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EC number: 210-498-3 | CAS number: 616-91-1
- 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:
- March 21, 2018 - June 22, 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 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- July 28, 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: ECVAM 2009, Performance Standards for In-Vitro Skin Irritation test Methods boased on Reconstructed Human Epidermis (RHE)
- Qualifier:
- according to guideline
- Guideline:
- other: SkinEthic Skin Irritation Test Standard Operating Procedure (SOP): Using the Reconstructed Human Epidermis (RHE) model, INVITTOX
- Version / remarks:
- Version 2.1, 2009
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Merck KGaA, Non-Clinical Safety, Frankfurter Strasse 250, 64293 Darmstadt, Germany
Test material
- Reference substance name:
- Acetylcysteine
- EC Number:
- 210-498-3
- EC Name:
- Acetylcysteine
- Cas Number:
- 616-91-1
- Molecular formula:
- C5H9NO3S
- IUPAC Name:
- N-acetylcysteine
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: SkinEthic RHE-model RHE/S/17 obtained from Episkin/SkinEthic Laboratories, Lyon, France
- Tissue batch number(s): 18-RHE-041 (1st run) , 18-RHE-068 (2nd run)
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
- Temperature of post-treatment incubation: 37°C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: gently rinsing with minimum volume of 25 mL DPBS using pipette
- Observable damage in the tissue due to washing: no
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours at 37°C
- Spectrophotometer: ELx800, BioTek Instruments GmbH
- Wavelength: 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: OD=1.3
- Barrier function: 4.6h
- Morphology: well differentiated epidermis consisting of basal, spinous, granular layers and a stratum corneum
- Contamination: no
- Reproducibility: yes
NUMBER OF REPLICATE TISSUES: 3
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 2
PREDICTION MODEL
- The test substance is considered as non-irritant to skin if the viability after exposure and post-treatment incubation is greater than 50 %. A test item is identified as requiring classification and labelling according to UN GHS (Category 2 or Category 1) if the mean percent tissue viability after exposure and post-treatment incubation is equal or greater than 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied: 16 mg per tissue
NEGATIVE CONTROL
- Amount(s) applied: 16 µL
POSITIVE CONTROL
- Amount(s) applied: 16 µL
- Concentration: 5% aqueous solution - Duration of treatment / exposure:
- 42 min
- Duration of post-treatment incubation (if applicable):
- 42 hours
- Number of replicates:
- 3
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1st run
- Value:
- 82.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- 100%
- Positive controls validity:
- valid
- Remarks:
- 3.6%
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 2nd run
- Value:
- 98.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- 100%
- Positive controls validity:
- valid
- Remarks:
- 6.7%
- 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:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes
Any other information on results incl. tables
Table 1: Results of the 1st Run
Group |
Tissue 1 |
Tissue 2 |
Tissue 3 |
Mean |
SD |
||||
|
OD |
viability |
OD |
viability |
OD |
viability |
OD |
viability |
viability |
Negative |
2.034 |
104.1% |
1.912 |
97.9% |
1.913 |
98.0% |
1.953 |
100.00 |
3.6% |
Positive |
0.031 |
1.6% |
0.028 |
1.4% |
0026 |
1.3% |
0.028 |
1.4% |
14.3% |
Test item |
1.661 |
85.0% |
1.646 |
84.3% |
1.537 |
787% |
1.615 |
82.7% |
4.2% |
Table 2: Results of the 2nd Run
Group |
Tissue 1 |
Tissue 2 |
Tissue 3 |
Mean |
SD |
||||
|
OD |
viability |
OD |
viability |
OD |
viability |
OD |
viability |
viability |
Negative |
1.794 |
107.7% |
1.607 |
96.5% |
1.594 |
95.7% |
1.665 |
100.00 |
6.7% |
Positive |
0.025 |
1.5% |
0.021 |
1.3% |
0.021 |
1.3% |
0.022 |
1.4% |
7.1% |
Test item |
1.562 |
93.8% |
1.581 |
95.0% |
1.798 |
108.0% |
1 647 |
98.9% |
8.0% |
Table 3: Acceptability of the Test (Run 1)
Acceptability of the Quality Control Data of the Skin Model with Reference to Historical |
||
|
Acceptance Criterion |
Result |
Negative control OD |
≥ 0.8 and ≤ 3.0 |
1.912 to 2.034 |
Acceptability of the Positive and Negative Control stated by Episkin/SkinEthic |
||
|
Acceptance Criterion |
Result |
Mean OD negative control |
≥1.2 |
1.953 |
Mean viability positive control |
< 40% |
1.4% |
SD of group-mean value |
≤18% |
14.3% (positive control) |
Acceptability of the Positive and Negative Control based on Historical Data of the Testing |
||
|
Acceptance Criterion |
Result |
Mean OD negative control |
≥1.453 |
1.953 |
Mean viability positive control |
≤ 2.89% |
1.4% |
Test Item Data Acceptance Criteria: |
||
|
Acceptance Criterion |
Result |
SD of group-mean value |
≤ 18% |
4.2% |
Table 4: Acceptability of the Test (Run 2)
Acceptability of the Quality Control Data of the Skin Model with Reference to Historical |
||
|
Acceptance Criterion |
Result |
Negative control OD |
≥ 0.8 and ≤ 3.0 |
1.594 to 1.794 |
Acceptability of the Positive and Negative Control stated by Episkin/SkinEthic |
||
|
Acceptance Criterion |
Result |
Mean OD negative control |
≥1.2 |
1.665 |
Mean viability positive control |
< 40% |
1.4% |
SD of group-mean value |
≤18% |
7.1% (positive control) |
Acceptability of the Positive and Negative Control based on Historical Data of the Testing |
||
|
Acceptance Criterion |
Result |
Mean OD negative control |
≥1.450 |
1.665 |
Mean viability positive control |
≤ 2.87% |
1.4% |
Test Item Data Acceptance Criteria: |
||
|
Acceptance Criterion |
Result |
SD of group-mean value |
≤ 18% |
8.0% |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of the study the substance is not considered to possess an irritant potential to skin (UN GHS: No Category).
- Executive summary:
A study according OECD TG 439 was conducted to investigate the potential of the test item to induce skin irritation in an in vitro human skin model (SkinEthic RHE-model).
The substance 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 irritation potential.Triplicates of the human skin RHE-model were treated with the test item, the negative or the positive control for 42 minutes (± 1 minute). 16 µL of either the negative control (DPBS-buffer) or the positive control (5% aqueous solution of sodium dodecyl sulfate) were applied to the tissues. Before application of 16 mg of the solid test item, 10 µL of deionised water was spread to the epidermis surface to improve the contact between the test item and the epidermis. Because of non-concordant replicate results after treatment with the substance between the first (non-valid) run and the second run, a third run was performed. Only the two valid runs performed are reported as run 1 and run 2. All acceptability criteria after treatment with the negative control (DPBS-buffer) and the positive control (5% aqueous solution of sodium dodecyl sulfate) were met. Following treatment with the test item, the tissue viability was 82.7% in run 1 and 98.9% in run 2 and thus, higher than 50% in both runs, i.e. according to OECD TG 439 the test item is considered as non-irritant to skin (UN GHS: No Category).
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