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EC number: 200-654-9 | CAS number: 67-47-0
- 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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 May 2019 - 08 August 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- 2012
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EpiSkin™ SOP, Version 1.8 (February 2009), ECVAM Skin Irritation Validation Study: Validation of the EpiSkin™ test method 15 min - 42 hours for the prediction of acute skin irritation of chemicals.
- Version / remarks:
- 2009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 67-47-0
- Molecular formula:
- C6H6O3
- Reference substance name:
- Fructose
- EC Number:
- 200-333-3
- EC Name:
- Fructose
- Cas Number:
- 57-48-7
- Molecular formula:
- C6H12O6
- IUPAC Name:
- D-fructose
- Reference substance name:
- 1-(furan-2-yl)-2-hydroxyethanone
- Cas Number:
- 17678-19-2
- Molecular formula:
- C6H6O3
- IUPAC Name:
- 1-(furan-2-yl)-2-hydroxyethanone
- Reference substance name:
- Water
- EC Number:
- 231-791-2
- EC Name:
- Water
- Cas Number:
- 7732-18-5
- Molecular formula:
- H2O
- IUPAC Name:
- water
- Reference substance name:
- Sodium formate
- EC Number:
- 205-488-0
- EC Name:
- Sodium formate
- Cas Number:
- 141-53-7
- Molecular formula:
- CH2O2.Na
- IUPAC Name:
- sodium formate
- Reference substance name:
- Sodium nitrate
- EC Number:
- 231-554-3
- EC Name:
- Sodium nitrate
- Cas Number:
- 7631-99-4
- Molecular formula:
- HNO3.Na
- IUPAC Name:
- sodium nitrate
- Reference substance name:
- Glucose
- EC Number:
- 200-075-1
- EC Name:
- Glucose
- Cas Number:
- 50-99-7
- Molecular formula:
- C6H12O6
- IUPAC Name:
- D-glucose
- Reference substance name:
- Sodium acetate
- EC Number:
- 204-823-8
- EC Name:
- Sodium acetate
- Cas Number:
- 127-09-3
- Molecular formula:
- C2H4O2.Na
- IUPAC Name:
- sodium acetate
- Reference substance name:
- 2-furaldehyde
- EC Number:
- 202-627-7
- EC Name:
- 2-furaldehyde
- Cas Number:
- 98-01-1
- Molecular formula:
- C5H4O2
- IUPAC Name:
- 2-furaldehyde
- Reference substance name:
- Sodium 4-oxovalerate
- EC Number:
- 243-378-4
- EC Name:
- Sodium 4-oxovalerate
- Cas Number:
- 19856-23-6
- Molecular formula:
- C5H8O3.Na
- IUPAC Name:
- sodium 4-oxopentanoate
- Reference substance name:
- Formaldehyde
- EC Number:
- 200-001-8
- EC Name:
- Formaldehyde
- Cas Number:
- 50-00-0
- Molecular formula:
- CH2O
- IUPAC Name:
- formaldehyde
- Test material form:
- solid: crystalline
- Details on test material:
- freeze-dried material
Batch: 1808A-RO-C-I1-FD-Chg#3
Appearance Crystal / brown
Storage: Refrigerator (2 - 8 °C)
Expiring date: 31 December 2019
Constituent 1
impurity 1
impurity 2
impurity 3
impurity 4
impurity 5
impurity 6
impurity 7
impurity 8
impurity 9
impurity 10
- Specific details on test material used for the study:
- - Batch No.: 1808A-RO-C-I1-FD-Chg#3
- Storage Conditions: 2-8°C
In vitro test system
- Test system:
- human skin model
- Remarks:
- EpiSkin Small Model (three-dimensional human epidermis model) manufactured by EPISKIN SNC Lyon, France
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- The EpiSkin Model has been validated for irritation testing in an international trial. The EpiSkin method is a reliable and relevant stand-alone test for predicting rabbit skin irritation, when the endpoint is evaluated by MTT reduction and for being used as a replacement for the Draize Skin Irritation test (OECD TG 404) for the purposes of distinguishing between skin irritating and no-skin irritating test substances.
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- epidermal surface was first moistened with 5 µL deionised water
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiSkinTM Small Model
- Supplier: SKINETHIC Laboratories 4, rue Alexander Fleming, 69366 Lyon Cedex 07 - France
- Tissue batch number: 19-EKIN-019
- Expiry date: 13 May 2019
- Date of initiation of testing: 08 May 2019
PRE-INCUBATION
The “maintenance medium” was pre-warmed to 37°C. The appropriate number of an assay plate wells were filled with the pre-warmed medium (2 mL per well). The epidermis units were placed with the media below them, in contact with the epidermis into each prepared well and then incubated over night at 37°C in an incubator with 5 % CO2, >= 95% humidified atmosphere.
