Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
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: 215-150-4 | 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
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2019
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- The test substance was not fully characterized for nano characterisation parameters. The methods and results are reported quite briefly.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 019
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Qualifier:
- according to guideline
- Guideline:
- other: Franz method
- Version / remarks:
- As published in: Guth, K.; Schäfer-Korting, M.; Fabian, E.; Landsiedel, R.; van Ravenzwaay, B. Suitability of skin integrity tests for dermal absorption studies in vitro. Toxicol. In Vitro 2015, 29, 113–123.
- Qualifier:
- according to guideline
- Guideline:
- other: EDETOX protocols
- Version / remarks:
- As published in: Sandt, J.J.; Burgsteden, J.A.; Cage, S.; Carmichael, P.L.; Dick, I.; Kenyon, S.; Korinth, G.; Larese, F.;
Limasset, J.C.; Maas, W.J.; et al. In vitro predictions of skin absorption of caeine, testosterone, and benzoic acid: A multi-centre comparison study. Regul. Toxicol. Pharmacol. 2004, 39, 271–281.
- GLP compliance:
- not specified
- Remarks:
- The GLP status was not specified in the 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:
- solid: nanoform
- Details on test material:
- - State of aggregation:
no data
- Particle size distribution: 17 +/- 5 nm (TEM),
- Mass median aerodynamic diameter (MMAD): no data
- Geometric standard deviation (GSD): no data
- Shape of particles: various shapes, ranging from spherical to polyhedral (TEM).
- Surface area of particles: no data
- Crystal structure: yes. Crystalline CeO2 was confirmed by Raman spectroscopy, with the presence of the characteristic peak at 464 cm-1, plus two broad and barely visible peaks at lower
(~255 cm-1) and higher (~590 cm-1) energy. The sharp and symmetric shape of the peak, and its Raman shift (464 cm-1), qualitatively indicated a large size of the ceria particles
- Coating: no data
- Surface properties: no data
- Density: no data
- Moisture content: no data
- Residual solvent: no data
- Activation: no data
- Stabilisation: no data
- Other: in house synthesized by a hydrothermal route using Cerium ammoniumnitrate (purity, 99.99 %) and a synthetic sweat solution as precursors.
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- other: Human
- Strain:
- other: not applicable
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Not appropriate. See information reported in the section "Details on study design".
Administration / exposure
- Type of coverage:
- other: no applicable
- Vehicle:
- other: synthetic sweat
- Duration of exposure:
- 24 hoours
- Doses:
- 0,6 mg cerium dioxide/cm2 corresponding to 0,220 ml of the donor solution (synthetic sweat).
- No. of animals per group:
- not applicable
- Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: Human abdominal full-thickness skin was obtained as surgical waste from two female donors aged 45–65 years. Others donors were men and women with an age range of 45–71 years.
- Ethical approval if human skin: yes. The study was approved by the Trieste Hospital Ethical Committee n° 236/2007.
- Type of skin: Human abdominal full-thickness skin
- Preparative technique: After the skin excision, subcutaneous fat was removed with a scalpel blade and hair was shaved from the epidermis. Two different experiments were conducted using intact and damaged skin.
- Thickness of skin (in mm): approximately 1 mm.
- Membrane integrity check: Yes. Skin integrity was assessed using the transepidermal water loss (TEWL) method as described by Guth et al. (2015). Cells with a value of >10 g/m2/h were considered to be damaged and rejected.
- Storage conditions: Skin samples were stored at -25 °C for a period up to, but not exceeding, four months. It has been demonstrated that this procedure does not damage skin barrier properties. On the day of the experiment, skin samples were defrosted in a physiological solution at room temperature for a 30-min period and 2 x 2 cm2 pieces were cut from each skin specimen and mounted separately on the diffusion cells.
- Justification of species, anatomical site and preparative technique: no data
PRINCIPLES OF ASSAY
- Diffusion cell: Franz cell
- Receptor fluid: physiological solution. The physiological solution used as the receptor phase was prepared by dissolving 2.38 g of Na2HPO4, 0.19 g of KH2PO4, and 9 g of NaCl into 1 L of Milli-Q water (final pH 7.35). The salt concentration in the receiving fluid was approximately the same as that found in blood.
- Solubility od test substance in receptor fluid: No data.
- Static system: Yes
- Flow-through system:
- Test temperature: 32 ° C
- Humidity: no data
- Occlusion: no
- Reference substance(s): no
- Other
Donor fluid: synthetic sweat solution consisting of 0.5% sodium chloride, 0.1% urea, and 0.1% lactic acid in Milli-Q water, and pH was adjusted to 4.5 using a concentrated ammonia solution. The authors indicated that the cerium concentration in the donor phase, which was collected at the beginning of the test after the removal of the NPs by ultrafiltration, was less than 0.05% of the starting suspensions and did not change at the end of the experiments.
Results and discussion
- Signs and symptoms of toxicity:
- not examined
- Remarks:
- in vitro study
- Dermal irritation:
- not examined
- Remarks:
- in vitro study
- Absorption in different matrices:
- - Receptor fluid, receptor chamber, donor chamber (in vitro test system):
The cerium concentration in the donor phase, which was collected at the beginning of the test after the removal of the NPs by ultrafiltration, was less than 0.05% of the starting suspensions and did not change at the end of the experiments.
In the experimental condition, the used Ce did not permeate the intact skin since the concentration in the receiving phase was the same as that of the blank cells (2.0 +/- 0.4 ng/cm2) after 24 hours. However, it reached 3.3 +/- 0.7 ng/ cm2 for damaged skin (p = 0.008).
