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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:
- 21 MAY 2021 - 20 JUL 2021
- 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 guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- 26 June 2020
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- Commission Regulation (EU) No 2019/1390 of 31 July 2019 amending, for the purpose of its adaptation to technical progress, the Annex to Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate
- Cas Number:
- 2311845-49-3
- Molecular formula:
- C33H42N4O3S4
- IUPAC Name:
- bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate
- Test material form:
- solid: particulate/powder
Constituent 1
In vitro test system
- Test system:
- human skin model
- Remarks:
- EpiSkinTM Small Model (EpiSkinTMSM)
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: three-dimensional human skin model comprising a reconstructed epidermis with a functional stratum corneum
- Justification for test system used:
- The EPISKIN model has been validated for irritation testing in an international trial. After a review of scientific reports and peer reviewed publications on the EPISKIN method, it showed evidence of being 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 and Method B.4 of Annex V to Directive 67/548/EEC) for the purposes of distinguishing between skin irritating and no-skin irritating test substances (STATEMENT ON THE VALIDITY OF IN-VITRO TESTS FOR SKIN IRRITATION; ECVAM; Institute for Health & Consumer Protection; Joint Research Centre; European Commission; Ispra; 27 April 2007).
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- The test item was applied in its original form, no formulation was required.
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiSkinTM Small Model (EpiSkinTMSM)
- Tissue batch number(s): 21-EKIN-022
- Expiry date: 07 June 2021
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: at room temperature (22.9-23.7 °C).
- Temperature of post-treatment incubation (if applicable): The epidermis units were placed with the media below them, in contact with the epidermis into each prepared well and then incubated overnight (18-24h) at 37±1 °C in an incubator with 5±1 % CO2, ≥95 % humidified atmosphere.
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: After the incubation time the EpiSkinTMSM units were removed and rinsed thoroughly with approximately 25 mL/each tissue 1x PBS solution to remove all of the test material from the epidermal surface. The rest of the 1x PBS was removed from the epidermal surface with suitable pipette tip linked to a vacuum source (care was taken to avoid damage of epidermis).
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: The MTT stock solution was diluted with pre-warmed (37 °C) “assay medium” to a final concentration of 0.3 mg/mL.
- Incubation time: After the 42 hours (± 1h) 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±1°C in an incubator with 5±1 % CO2 protected from light, ≥95% humidified atmosphere.
- Spectrophotometer: Varioskan™ LUX Type 3020
- Wavelength: 200 – 1000 nm
NUMBER OF REPLICATE TISSUES: 3
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
Approximately 10 mg test item was added to 2 mL MTT 0.3 mg/mL solution and mixed. The mixture was incubated for three hours at 37±1 °C in an incubator with 5±1 % CO2, ≥ 95 % humidified atmosphere, protected from light and then any colour change observed (unaided eye assessment):
- Test items which do not interact with MTT: yellow
- Test items interacting with MTT: blue or purple
If the MTT solution colour becomes blue or purple, the test item interacts with the MTT. It is then necessary to evaluate the part of optical density (OD) due to the non-specific reduction of the MTT (i.e. by using killed epidermis).
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:
3 replicate of negative control, positive control and test item.
PREDICTION MODEL / DECISION CRITERIA
-In case the test chemical is found to be non-corrosive, and the tissue viability after exposure and post-treatment incubation is less than or equal (≤) to 50 %, the test item is considered to be irritant to skin in accordance with UN GHS Category 2. The test item may be considered as non-irritant to skin in accordance with UN GHS No Category if the tissue viability after exposure and post-treatment incubation is more than (>) 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The epidermal surface was first moistened with 5 μL deionised water in order to improve further contact between powder and epidermis. Subsequently, 10 mg of the test item was applied evenly to the epidermal surface
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): A volume of 10 μL negative control (1x PBS)
POSITIVE CONTROL
- Amount(s) applied (volume or weight): A volume of 10 μL positive control (SDS 5 % aq.)
Additional control for dyes and chemicals able to colour the tissue:
In addition to the normal procedure, two additional test item-treated tissues were used for the non-specific OD evaluation (NSCliving). - Duration of treatment / exposure:
- exposure time of 15 minutes (± 0.5 min)
- Duration of post-treatment incubation (if applicable):
- 42 hours (± 1h) incubation
- Number of replicates:
- Three replicates were used for the test item and positive and negative controls, respectively. Furthermore, two replicates were used for the additional control.
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1/ replicate 1
- Value:
- 101
- 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:
- 1/ replicate 2
- Value:
- 90
- 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:
- 1/ replicate 3
- Value:
- 91
- 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:
- mean
- Value:
- 94
- 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:
- - OTHER EFFECTS:
- Direct-MTT reduction: Colour change was not observed after three hours of incubation. Therefore, the test item was considered not to interact with the MTT, and additional controls and data calculations were not necessary. A false estimation of viability can be precluded.
- Colour interference with MTT: The test item showed no ability to become coloured in contact with water. The intrinsic colour of the test item is white and therefore considered not to be able to significantly stain the tissues and lead to a false estimate of viability. However, a white milky suspension was observed after the test item was mixed with isopropanol, so the test item showed interaction with isopropanol. Based on this information, 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 0.012. The Non Specific Colourliving % (NSCliving %) was calculated as 1 % (below 5 %). Therefore, additional data calculation was not necessary. A false estimation of viability can be precluded.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes. 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 ≤ 18.
- Acceptance criteria met for positive control: Yes. The acceptable mean percentage viability for positive controls is < 40% and the standard deviation value (SD) of the % viability should be ≤ 18.
- Acceptance criteria met for variability between replicate measurements: Yes. For test chemicals (test item and controls), the standard deviation value (SD) of the % viability should be ≤ 18.
The mean OD value of the three negative control tissues was 1.310. The mean OD value obtained for the positive control was 0.059 and this result corresponds to 4 % viability when compared to the results obtained from the negative control. Each calculated standard deviation value (SD) for the % viability was below 18. All validity criteria were within acceptable limits and therefore the study can be considered as valid.
Applicant's summary and conclusion
- Interpretation of results:
- other: EU GHS criteria not met
- Conclusions:
- The test item did not show significantly reduced cell viability in comparison to the negative control (mean relative value: 94 %). All obtained test item viability results were far above 50 % when compared to the viability values obtained from the negative control.
Therefore, from this in vitro skin irritation test, using the EPISKIN model, indicate that the test item reveals no skin irritation potential under the utilised testing conditions. The test item is considered to be non-irritant to skin and is therefore not classified (UN GHS No Category). - Executive summary:
The In Vitro Skin Irritation test was performed to predict its irritation potential by measurement of its cytotoxic effect, as reflected in the MTT assay, according to the OECD guideline 439 and under GLP compliance.
Disks of EPISKIN (three units) were treated with the test item and incubated for 15 minutes (± 0.5 min) at room temperature. Exposure to the test material was terminated by rinsing with 1x PBS 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 % CO2, ≥95 % humidified atmosphere, protected from light. The precipitated formazan was then extracted using acidified isopropanol and quantified spectrophotometrically.
SDS (5 % aq.) and 1×PBS treated epidermis (three units / positive and negative control) 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 did not show significantly reduced cell viability in comparison to the negative control (mean relative value: 94 %). 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. Standard deviation of all calculated viability values (test item and controls) was below 18. The experiment was considered to be valid.The results obtained from this in vitro skin irritation test, using the EPISKIN model, indicate that the test item reveals no skin irritation potential under the utilised testing conditions. The test item is considered to be non-irritant to skin and is therefore not classified (UN GHS No Category).
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