EXPOSURE (DAY 0)
- Test Item: The epidermal surface was first moistened with 5 µL deionised water (prepared by MILLIPORE Synergy UV HF ASTM 1: F8JA80461C in Toxi-Coop ZRT) in order to improve further contact between the test item and epidermis. Subsequently, 10 mg of the test item was applied evenly to the epidermal surface. The test item was spread gently with a curved flat spatula in order to cover evenly all the skin surface if necessary.
- Positive and negative control: A volume of 10 µL positive control (SDS 5 % aq.) or negative control (1x PBS) was applied on the skin surface by using a suitable pipette. Chemicals were gently spread with the pipette tip in order to cover evenly all the epidermal surface if necessary.
The plates with the treated epidermis units were incubated for the exposure time of 15 minutes (± 0.5 min) at room temperature.
NUMBER OF REPLICATE TISSUES FOR TEST ITEMS AND CONTROLS
Triplicates
REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps: 25 mL PBS 1x solution, once. rest of the PBS was removed from the epidermal surface with suitable pipette tip linked to a vacuum source
- Observable damage in the tissue due to washing: none
POST-INCUBATION (DAY 0-2)
After rinsing the units were placed into the plate wells with fresh pre-warmed “maintenance medium” (2 mL/well) below them and then incubated for 42 hours (± 1h) at 37°C in an incubator with 5 % CO2, >=95% humidified atmosphere.
MTT TEST (DAY 2)
After the 42 hours incubation the EpiSkinTMSM units were transferred into the MTT solution filled wells (2 mL of 0.3 mg/mL MTT per well) and then incubated for 3 hours (± 5 min) at 37°C in an incubator with 5±1 % CO2 protected from light, >=95% humidified atmosphere.
FORMAZAN EXTRACTION (DAY 2)
A disk of epidermis was cut from the unit (this involves the maximum area of the disk) using a biopsy punch (supplied as part of the kit). The epidermis was separated with the aid of forceps and both parts (epidermis and collagen matrix) were placed into a tube of 500 µL acidified isopropanol (one tube corresponding to one well of the tissue culture plate).
The capped tubes were thoroughly mixed by using a vortex mixer to achieve a good contact of all of the material with the acidified isopropanol then incubated for approximately four hours at room temperature protected from light with gentle agitation (~150 rpm) for formazan extraction. At the middle and at the end of the incubation period, each tube was additionally mixed using a vortex mixer to help extraction.
CELL VIABILITY MEASUREMENTS (DAY 2)
Following the formazan extraction, 2×200 µL sample from each tube was placed into the wells of a 96-well plate (labelled appropriately) and read the OD (Absorbance / Optical Density) of the samples in a 96-well plate spectrophotometer (Thermo Scientific; Multiscan FC) at 570 nm (±10 nm; Read out range: 0-3.5 Abs, Linearity range: 0.2136 – 3.1752) using acidified isopropanol solution as the blank (6×200 µL).
PREDICTION MODEL / DECISION CRITERIA
The test chemical is identified as requiring classification and labelling according to UN GHS (Category 2 or Category 1), if the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal to 50% of the negative control. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 10 mg of the test item.
POSITIVE AND NEGATIVE CONTROL
- Amounts applied: A volume of 10 µL positive or negative control. - Duration of treatment / exposure:
- 15 ± 0.5 min
- Duration of post-treatment incubation (if applicable):
- 42 ± 1h
- Number of replicates:
- Three replicates were used for the test item and controls, respectively.
Results and discussion
In vitro
Results
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1
- Value:
- 72
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: mean corrected value
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Possible direct MTT reduction with test item: As the test item has an intrinsic colour (brown), the check-method for possible direct MTT reduction with test item was not completed for the following reason: The color of the MTT solution was close to black after it was mixed with test item. So the interaction of the test item with MTT solution could not be determined. Based on this information the additional controls were automatically used. This step prevents the false viability which is the possible interaction with MTT, and it occurs if the test item cannot be removed totally from the surface of the tissues. In this situation the direct interaction with MTT was defined based on the OD results of additional controls.
The non-specific MTT reduction (NSMTT) was determined to be 5.329 %. As the NSMTT were below 50 % the true MTT metabolic conversion in all occasions and the correction of viability percentages were undertaken.
- Colouring potential of test item: The test item has an intrinsic colour (brown). If the test item is not white, off withe, almost white and/or colorless the additional controls are automatically used and based on the OD results of additional controls the Non Specific Colour % (NSCliving %) is determined. This step prevents the false viability, which can possibly be caused by the stained surface of the tissues by the test item. Two additional test item-treated tissues were used for the non-specific OD evaluation.
Mean OD (measured at 570 nm) of these tissues was determined as 0.040. The Non Specific Colourliving % (NSCliving %) was calculated as 4.8 %. As the NSCliving is below 5%, true MTT metabolic conversion for colour interference is not undertaken.
