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EC number: - | CAS number: -
- 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:
- 2021-01-12 to 2021-01-15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- 2015-07-28
- Deviations:
- yes
- Remarks:
- OECD 439 (2020): Pre-test for colour interference was carried out using the MatTek Protocol, i.e. only performed with test chemical in water and no spectral analysis in the range of 570 nm. No historical data of pos. and neg. control are available.
- GLP compliance:
- yes
Test material
- Reference substance name:
- titanium, chromium, iron, zinc oxide
- Molecular formula:
- x(Zn, Ti, Cr, Fe)3O4 * yTiO2 * z(Fe, Cr, Zn, Ti)3O5
- IUPAC Name:
- titanium, chromium, iron, zinc oxide
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Chemical description: Chromium, iron, titanium and zinc spinel and rutile
- Physical state: Solid, brown powder, odourless
- Crystal Structure: Spinel and rutile
- Storage condition of test material: Kept dry in closed containers
- Purity : ca 98%
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- other: normal, human epidermal keratinocytes
- Cell source:
- other: humans
- Source strain:
- other: not applicable
- Details on animal used as source of test system:
- not applicable
- Justification for test system used:
- This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human-derived epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely resembles the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDermTM (EPI-200-SITor EPI-212-SIT; MatTek)
- Tissue lot number: 33786
TEST FOR MTT INTERFERENCE
Approximately 25 mg test substance was added to 1.0 mL of MTT medium in a clear glass vial. After 60 minutes of incubation at 37.2 - 37.4 °C, in an atmosphere containing 5 % CO2, the mixture was shaken and evaluated for presence and intensity of staining/coloration. A vial of MTT medium served as a control. No change was noted.
TEST FOR COLOUR INTERFERENCE
25 mg of test substance was added to 0.3 mL of deionized water, in a clear glass vial. After 60 minutes of incubation at 37.2 - 37.4 °C, in an atmosphere containing 5 % CO2, the mixture was shaken and evaluated for presence and intensity of staining/coloration. No change was noted.
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE AND COLOUR INTERFERENCE
Since the test item-water solution did not change colour and the test item did not interfere with MTT, no additional tissues were necessary in the main experiment.
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37.1 - 37.2 °C and ambient temperature
- Temperature of post-treatment incubation: 37.2 - 37.3 °C
REMOVAL OF TEST MATERIAL AND CONTROLS
- The tissues were rinsed with sterile DPBS by filling and emptying the tissue insert at least 15 times to remove any residual test material. A constant stream of DPBS was to dislodge the test substance. Cotton swabs were also used to aid in removal of the residual test material.
- After the last rinse, the insert was completely submerged 3 times in a container filled with 150 mL DPBS while gently swishing. The tissue insert was rinsed inside and out with sterile DPBS one final time and the insert was gently shaken and blotted to remove excess liquid.
EXPOSURE
- After the pre-incubation at 37.1 - 37.3 °C and 5 % CO2 for 60 minutes, the inserts were transferred from the upper wells to fresh media in the lower wells of the 6-well plate and further incubated overnight for ~ 18 hours at 37.0 - 37.1 °C and 5 % CO2.
- The upper row of three, 6-well plates were filled with 0.9 mL of assay medium per well. Two plates were prepared for each test substance and one plate for the control substance. Pre-incubated plates were removed from the incubator a few minutes before exposure to the chemicals.
- The tissues were wetted with 25 µL DPBS prior to application.
- Approximately 25 mg of the test substance, and 30 μL of negative control or positive control were added to the surface of three single viable tissues. The tissues were placed in the incubator (37 °C, 5 % CO2) for 35 ± 1 minutes. Then all tissues were removed from the incubator and placed in the sterile hood at ambient temperature until a total of 60 ± 1 minutes.
- The tissue inserts were transferred to previously prepared 6-well plates containing 0.9 mL of assay medium in 3 wells (top row). The tissues were swabbed to remove moisture from the surface. The tissues were incubated for 26 hours at 37.2 - 37.3 °C and 5 % CO2. The plates were removed, and the remaining 3 lower wells were filled with 0.9 mL of fresh assay medium. The inserts were transferred to the freshly filled wells and the plates were placed back into the incubator for an additional ~20 hours at 37.2 - 37.3 °C and 5 % CO2.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT
- MTT concentration: 1 mg/mL
- Incubation time: ~3 hours (37.2 - 37.3 °C, 5 % CO2)
- Inserts were removed from the 6-well plates, and residual media was blotted as needed and transferred into appropriately labelled wells of a 24-well plate containing 300 μL of prepared MTT medium or a blank well. The plates were incubated.
