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EC number: 204-599-1 | CAS number: 123-08-0
- 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 corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- May 2, 2018 - June 28, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
- Version / remarks:
- July 29, 2016
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006. B.40.bis. In vitro skin corrosion: human skin model test
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: INVITTOX Protocol SkinEthic Skin Corrosivity Test, April 2012.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 4-hydroxybenzaldehyde
- EC Number:
- 204-599-1
- EC Name:
- 4-hydroxybenzaldehyde
- Cas Number:
- 123-08-0
- Molecular formula:
- C7H6O2
- IUPAC Name:
- 4-hydroxybenzaldehyde
- Test material form:
- solid
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- foreskin from a single donor
- Justification for test system used:
- The reconstituted human epidermis (RHE)-model is a three-dimensional human skin model and is histologically comparable to the in vivo human tissue. It consists of a main basal, supra basal, spinous and granular layer and a functional stratum corneum. The RHE-model is an accepted in vitro alternative model for skin corrosion testing. It involves topical application of test item to the surface of the epidermis and the subsequent assessment of the effects on cell viability. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiSkin/SkinEthic Laboratories, Lyon, France
- Tissue batch number(s): 18-RHE-060
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: At the end of the exposure periods, the test item, positive and negative control was removed immediately by gently rinsing with a minimum volume of 20 mL DPBS using a pipette. Excess DPBS was removed by gently shaking the tissue inserts and blotting the bottom of the tissue inserts with blotting paper.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours ± 15 min
- Spectrophotometer: ELx800, BioTek Instruments GmbH, Bad Friedenshall, Germany
- Wavelength: 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: OD 1.2 (CV =7.5%)
- Barrier function: 4.9 h
- Morphology: 5 cell layers, absence of significant histological abnormalities, well differentiated epidermis consisting of basal, spinous, granular layers and a stratum corneum
- Contamination: no
NUMBER OF REPLICATE TISSUES: 2
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.
Acceptability of the Quality Control Data of the Skin Model with Reference to Historical Batch Data:
The negative control OD values for the SkinEthic RHE-model have to be in the range of ≥ 0.8 and ≤ 3.0 at 570 nm as given in OECD Guideline 431.
Acceptance Criteria stated by Episkin/SkinEthic Laboratories:
Negative control acceptance criteria: The negative control data meet the acceptance criteria if the mean OD value of the 2 tissues is≥ 0.8 and ≤ 3.0 at 570 nm.
Positive control acceptance criteria: The positive control data meet the acceptance criteria if it classified as corrosive (% viability < 15% after 1 hour exposure).
Test substance data acceptance criteria: The range between identically treated tissues has to be less than 30%, with the exception of cases with OD ≤ 0.3 and for viabilities out the range 20 – 100%.
Acceptability of the Positive and Negative Control based on Historical Data of the Testing Laboratory:
The positive control data meet the acceptance criteria if the mean viability value, expressed as % of the negative control, is lower than or equal to a historically established boundary. The boundary is three standard deviations above the current historical mean (0.94%). The negative control data meet the acceptance criteria if the mean OD value is higher or equal than a historically established boundary at 570 nm. The boundary is two standard deviations below the current historical mean (3 minutes exposure: 1.596; 1 hour exposure: 1.467).
Negative Control, Positive Control and Test Substance Data Acceptance Criteria stated by the Testing Laboratory:
The range between identically treated tissues has to be less than 30%, with the exception of cases with OD ≤ 0.3 and for viabilities out the range 20 – 100%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied: 20 mg ± 3 mg of solid test material
Before adding 20 ± 3 mg of the test item, 20 ± 2 µL of deionised water was spread to the epidermis surface to improve further contact between the test item and the epidermis.
