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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 corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2019-12-20 to 2020-02-13
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
- Version / remarks:
- adopted 18 June 2019
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)benzenesulfonamide
- Cas Number:
- 2437256-84-1
- Molecular formula:
- C25H21N3O5S2
- IUPAC Name:
- N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)benzenesulfonamide
Constituent 1
- Specific details on test material used for the study:
- - Name: N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)benzenesulfonamide
- Lot/batch no.: 2019001
- Purity: 98.78%
- Appearance/physical state: white crystalline powder
- Expiry Date: 2020-10-28
- Storage: at room temperature, protected from light
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
25 mg of the test item were applied directly atop the EpiDerm tissue using an application spoon avoiding compression of the test item. To ensure good contact with the skin the test item was moistened with 25 µL H2O. The test item was spread to match size of the tissue.
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Details on animal used as source of test system:
- Not applicable
- Justification for test system used:
- The EpiDerm Skin Model is a well-established organotypic, three-dimensional model of the human epidermis and is used for in vitro experiments since many years. It is known for its similarity to human skin.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm (TM) (MatTek)
- Tissue batch number(s): 30844
Epiderm Kit:
The EpiDerm tissues were provided as kits (e.g. EPI-200-SIT, MatTek), consisting of the following components relevant for this study:
- 1x sealed 24-well plate containing e.g. 24 reconstructed epidermis units (area: 0.63 cm²); each reconstructed epidermis is attached to a cell culture insert and maintained on nutritive agar for transport (Lot No.: 30844)
- 2x 24-well plates
- 4x 6-well plates
- 1x bottle of assay medium (DMEM-based medium, Lot No.: 011620MJB)
- 1x bottle of DPBS Rinse Solution (Lot No.: 112719ISE)
- 25 pieces Nylon Mesh circles (8 mm diameter, 200 µm pore)
FURTHER REAGENTS
- MTT stock solution: 5 mg/mL MTT (VWR; Lot 18I1156332) in PBS (Gibco; Lot No.: 2098592)
- MTT medium: MTT stock solution was diluted 1 + 4 with DMEM-based medium (final concentration 1 mg/mL)
- Isopropanol (AppliChem; Lot No.: 0001815947)
- Aqua dest. (Sigma Aldrich; Lot No.: RNBH8991 (pre-test), RNBG3520 (main test))
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 60 min exposure: 37 ± 1 °C; 3 min exposure: RT
- Temperature of post-treatment incubation (if applicable): 37 ± 1 °C (for 3 h, 5.0% CO2 / 95% air)
REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps:
At the end of exposure each tissue was rinsed about 20 times with PBS by filling and emptying the tissue insert. Excess liquid was carefully removed and transferred into new wells pre-filled with 0.3 mL/well pre-warmed MTT solution.
After 3 h MTT incubation tissues were rinsed twice in PBS and dried. Then the inserts were transferred into 12-well “extraction plates“. 2 mL of isopropanol were pipetted into each insert, thus the insert was covered from both sides. The extraction plates were sealed in zip-bags to inhibit isopropanol evaporation. Extraction was carried out either over night without shaking at room temperature or, alternatively, at least 2 h with shaking at room temperature.
After the extraction period the inserts were pierced with an injection needle to allow the extracts to run through the tissues into the corresponding wells. Then the inserts were discarded and the extraction plates were placed on a shaker for 15 min.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: MTT stock solution: 5 mg/mL MTT (VWR; Lot 18I1156332) in PBS (Gibco; Lot No.: 2098592); MTT medium: MTT stock solution was diluted 1 + 4 with DMEM-based medium (final concentration 1 mg/mL)
- Incubation time: 3 h min at 37 ± 1 °C
- Spectrophotometer: plate spectrophotometer
- Wavelength: 570 nm
NUMBER OF REPLICATE TISSUES: 2
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- To check the MTT-reducing capability of the test item, 25 mg of the test item were mixed per 1 mL MTT medium and incubated for 1 h at 37 ± 1 °C, 5.0% CO2 / 95% air. The mixture did not turn blue/purple. Thus, the additional test with freeze-killed tissues and the quantitative corrections were not necessary.
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%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied: 25 mg + 25 μL H2O
NEGATIVE CONTROL
- Amount(s) applied: 50 μL distilled water
- Lot/batch no.: RNBG3520, Sigma
POSITIVE CONTROL
- Amount(s) applied: 50 µl KOH
- Concentration: 8N
- Lot/batch no.: B1041112511, Merck - Duration of treatment / exposure:
- 3 min and 60 min
- Duration of post-treatment incubation (if applicable):
- 3 hours
- Number of replicates:
- two
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 minutes/mean of two replicates
- Value:
- 101.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 minutes/mean of two replicates
- Value:
- 76.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- For detailed results please refer to box "Any other information on results incl. tables".
OTHER EFFECTS:
Pre-experiments:
The mixture of 25 mg test item per 1 mL MTT medium showed no reduction of MTT as compared to the solvent. The mixture did not turn blue/purple. Therefore, NSMTT is determined to be 0%. The mixture of 25 mg test item per 300 µL Aqua dest. and per 90 µL isopropanol showed no colouring as compared to the solvent. Therefore, NSC is determined to be 0%. The test item showed no non-specific reduction of MTT and no relevant colouring potential after mixture with Aqua dest. and with isopropanol. Therefore, no additional controls for correction of possible false-negative results were necessary.