- After the 3 hour, the MTT medium was aspirated from all the wells and discarded appropriately. The wells were rinsed with DPBS three times. After the final rinse was aspirated, the inserts were transferred to a fresh 24-well plate. One mL of isopropanol (extraction solution MTT-100-EXT) was added to each insert and the plate was sealed with Parafilm®. Extraction was performed for 2 hours at room temperature on a shaker (120 rpm). The tissues were discarded and an additional 1 mL of isopropanol was added to the well. The extract in each well was mixed and then duplicate 200 μL aliquots of each were transferred into a 96-well flat bottom microtiter plate using the plate design below for OD measurement. Isopropanol was used as blanks.
NUMBER OF REPLICATE TISSUES:
- Three tissue replicates for test item and controls
PREDICTION MODEL / DECISION CRITERIA
Optical density (OD) was measured in a 96-well plate spectrophotometer using a wavelength of 570 nm, without a reference filter.
Using the resulting OD, viability of the tissue for each treatment group was determined:
Relative viability TS (%) = [ODTS / Mean of ODNC] x 100
Relative viability NC (%) = [ODNC / Mean of ODNC] x 100
Relative viability PC (%) = [ODPC / Mean of ODNC] x 100
For each test substance, negative control, and positive control, the mean relative viability of the tissues was calculated and used for classification. If the mean tissue viability is ≤ 50%, the test substance is predicted to be an irritant (GHS Category 2). If the mean tissue viability is >50%, a non-irritant is confirmed. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied: Three tissue replicates were wetted with 25 µL of DPBS prior to application and then 25 mg of the neat test substance was added to the viable tissue surface.
VEHICLE
- Amount(s) applied: not applicable
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DPBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL of 5 % SDS solution - Duration of treatment / exposure:
- 60 minutes
- Duration of post-treatment incubation (if applicable):
- ~46 hours
- Number of replicates:
- Number of EpiDerm tissues per group: triplicates
Results and discussion
In vitro
Results
- Irritation / corrosion parameter:
- % tissue viability
- Value:
- 101.8
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- TEST FOR MTT INTERFERENCE
In the pre-experiment for MTT interference the test item did not reduce MTT to Formazan salt.
TEST FOR COLOUR INTERFERENCE
In the pre-experiment for colour interference the test item did not change colour when mixed with deionised water.
DEMONSTRATION OF TECHNICAL PROFICIENCY:
Prior to routine use of EpiDermTM for regulatory purposes, the laboratory demonstrated technical proficiency by correctly predicting the ten proficiency chemicals listed in Table 1 of OECD TG 439. The respective Laboratory Technical Proficiency Data are attached in the field "Overall remarks, attachments" below.
ACCEPTANCE OF RESULTS:
- the mean OD570 of the tissue replicates treated with the negative control is ≥ 0.8 and ≤ 2.8 (1.994) in accordance with OECD TG 439.
- the viability of the tissue replicates treated with the positive control is ≤ 20% (2.6).
- the standard deviation from individual % tissue viablitiies calculated from 3 identically treated replicates is ≤ 18 (0.13 - 3.34).
Any other information on results incl. tables
Optical density and viability results I
Treatment Group |
Tissue No. |
Raw data OD 570 nm |
Blank Corrected data OD 570 nm |
Mean OD of aliquots |
% of viability |
||
Aliq. 1 |
Aliq. 2 |
Aliq. 1 |
Aliq. 2 |
||||
Blank |
|
- |
- |
- |
- |
0.0872 |
- |
Negative Control |
1 |
2.0752 |
2.1466 |
1.988 |
2.059 |
2.024 |
101.5 |
2 |
1.9928 |
2.0178 |
1.906 |
1.931 |
1.918 |
96.2 |
|
3 |
2.1368 |
2.1205 |
2.050 |
2.033 |
2.041 |
102.4 |
|
Positive Control |
1 |
0.1404 |
0.1417 |
0.053 |
0.055 |
0.054 |
2.7 |
2 |
0.1356 |
0.136 |
0.048 |
0.049 |
0.049 |
2.4 |
|
3 |
0.1376 |
0.1381 |
0.050 |
0.051 |
0.051 |
2.5 |
|
Test Item |
1 |
2.1997 |
2.1852 |
2.113 |
2.098 |
2.105 |
105.6 |
2 |
2.0212 |
1.998 |
1.934 |
1.911 |
1.922 |
96.4 |
|
3 |
2.1513 |
2.1515 |
2.064 |
2.064 |
2.064 |
103.5 |
Optical density and viability results II
Tissue-Type |
Substance |
Average OD |
SD (OD) |
Average % viability |
SD (viability) |
CV (%) |
viable |
Negative Control (DPBS) |
1.994 |
0.067 |
100.0 |
3.34 |
3.34 |
Positive Control (5% SDS) |
0.051 |
0.003 |
2.6 |
0.13 |
5.18 |
|
Test Item |
2.031 |
0.096 |
101.8 |
4.81 |
4.72 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In conclusion, in this study and under the experimental conditions reported, Chromium, iron, titanium and zinc spinel and rutile is non-irritant to skin and does not require classification and labelling for skin irritation or corrosivity according to UN GHS and EU CLP.
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