The amount of Ce (µg/cm2) inside whole skin was 3.64 +/- 0.15 for intact skin, 7.07 +/- 0.78 for damaged skin, and 0.19 +/- 0.06 for blank cells (mean +/- SD). The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 +/- 0.71 µg/cm2 and 0.39 +/- 0.16 µg/cm2, respectively).
Microscopic analysis confirmed the low penetration and permeation of CeO2 NPs since only a small signal of Ce was revealed in the epidermis of an intact skin sample but NPs were not
visualized by TEM investigation.
- Skin preparation (in vitro test system): see above in "Details on in vitro test system" and "Any other information on materials and methods incl tables"
- Stratum corneum (in vitro test system): not applicable.
Percutaneous absorptionopen allclose all
- Key result
- Time point:
- 24 h
- Dose:
- vehicle (synthetic sweat)
- Parameter:
- amount
- Remarks:
- Amount of Ce that penetrate into the whole skin.
- Absorption:
- ca. 0.19 other: µg/cm2
- Remarks on result:
- other: For blank cells
- Key result
- Time point:
- 24 h
- Dose:
- 0,6 mg CeO2 /cm2
- Parameter:
- amount
- Remarks:
- Amount of Ce that penetrate into the whole skin.
- Absorption:
- ca. 3.64 other: µg/cm2
- Remarks on result:
- other: for intact skin.
- Key result
- Time point:
- 24 h
- Dose:
- 0,6 mg CeO2/cm2
- Parameter:
- amount
- Remarks:
- Amount of Ce that penetrate into the whole skin.
- Absorption:
- ca. 7.07 other: µg/cm2
- Remarks on result:
- other: For damaged skin
- Key result
- Time point:
- 24 h
- Dose:
- vehicle (synthetic sweat)
- Parameter:
- amount
- Remarks:
- Amount of Ce that penetrate into the dermis layer.
- Absorption:
- > 0 - <= 0.1 other: µg/cm2
- Remarks on result:
- other: For blank cells
- Key result
- Time point:
- 24 h
- Dose:
- 0,6 mg CeO2/cm2
- Parameter:
- amount
- Remarks:
- Amount of Ce that penetrate into the dermis layer.
- Absorption:
- ca. 0.39 other: µg/cm2
- Remarks on result:
- other: For intact skin
- Key result
- Time point:
- 24 h
- Dose:
- 0,6 mg CeO2/cm2
- Parameter:
- amount
- Remarks:
- Amount of Ce that penetrate into the dermis layer.
- Absorption:
- ca. 2.93 other: µg/cm2
- Remarks on result:
- other: For damaged skin.
- Key result
- Time point:
- 24 h
- Dose:
- vehicle (synthetic sweat)
- Parameter:
- amount
- Remarks:
- Ce concentration in the receiving solution
- Absorption:
- ca. 2 other: ng/cm2
- Remarks on result:
- other: Blank Cells
- Key result
- Time point:
- 24 h
- Dose:
- 0,6 mg CeO2/cm2
- Parameter:
- amount
- Remarks:
- Ce concentration in the receiving solution.
- Absorption:
- ca. 2 other: ng/cm2
- Remarks on result:
- other: For intact skin.
- Key result
- Time point:
- 24 h
- Dose:
- 0,6 mg CeO2/cm2
- Parameter:
- amount
- Remarks:
- Ce concentration in the receiving solution
- Absorption:
- ca. 3.3 other: ng/cm2
- Remarks on result:
- other: For damages skin.
Applicant's summary and conclusion
- Conclusions:
- The authors concluded that their data showed a very low dermal absorption and transdermal permeation of cerium dioxide nanoparticles.
- Executive summary:
Mauro M. et al, (2019) performed an in vitro investigation of the permeation of in-house syntesized 17-nm CeO2 NPs dispersed in synthetic sweat (1 g/L) using excised human skin on Franz cells. The study was performed according to OECD guideline n° 428, but no information on the GLP status was indicated in the article. Thus, the study was scored as validity 2 according to Klimisch criteria. Experiments were performed using intact and needle-abraded skin, separately.
In intact and damages skin permeation experiments at time 0, the exposure chambers of three Franz dffusion cells were filled with 0.220 mL of the donor solution, corresponding to an amount of CeO2 of 0.6 mg/cm2. The experiment was repeated twice. After the integrity test, the receiving solutions and the skin pieces were removed and analysed for CeO2 content.
After 24 hours, the average amount of Ce into intact and damaged whole skin samples was 3.64 +/- 0.15 and 7.07 +/- 0.78 µg/cm2, respectively. Ce concentration in the receiving solution was 2.0 +/-0.4 (as in the blank cells) and 3.3 +/- 0.7 ng/cm2 after 24 h. The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 +/- 0.71 µg/cm2 and 0.39 +/- 0.16 µg/cm2, respectively).
The authors concluded that CeO2 NPs could not permeate intact skin, but this permeation was possible—if at a low level—using an abraded skin protocol. A low amount of cerium was present in intact and damaged skin samples after prolonged exposure (24 h) to CeO2NPs. They further suggested that this behavior is probably due to the very low ionization of these metal oxides in synthetic sweat, resulting in a small concentration of free metal ions in the donor phase being able to cross over the physiological barriers. The NPs’ capability of permeating the dermal layers is lower with respect to the free ions, and depends on their physicochemical characteristics.
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.