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: Acceptance Criteria
|
Value |
Cut off |
pass/fail |
Mean Absolute OD570 nm NC (3 min Experiment) |
1.708 |
0.8 ≤ NC ≤ 2.8 |
pass |
Mean Absolute OD570 nm NC (60 min Experiment) |
1.789 |
0.8 ≤ NC ≤ 2.8 |
pass |
Mean Relative Tissue Viability [%] of PC (60 min experiment) |
6.8 |
< 15% |
pass |
CV [%] (in the range of 20 – 100% viability) |
0.6 – 9.8 |
≤ 30% |
pass |
NC: negative control
PC: positive control
Table 2: Results of 3 min Experiment
Name |
Negative Control |
Positive Control |
Test Item |
|||
Replicate Tissue |
1 |
2 |
1 |
2 |
1 |
2 |
Absolute OD570 |
1.578 |
1.844 |
0.195 |
0.341 |
1.719 |
1.768 |
|
1.600 |
1.808 |
0.188 |
0.330 |
1.695 |
1.712 |
|
1.598 |
1.818 |
0.190 |
0.336 |
1.724 |
1.755 |
Mean Absolute OD570 |
1.708**** |
0.263 |
1.729 |
|||
OD570- Blank Corrected |
1.530 |
1.796 |
0.147 |
0.293 |
1.671 |
1.720 |
|
1.553 |
1.760 |
0.140 |
0.382 |
1.647 |
1.664 |
|
1.550 |
1.770 |
0.142 |
0.288 |
1.676 |
1.707 |
Mean OD570 of 3 Aliquots (Blank Corrected) |
1.544 |
1.775 |
0.143 |
0.288 |
1.665 |
1.697 |
SD OD570 of 3 Aliquots |
0.012 |
0.018 |
0.004 |
0.005 |
0.016 |
0.029 |
Total Mean OD570of 2 Replicate Tissues (Blank Corrected) |
1.660* |
0.215 |
1.681 |
|||
SD OD570 of 2 Replicate Tissues |
0.163 |
0.102 |
0.023 |
|||
Mean Relative Tissue Viability [%] |
100.0 |
13.0 |
101.3 |
|||
Coefficient Of Variation [%]*** |
9.8 |
47.5 |
1.4 |
* corrected mean OD570 of the negative control corresponds to 100% absolute tissue viability.
*** coefficient of variation (CV) (in the range of 20 – 100% viability) between two tissues treated identically is ≤ 30%.
****The mean absolute OD570 of the negative control is ≥ 0.8 and ≤ 2.8
Table 3: Results of 60 min Experiment
Name |
Negative Control |
Positive Control |
Test Item |
|||
Replicate Tissue |
1 |
2 |
1 |
2 |
1 |
2 |
Absolute OD570 |
1.786 |
1.789 |
0.168 |
0.163 |
1.475 |
1.317 |
|
1.797 |
1.800 |
0.170 |
0.168 |
1.442 |
1.335 |
|
1.806 |
1.757 |
0.165 |
0.160 |
1.421 |
1.315 |
Mean Absolute OD570 |
1.789**** |
0.166 |
1.384 |
|||
OD570- Blank Corrected |
1.738 |
1.741 |
0.120 |
0.115 |
1.427 |
1.269 |
|
1.750 |
1.752 |
0.123 |
0.120 |
1.394 |
1.287 |
|
1.759 |
1.709 |
0.117 |
0.112 |
1.373 |
1.268 |
Mean OD570 of 3 Aliquots (Blank Corrected) |
1.749 |
1.734 |
0.120 |
0.116 |
1.398 |
1.275 |
SD OD570 of 3 Aliquots |
0.010 |
0.023 |
0.003 |
0.004 |
0.027 |
0.011 |
Total Mean OD570 of 2 Replicate Tissues (Blank Corrected) |
1.741* |
0.118 |
1.337 |
|||
SD OD570 of 2 Replicate Tissues |
0.010 |
0.003 |
0.087 |
|||
Mean Relative Tissue Viability [%] |
100.0 |
6.8** |
76.7 |
|||
Coefficient Of Variation [%]*** |
0.6 |
2.5 |
6.5 |
* corrected mean OD570 of the negative control corresponds to 100% absolute tissue viability.
** mean relative tissue viability of the 60 min positive control < 15%
*** coefficient of variation (CV) (in the range of 20 – 100% viability) between two tissues treated identically is ≤ 30%.
**** The mean absolute OD570of the negative control is ≥ 0.8 and ≤ 2.8
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In conclusion, based on the results obtained from this in vitro skin corrosion study (OECD 431), the test item is considered to be non-corrosive (UN GHS Category 1B or 1C).
- Executive summary:
In an in vitro skin corrosion study conducted according to OECD guideline 431, the test item was applied topically to the EpiDermTM tissue for 3 min and 60 min followed by immediate determination of cytotoxic effects via MTT reduction assay.
Corrosivity potential of the test item was predicted from the relative mean tissue viabilities obtained after both treatment periods had been compared to the corresponding negative control tissues. The mean relative tissue viability (% negative control) was above 15% (76.7%) after 60 min treatment, and above 50% (101.3%) after 3 min treatment. The positive and negative controls confirmed the validity of the study. Based on the results, the test item can be considered as non-corrosive in conclusion with CLP Regulation 1272/2008.
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