ACCPETANCE OF RESULTS
- Acceptance criteria met for negative control: Mean OD value 0.834 and standard deviation value (SD) for the % viability 0.43 (The mean OD value of the three negative control tissues should be between 0.6 and 1.5 and the standard deviation value (SD) of the % viability should be = or < 18)
- Acceptance criteria met for positive control: 20% mean viability range standard deviation value (SD) for the % viability 7.27 (The acceptable mean percentage viability range for positive controls is 0-40% and the standard deviation value (SD) of the % viability should be = or < 18.)
- For test chemicals, the standard deviation value (SD) of the % viability should be = or < 18 : 6.57 % SD
Any other information on results incl. tables
OD values and viability percentages of the controls:
Control | Optical Density (OD) | Viability (%) | |
Negative Control 1X PBS |
1 | 0.0831 | 100 |
2 | 0.0833 | 100 | |
3 | 0.0838 | 100 | |
mean | 0.0834 | 100 | |
standard deviation (SD) | 0.43 | ||
Positive Control SDS (5% aq.) |
1 | 0.136 | 16 |
2 | 0.136 | 16 | |
3 | 0.241 | 29 | |
mean | 0.171 | 20 | |
standard deviation (SD) | 7.27 |
OD values and viability percentages of the test item (including corrected values):
Test Item | Optical Density (OD) | TODTT | Viability (%) | realtive Viability (%) | |
5-(Hydroxymethyl) furfural |
1 | 0.668 | 0.623 | 80 | 75 |
2 | 0.581 | 0.536 | 70 | 64 | |
3 | 0.682 | 0.637 | 82 | 76 | |
mean | 0.643 | 0.599 | 77 | 72 | |
standard deviation (SD) | 6.57 | 6.57 |
OD values of additional controls for MTT-interacting test item:
Additional controls | Optical Density (OD) | |
Negative control killed tissues: 1x PBS |
1 2 3 mean |
0.061 0.095 0.066 0.074 |
Test item treated killed tissues: 5-(Hydroxymethyl)furfural |
1 2 3 mean |
0.145 0.099 0.111 0.118 |
OD values and NSC % of additional control:
Additional colour control | Optical Density (OD) | Non Specific Colour % (NSCliving %) | |
5-(Hydroxymethyl)furfural (test item treated tissues without MTT incubation) |
1 2 mean |
0.037 0.043 0.040 |
4.8 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The results obtained from this in vitro skin irritation test, using the EPISKIN model, indicated that the test item reveals no skin irritation potential under the utilised testing conditions. The test item 5-(Hydroxymethyl)furfural is considered to be non-irritant to skin and is therefore not classified (UN GHS No Category).
- Executive summary:
EpiSkinTMSM test of 5-(Hydroxymethyl)furfural has been performed to predict its irritation potential by measurement of its cytotoxic effect, as reflected in the MTT assay, according to the OECD Test Guideline No. 439,28 July 2015.
Disks of EPISKIN (three units) were treated with test item and incubated for 15 minutes (± 0.5 min) at room temperature. Exposure of test material was terminated by rinsing with PBS 1x solution. Epidermis units were then incubated at 37±1 °C for 42 hours (± 1 h) in an incubator with 5±1 % CO2,=95 % humidified atmosphere. The viability of each disk was assessed by incubating the tissues for 3 hours (± 5 min) with MTT solution at 37±1 °C in 5±1 % CO2protected from light. The precipitated formazan was then extracted using acidified isopropanol and quantified spectrophotometrically.
SDS (5 % aq.) and 1×PBS treated (three units / positive and negative control) epidermis were used as positive and negative controls respectively. For each treated tissue viability was expressed as a percentage relative to negative control.
The test item has an intrinsic colour (brown), therefore two additional test item treated tissues were used for the non-specific OD evaluation (NSCliving).
The test item is a possible MTT-reducer, therefore additional controls (test item treated killed tissues and negative control treated killed tissues) were used to detect and correct for test substance interference with the viability measurement.
The test item is a possible MTT-reducer and has an intrinsic colour (brown). To avoid a possible double correction [TODTT (MTT and NSCliving)] for colour interference, a third control for non-specific colour in killed tissues (NSCkilled) was performed.
The test chemical is identified as requiring classification and labelling according to UN GHS (Category 2 or Category 1), if the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (=) to 50 % of the negative control.As the NSClivingis below 5%, true MTT metabolic conversion for colour interference is not undertaken.
In thisin vitroskin irritation test using the EPISKIN model, the test item 5-(Hydroxymethyl)furfural did not show significantly reduced cell viability in comparison to the negative control (mean corrected value for possible MTT reduction: 72 %). All obtained test item viability results were far above 50 % when compared to the viability values obtained from the negative control. Therefore the test item was considered to be non-irritant to skin.
Positive and negative controls showed the expected OD and cell viability values within acceptable limits and standard deviation of all calculated viability values (positive and negative control, test item) was below 18. The experiment was considered to be valid.
The results obtained from thisin vitroskin irritation test, using the EPISKIN model, indicated that the test item reveals no skin irritation potential under the utilised testing conditions. The test item 5-(Hydroxymethyl)furfural is considered to be non-irritant to skin and is therefore not classified (UN GHS No Category).
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