NEGATIVE CONTROL
- Amount(s) applied: 40 µL ± 3 µL (deionised water )
POSITIVE CONTROL
- Amount(s) applied: 40 µL ± 3 µL
- Concentration: An 8N potassium hydroxide solution dissolved deionised water pure - Duration of treatment / exposure:
- 3 min & 1 hour
- Number of replicates:
- 2
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Experiment 1 / 3 min
- Value:
- 100.4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Experiment 1 / 1 hour
- Value:
- 23.5
- 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: none
- Direct-MTT reduction: none
- Colour interference with MTT: none
ACCEPTANCE OF RESULTS:
Acceptability of the Quality Control Data of the Skin Model with Reference to Historical Batch Data:
Acceptance Criterion Result
Negative control OD ≥ 0.8 and ≤ 3.0 1.563 to 1.703
Acceptability of the Positive and Negative Control stated by Episkin/SkinEthic Laboratories:
Acceptance Criterion Result
Mean OD negative control ≥ 0.8 and ≤ 3.0 1.694 (3 min)
1.608 (1 hour)
Mean viability positive control < 15% after 1-hour exposure 0.9%
Range between identically treated < 30% 1.4% (3 min)
tissues with test item 17.6% (1 hour)
Acceptability of the Positive and Negative Control based on Historical Data of the Testing Laboratory:
Acceptance Criterion Result
Mean OD negative control ≥ 1.596 (3 min) 1.694 (3 min)
≥ 1.467 (1 hour) 1.608 (1 hour)
Mean viability positive control ≤ 0.94% 0.9%
Negative Control, Positive Control and Test Substance Data Acceptance Criteria stated by the Testing Laboratory:
Group Acceptance Criterion Result
Range between identically Negative control < 30% 1.0% (3 min)
treated tissues 5.8% (1 hour)
Positive control < 30% 83.3% (1 hour)
Test substance < 30% 1.4% (3 min)
17.6% (1 hour)
The range between identically treated tissues with the positive control was higher than 30% after 1 hour exposure (83.3%), but the optical densities measured were <0.3.
The study met all acceptance criteria.
Any other information on results incl. tables
Table 1: Results
Group | Time / [min] | Mean OD | Mean Relative viability / [%] |
Negative Control | 3 | 1.694 | 100.0 |
Negative Control | 60 | 1.608 |
100.0 |
Positive Control |
60 |
0.014 |
0.9 |
Test Material | 3 | 1.701 | 100.4 |
Test Material | 60 | 0.379 | 23.5 |
Table 2: Historical Data
Positive Control | Negative Control 3min | Negative Control 1 hours | |||
Mean Viability [%] | 0.58 | Mean Absorption [OD570] | 1.898 | Mean Absorption [OD570] | 1.963 |
Standard Deviation [%] | 0.12 | Standard Deviation |
0.151 |
Standard Deviation |
0.248 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- This study was performed according to GLP and the methods applied are fully compliant with OECD TG 431. Under the conditions of the present study, the test item is not considered to possess a corrosive potential to skin.
- Executive summary:
A study according OECD TG 431 was conducted to investigate the potential of the test item to induce skin corrosion in an in vitro human skin model. The test item was applied topically to a human reconstructed skin model followed by determination of the cell viability. Cell viability was determined by enzymatic conversion of vital dye MTT into a blue formazan salt and measurement of the formazan salt after extraction from tissues. The percent reduction of cell viability in comparison to untreated negative controls was used to predict the skin corrosion potential. Duplicates of the human skin RHE-model were treated with the test item or the negative control for 3 minutes and additional 1 hour. Duplicates with the positive control were only treated for 1 hour. 40 ± 3 µL of either the negative control (deionised water) or the positive control (potassium hydroxide, 8N) were applied to the tissues. Before application of 20 ± 3 mg of the solid test item, 20 ± 2 µL of deionised water was spread to the epidermis surface to improve the contact between the test item and the epidermis. After treatment with the positive control (potassium hydroxide, 8N) the mean viability value was 0.9% and, thus, lower than the historically established threshold of 0.94%. After treatment with the negative control (deionised water) the mean ODs were 1.694 (3 minutes exposure) and 1.608 (1 hour exposure) and, thus, higher than the historically established thresholds of 1.596 and 1.467, respectively. Thus, the acceptance criteria were met. Following treatment with the test item, the tissue viability was ≥50% after 3 minutes exposure (mean viability: 100.4%) and ≥15% after 1 hour exposure (mean viability: 23.5%), i.e. according to OECD 431 the test item is not considered as corrosive to skin.
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