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EC number: 242-440-8 | CAS number: 18599-22-9
- 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:
- 10 March 2020 to 13 March 2020
- 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 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
- Version / remarks:
- 25 June 2018
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- activation of keratinocytes
- Justification for non-LLNA method:
- Non animal test method -OECD approved. Activation of keratinocytes by the Induction of Antioxidant Response-Element Dependent Gene Activity and Cytotoxicity (Using MTT) in the Keratinocyte ARE Reporter Cell Line provides an in vitro procedure used for supporting the discrimination between skin sensitizers and non sensitizers in accordance with the UN GHS. According to REACH, in vivo methods can only be used if the in chemico or in vitro test methods are not adequate for the substance or cannot be used for classification and risk assessment.
Test material
- Reference substance name:
- 4-bromo-3,3,4,4-tetrafluorobut-1-ene
- EC Number:
- 242-440-8
- EC Name:
- 4-bromo-3,3,4,4-tetrafluorobut-1-ene
- Cas Number:
- 18599-22-9
- Molecular formula:
- C4H3BrF4
- IUPAC Name:
- 4-bromo-3,3,4,4-tetrafluorobut-1-ene
- Test material form:
- liquid
Constituent 1
In vitro test system
- Details on the study design:
- The Induction of Antioxidant-Response-Element Dependent Gene Activity and Cytotoxicity (Using
MTT) in the Keratinocyte ARE-Reporter Cell Line KeratinoSens™ skin sensitization assay is a highthroughput cell based in vitro test to screen for the skin sensitization potential of chemicals. The KeratinoSens™ cells (Givaudan, Switzerland) were propagated as a reporter cell line. The KeratinoSens™ cells are transfected HaCaT keratinocytes that include a 56-base-pair insertion containing the ARE sequence from the AKR1C2 gene, a SV40 promoter, the luciferase gene in the vector pGL4 from Promega, and a stable insertion allowing for cells to be selected in the presence of Geneticin (G418). The signalling pathway with the repressor protein Keap1 and the transcription factor Nrf2, which binds to the antioxidant / electrophile response element (ARE / EpRE), was shown to be a valuable cellular endpoint to detect skin sensitizers in vitro. The induction of luciferase directly indicates the activation of ARE dependent genes. Cytotoxicity of a test article was assessed using MTT (3-[4,5 - dimethylthiazol-2-yl] - 2,5 - diphenyl tetrazolium bromide). Cytotoxicity was determined by measuring the relative conversion of MTT in test article-treated cultures compared to the solvent control at 570nm absorbance.
Experimental Design
The experimental design of this study consisted of three definitive assays, two of which were valid and used, to determine the maximal induction (Imax), the concentration for maximal gene induction (CImax), the EC1.5 value (concen tration for a statistically significant induction of 50% above solvent controls), and a mean IC50 (concentration leading to 50% viability as compared to solvent controls) for the test article. For each definitive assay, the KeratinoSens™ cells were cultured in quadruplicate plates for approximately 24 hours, treated with the test article for 48±1 hours, and assessed for luciferase induction (3 plates) and cytotoxicity (1 plate).The procedures that were performed in this assay were a modification of the procedures previously described by Natsch, et al. (2008) and were performed similar to those procedures performed by the Institute for In Vitro Sciences, Inc. in the KeratinoSens™ ring-study. The BTFB Induction of Antioxidant Response Element-Dependent Gene Activity and Cytotoxicity (Using M TT) in the Keratinocyte ARE-Reporter Cell Line KeratinoSens™ Assay was performed to determine the skin sensitization potential of the test article, supplied by The Chemours Company. The laboratory phase of this study was conducted from 10 March 2020 to 13 March 2020 at the Institute for In Vitro Sciences, Inc. (IIVS).
Evaluation of Test Results
A test article was predicted to have sensitization potential if:1) The EC1.5 value fell below 1000 μM in at least 2 repetitions; 2) At the lowest concentration with a gene induction above 1.5, cellular viability was greater than 70%; and 3) There was apparent overall dose response which was similar between repetitions.
Results and discussion
- Positive control results:
- The positive control cinnamic aldehyde had a mean EC 1.5 of 9.08 μM and mean IC50 of >64 μM.
In vitro / in chemico
Results
- Key result
- Run / experiment:
- other: Mean of 2 definitive runs
- Parameter:
- other: Gene fold induction above the solvent control. There was no induction above 1.5 and viability was greater than 70%.
- Value:
- 0
- Vehicle controls validity:
- valid
- Negative controls validity:
- other: N/A see vehicle controls
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- The value of "0" is incorrect. The EC1.5 for test article BTFB was not determinable. There was no gene induction above 1.5-fold.
- Other effects / acceptance of results:
- Criteria for Determination of a Valid Definitive Assay The KeratinoSens™ assay was accepted when the positive control (cinnamic aldehyde) caused an EC1.5 value that fell within two standard deviations of the historical mean. Additionally, the results of the three definitive trials for each plate were assessed using similar criteria outlined in the validation ring trial . Those acceptance criteria included: 1) variability in DMSO solvent control wells for each definitive assay was <20%; and 2) the positive control produced a statistically significant induction above 1.5 fold below 64 μM in each definitive assay. The second definitive trial was not valid due to the variability in the DMSO solvent control wells in excess of 20%.
Any other information on results incl. tables
The test article, BTFB, was tested in 3 definitive assays, 2 of which were valid and used; the second definitive assay did not meet the acceptance criteria and was not considered valid due to excessive solvent control variability. Each definitive assay included a set of 4 plates (3 for gene induction, 1 for cytotoxicity assessment). The test article, BTFB, was tested at 12 concentrations ranging from 0.977 to 2000 µM. The positive control, Cinnamic Aldehyde, was tested at 5 concentrations ranging from 4 to 64 µM. A summary of the EC1.5 values (concentration inducing luciferase activity 1.5-fold (i.e., 50% above) that of the solvent controls) and the IC30 and IC50 values (concentrations leading to a 30% and 50% reduction in viability relative to solvent controls, respectively) of the definitive assays are presented in Table 1. Additional luciferase induction information (which was not used for the current prediction model) that includes the Imax (the maximal fold induction) and the CImax (the concentration at which the maximal fold induction occurs), is also presented in Table 1.
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Based on the data from The Induction of Antioxidant-Response-Element Dependent Gene Activity and Cytotoxicity (Using MTT) in the Keratinocyte ARE- Reporter Cell Line KeratinoSens assay, the
test article was predicted to be a skin non-sensitizer.
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