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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 sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From May 18th to July 09th, 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
- Principles of method if other than guideline:
- Method described in the following papers:
1. Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin model. Development of the SENS-IS assay. Cottrez F., Boitel E., Auriault C., Aeby P., Groux H. Toxicology in vitro 29: 787-802, 2015.
2. SENS-IS, a 3D reconstituted epidermis based model for quantifying chemical sensitization potency: reproductibility and predictivity results from an inter-laboratory study. Cottrez F., Boitel E., Ourlin J.C., Peiffer J.L., Fabre I., Henaoui I.S., Mari B., Vallauri A., Paquet A., Barbry P., Auriault C., Aeby P., Groux H. . Toxicology in Vitro 32: 248-260, 2016. - GLP compliance:
- no
- Remarks:
- not fully validated method
- Type of study:
- other: activation of ARE and SENS-IS gene subset
- Justification for non-LLNA method:
- LLNA method was not carried out because the test substance is a complex metal
Test material
- Test material form:
- solid
Constituent 1
In vitro test system
- Details on the study design:
- Preliminary test: Solubility test
The solubility of the test item was assessed in phosphate buffered saline (PBS), olive oil (OO), and dimethylsulfoxide (DMSO) at a concentration of 10% and 50%, at room temperature and at 37°C.
The solubility of the test item was assessed by visual inspection of each preparation.
Main test: SENS-IS assay
The test item (30 µL) was deposited on the epidermis surface and gently spread on the entire surface [3]. After 15 minutes of exposure, the Episkin™ was rinsed with PBS and then incubated at 37°C for 6 hours.
After incubation, reconstructed epidermis was removed from the inserts with forceps and placed in a cryotube for freezing in liquid nitrogen. The epidermis was then transferred in a tube containing 1 mL of Qiazol reagent and 2 steel beads. Epidermis was homogenized using the TissueLyser II. After centrifugation, the supernatant was collected and stored at -20°C until RNA extraction.
After addition of bromochloropropane, total RNA were purified using the miRNeasy extraction Kit according to the manufacturer’s instructions (Qiagen, Courtaboeuf, France). RNA quality was assessed by measuring 260/280 absorbance ratio. The mRNA was then reversed as cDNA using SuperScript III Reverse Transcriptase kit and RNase inhibitor.
After reverse transcription, quantitative gene expression was measured by qRT-PCR using a SYBRGreen® buffer and specific primers defined for the SENS-IS test. The housekeeping genes (Glucuronidase ß, ß2 microglobuline, and Nono « non-POU domain containing octamer-binding ») were analyzed in parallel. - Vehicle / solvent control:
- DMSO
- Negative control:
- other: DMSO
- Positive control:
- other: SLS, 10%= Positive control for irritation and negative control for sensitization; TNBS, 1M= Positive control for sensitization
Results and discussion
- Positive control results:
- SLS at 5% was classified as irritant (number of overexpressed irritant genes > 15) and non-sensitizer, the number of overexpressed genes in both the SENS-IS and ARE groups being below 7.
TNBS at 1M was classified as sensitizer since more than 6 genes are overexpressed in at least one of the two groups of genes (SENS-IS or ARE).
In vitro / in chemico
Resultsopen allclose all
- Group:
- test chemical
- Run / experiment:
- run/experiment 2
- Parameter:
- other: Number of overexpressed SENS-IS and ARE genes
- Value:
- 2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Vehicle: 50% DMSO
- Group:
- test chemical
- Run / experiment:
- run/experiment 2
- Parameter:
- other: Number of overexpressed SENS-IS and ARE genes
- Value:
- 1
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Vehicle: 100% DMSO
- Group:
- test chemical
- Run / experiment:
- run/experiment 1
- Parameter:
- other: Number of overexpressed SENS-IS and ARE genes
- Value:
- 2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Vehicle: 10% PBS
- Group:
- test chemical
- Run / experiment:
- run/experiment 1
- Parameter:
- other: Number of overexpressed SENS-IS and ARE genes
- Value:
- 2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Vehicle: 1% DMSO
- Group:
- test chemical
- Run / experiment:
- run/experiment 1
- Parameter:
- other: Number of overexpressed SENS-IS and ARE genes
- Value:
- 2
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Vehicle: 10% DMSO
- Group:
- test chemical
- Run / experiment:
- run/experiment 1
- Parameter:
- other: Number of overexpressed SENS-IS and ARE genes
- Value:
- 3
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Vehicle: 50% DMSO
Any other information on results incl. tables
The test item was soluble at 10 and 50% (w/v) in PBS and in DMSO. It was not soluble at 10 and 50% (w/v) in olive oil.
Applicant's summary and conclusion
- Interpretation of results:
- other: No skin sensitising according to the classification criteria described in the SENS-IS assay
- Conclusions:
- not skin sensitising
- Executive summary:
Method: the substance has been tested for its potential to induce skin sensitisation according to the SENS-IS assay (Cottrez F. et al, Toxicology in vitro 29 (2015) 787 -802).
The objective of this study was to evaluate the capacity of the test item to induce the expression of specific irritation and sensitization biomarkers in a 3D-reconstructed epidermis model.
The results obtained for the positive and negative controls were within acceptance criteria defined in the Study Plan.
Considering the number of over-expressed genes in the “SENS-IS” and “ARE” gene groups, the test item gave negative result (less than 7 genes induced) when it was tested at 1, 10, 50 (w/v) in DMSO and at 10% (w/v) in PBS. Moreover, negative results were obtained when the test item was incubated at 100% (w/v) in DMSO.
In conclusion, under the experimental conditions of this SENS-IS assay, the test item can be classified as a non-sensitizer.
It should be mentioned that the SENS-IS method correlate more than 92% with LLNA in potency class prediction and should demonstrated a higher performance for predicting sensitization when combined with other sensitization tests (in chemico, in vitro and in silico).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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