL
Nano-CeO2 and bulk CeO2 did not directly reduce MTT. The ET50 values for nano-CeO2, 1% (w/v) TritonX-100 the positive control and 1% of 20% (w/v) SLS, a standard reference material, were 1517.18, 260.10 and 20.68 minutes respectively. The bulk CeO2 was assayed at a later time than nano-CeO2 and the corresponding ET50 values for bulk CeO2, the positive control and the reference material were > 1440, 410.60 and 46.22 minutes respectively.
A mean irritation potential (MIP) score was calculated as follows: MIP = ET50 (reference material) / ET50 (test material).
The MIP for both the nanometric and bulk CeO2 was calculated and determined as 0.01 for nano-CeO2 and 0.03 for bulk CeO2. Since both nanometric and bulk CeO2 had MIP values which were < 0.8 neither was considered to have the potential to be an in vivo skin irritant.
Test material |
Exposure time (min) |
Mean OD450 |
% viability |
ET50 min |
MIP |
Negative control |
960 1440 |
1.685 |
100 |
|
|
Nano-CeO2 |
960 1200 1440 |
2.010 1.138 1.089 |
119.29 67.54 64.53 |
1517.18 |
< 0.01 |
Bulk CeO2 |
960 1200 1440 |
1.994 1.975 1.729 |
92.87 97.36 86.23 |
> 1440 |
0.003 |
Positive control (1% TX100) |
240 360 480 |
1.035 0.212 0.095 |
61.42 12.58 5.64 |
260.10 |
< 0.18 |
Reference material 20% SLS |
15 30 60 120 |
0.983 0.710 0.273 0.100 |
58.34 42.14 16.20 5.93 |
20.68 |
1.00 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Since nano-CeO2 and bulk CeO2 had a mean irritation potential (MIP) value lower than 0.8, both materials were not considered to have the potential to be an in vivo skin irritant in this in vitro EpiDerm test.
- Executive summary:
Park B et al. (2007, 2008) investigated the skin irritating potential of nanometric cerium dioxide (nano-CeO2) and micrometric CeO2 (bulk CeO2) in vitro.
A commercial nano-CeO2 from Energenics Europe Ltd. (EnviroxTM) was used in this study. The nanoparticles displayed a mean primary size of 9 nm and a specific surface area of 94.7 m²/g. A bulk CeO2 was also added to the study. This micrometric material provided by Aldrich had a mean primary size of 320 nm and a specific surface area of 2.64 m²/g. The surface chemistry of both crystalline materials was evaluated and demonstrated that the surface of nanometric and bulk CeO2 was composed of Ce and O.
The EpiDerm™ EPI-200 human epidermal model from MatTek Corporation (USA) was used in this study for assessment of skin irritation. Fifty milligrams of test substance was applied to the human epidermal model for 960, 1200 and 1440 minutes. The irritation assessment was based on the measurement of cellular viability using the MTT assay. A mean irritation potential (MIP) score was calculated as follows: MIP = ET50 (reference material) / ET50 (test material) where ET50 was the exposure time at which relative value of optical density was 50% of the negative control and the reference material was SLS (1% of 20% (w/v)).
Nano-CeO2 exposure induced variations of cellular viability: 119.3% at 960 minutes, 67.5% at 1200 minutes, 64.5% at 1440 minutes. Exposure to bulk CeO2 caused no or only few changes in cell viability: 92.87% at 960 minutes, 97.36% at 1200 minutes, 86.23% at 1440 minutes. As nanoparticles and bulk material had a MIP value lower than 0.8 (i.e., < 0.01 for nano-CeO2 and 0.003 for bulk CeO2), both nano- and micro-CeO2 were not considered to have the potential to be an in vivo skin irritant based on this in vitro EpiDerm test.
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