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EC number: 234-988-1 | CAS number: 12049-50-2
- 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 corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From July 10, 2017 to September 07, 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- Calcium titanium trioxide
- EC Number:
- 234-988-1
- EC Name:
- Calcium titanium trioxide
- Cas Number:
- 12049-50-2
- Molecular formula:
- Ca.O3Ti
- IUPAC Name:
- Calcium titanium trioxide
- Reference substance name:
- Titanium dioxide
- EC Number:
- 236-675-5
- EC Name:
- Titanium dioxide
- Cas Number:
- 13463-67-7
- Molecular formula:
- O2Ti
- IUPAC Name:
- dioxotitanium
- Reference substance name:
- Silicon dioxide
- EC Number:
- 231-545-4
- EC Name:
- Silicon dioxide
- Cas Number:
- 7631-86-9
- Molecular formula:
- O2Si
- IUPAC Name:
- Silicon dioxide
- Reference substance name:
- Aluminium oxide
- EC Number:
- 215-691-6
- EC Name:
- Aluminium oxide
- Cas Number:
- 1344-28-1
- Molecular formula:
- Al2O3
- IUPAC Name:
- oxo(oxoalumanyloxy)alumane
- Reference substance name:
- Magnesium oxide
- EC Number:
- 215-171-9
- EC Name:
- Magnesium oxide
- Cas Number:
- 1309-48-4
- Molecular formula:
- MgO
- IUPAC Name:
- magnesium oxygen(-2) anion
- Reference substance name:
- Diniobium pentaoxide
- EC Number:
- 215-213-6
- EC Name:
- Diniobium pentaoxide
- Cas Number:
- 1313-96-8
- Molecular formula:
- Nb2O5
- IUPAC Name:
- diniobium pentoxide
- Test material form:
- solid: nanoform, surface-treated
Constituent 1
impurity 1
impurity 2
impurity 3
impurity 4
impurity 5
In vitro test system
- Test system:
- human skin model
- Source species:
- other: Reconstructed human epidermis (Epiderm™)
- Source strain:
- other: 00267
- Details on animal used as source of test system:
- Not applicable
- Justification for test system used:
- The method followed, described in XcellR8 SOP L0048 'Epiderm™ In Vitro Reconstructed Human Epidermis Skin Corrosion Test', is based on the current MatTek Protocol (MK-24-007-0024, 2014-11-07) using the MatTek Corporation Epiderm™ reconstructed tissue model: EPI-200. This method was endorsed in 2002 by National Co-ordinators of OECD Test Guideline Programme (WNT), originally adopted in 2004 and updated in 2013 and 2015. The Epiderm™ skin model and assay for skin corrosion testing is endorsed by OECD TG 431.
- Vehicle:
- water
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Epiderm™ (EPI-200) Reconstructed Human Epidermis
- Tissue batch number(s): Lot 25834
- Delivery date: August 01, 2017 (tissues kept at 4°C until use)
- Date of initiation of testing: July 11, 2017
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during pre-incubation: 37°C (5 % CO2, ≥95 % RH)
- Temperature used during treatment / exposure: 37°C (5 % CO2, ≥95 % RH)
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- Spectrophotometer: BMG LabTech FluoStar Optima (calibrated July 24, 2017)
- Wavelength: 570 nm
- Filter: No
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: Optical density = 1.866 ± 0.143 (mean and SD of MTT value of three tissues exposed to H2O). PASS: Test guideline acceptance range = ≥0.8 and ≤2.8
- Barrier function: ET 50% of tissues exposed to 100 μl Triton X-100 1%, n = 3 = 6.02 h. PASS: Test guideline acceptance range = ≥4.0 and ≤8.7 h
- Morphology: Histological examination demonstrated human epidermis-like structure: including multiple layers (at least 4) of viable epithelial cells (basal layer, stratum spinosum, stratum granulosum) which are present under multi-layered stratum corneum (PASS). Tissue thickness = 129.1 μm (11 layers). PASS. Acceptance range = >70 and <130 μm
- Contamination: No evidence of contamination during long term antibiotic and antimycotic free culture. PASS: No contamination reported
NUMBER OF REPLICATE TISSUES: Triplicate
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: A preliminary test was undertaken to check the potential of the test item to interfere with the MTT viability test endpoint. This was followed by the main experiment
DECISION CRITERIA
- The test substance is considered to be corrosive to skin if the mean OD570 of the negative control tissues is <0.8 after 3 min and 1 h; the mean of the positive control relative percentage viability after 1 h exposure is <15 % of the mean of the negative control; and the coefficient of variation (CV) is <0.3 (30 %) - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: Nominal 25 mg-neat to the surface of the Epiderm™ skin model
VEHICLE
- Amount applied: 25 μl
NEGATIVE CONTROL
- Concentration: Neat
- Lot/batch no.: RNBF8521
POSITIVE CONTROL
- Concentration: Single topical application in ultrapure water of 8N
- Lot/batch no.: SLBD3295V
- Purity: ≥85 % - Duration of treatment / exposure:
- 3 and 60 min
- Number of replicates:
- Triplicate
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- (% to negative control)
- Run / experiment:
- 3 minutes
- Value:
- 101.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- (% to negative control)
- Run / experiment:
- 60 minutes
- Value:
- 106.4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Visible damage on test system: No
- Direct-MTT reduction: The test item was found not to interfere
- Colour interference with MTT: The test item was found not to interfere
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes, the mean OD570 was >0.8: 1.668 after 3 minutes and 1.546 after 1 hour
- Acceptance criteria met for positive control: The mean relative percentage viability after 1 hour exposure was >15 % (23 %) of the mean negative control, suggesting a failed criteria. However, it is still possible to classify the positive control as Corrosive (Category 1A) as the mean viability value after 3 minutes was <25 % (19.3 %). Additionally, KOH is an MTT interfering compound and the subtraction of interfering values would have led to a viability percentage below 15 %. Subsequently, the results are considered to be valid
- Acceptance criteria met for variability between replicate measurements: Yes, the coefficient of variation (CV) for the triplicate measurements did not exceed 0.3 (i.e. 30 %) in any circumstance
Any other information on results incl. tables
Mean and SD of Cell Viability Measurements after 3 Minutes and 1 Hour of Application:
Material | 3 Minutes | 1 Hour | Prediction (OECD TG 431) | ||||
Mean of Viability (%) | SD of Viability | CV (%) | Mean of Viability (%) | SD of Viability | CV (%) | ||
Negative Control | 100 | 9.3 | 9.3 | 100 | 3.8 | 3.8 | Non-Corrosive |
Positive Control |
19.3 | 5.6 | 29.2 | 23 | 4.5 | 19.4 | Corrosive (Category 1A) |
Test Item |
101.9 | 20.8 | 20.4 | 106.4 | 3.1 | 2.9 | Non-Corrosive |
The test item did not reduce the viability below 50 % after 3 minutes nor below 15 % after 1 hour and should be considered as non-corrosive.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In an in vitro skin corrosion experiment using reconstructed human epidermis (RHE), calcium titanium trioxide resulted in a mean tissue viability (% of the negative control) of 101.9 % after 3 minutes and 106.4 % after 1 hour. Subsequently, calcium titanium trioxide cannot be classified as corrosive to human skin (CLP Regulation (EC) No. 1272/2008).
- Executive summary:
To determine the corrosion potential of calcium titanium trioxide to human skin, an in vitro experiment was performed according to Good Laboratory Practise (GLP) and OECD Guideline 431 (Reconstructed Human Epidermis (RHE) Test Method) without deviation. MatTek Corporation Epiderm™ reconstructed tissue model (EPI-200) was used, which comprises normal human-derived epidermal keratinocytes cultured to form a multi-layered highly differential model of the human epidermis. As skin corrosion is related to cytotoxicity in the Epiderm™ tissue, determined by the reduction of MTT to formazan by viable cells relative to a negative control, the results offer a robust foundation from which true corrosivity can be predicted.
A preliminary test was undertaken to establish the potential of calcium titanium trioxide to interfere with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) viability endpoint. No interference (water colouration or MTT interference) from calcium titanium trioxide was detected. Following pre-incubation for 1 hour, the surface of Epiderm™ was exposed to a single topical application of 25 µl H20 plus nominal 25 mg / 50 µl neat test or reference items for a time period of 3 minutes or 1 hour (n = 3). The negative control consisted of sterile water (tissue grade) and the positive control of potassium hydroxide (KOH) in ultrapure water. After 3 minutes and 1 hour, tissues were tested for MTT viability. Tissue viability was assessed as a percentage and compared to the negative control.
The acceptance criteria for the negative and positive control were satisfied and all results were deemed to be valid. The OD570 of the negative control was >0.8 after 3 minutes (1.668) and 1 hour (1.546) and the mean viability of the positive control was <15 % (when interfering values have been removed). The percentage viability of the reconstructed human tissue was 101.9 and 106.4 % after 3 minutes and 1 hour of exposure, respectively. As the test item did not reduce viability below 50 % after 3 minutes, nor below 15 % after 1 hour, it was concluded that calcium titanium trioxide is not corrosive to human skin and cannot be classified as such according to CLP Regulation (EC) No. 1272/2008.
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