Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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:
- 31 March 2020 to 3 April 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 guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: EPA TSCA (40 CFR 792)
- Deviations:
- yes
- Remarks:
- See "Any other information on materials and methods incl. tables"
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 luciferase KeratinoSens™ test method)
- Version / remarks:
- 25 June 2018
- Deviations:
- yes
- Remarks:
- See "Any other information on materials and methods incl. tables"
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Study was conducted in compliance with EPA TSCA (40 CFR 792). Study designed based off of OECD Guideline 442D.
- Type of study:
- ARE-Nrf2 luciferase KeratinoSens™ test method
- 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:
- Reaction mass of 2(R/S)‐1‐{[(1R,2S,5R,8S)‐4,4,8‐trimethyltricyclo[6.3.1.0~2,5~]dodecan‐1‐yl]oxy}pentan‐2‐o and 2(R/S)‐1‐{[(1S,2S,5R,8R)‐1,4,4‐trimethyltricyclo[6.3.1.0~2,5~]dodecan‐8‐yl]oxy}pentan‐2‐ol
- Molecular formula:
- C20H36O2
- IUPAC Name:
- Reaction mass of 2(R/S)‐1‐{[(1R,2S,5R,8S)‐4,4,8‐trimethyltricyclo[6.3.1.0~2,5~]dodecan‐1‐yl]oxy}pentan‐2‐o and 2(R/S)‐1‐{[(1S,2S,5R,8R)‐1,4,4‐trimethyltricyclo[6.3.1.0~2,5~]dodecan‐8‐yl]oxy}pentan‐2‐ol
- Test material form:
- liquid: viscous
- Details on test material:
- Chemical name: 1‐[(4,4,8‐trimethyltricyclo[6.3.1.02,5]dodecan‐1‐yl)oxy]pentan‐2‐ol and 1‐[(1,4,4‐trimethyltricyclo[6.3.1.02,5]dodecan‐8‐yl)oxy]pentan‐2‐ol and isomers
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 high throughput 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 signaling pathway with the repressor protein Keap1 and the transcription fact or 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 considered valid and used to determine the maximal induction (Imax), the concentration for maximal gene induction (CImax), the EC1.5 value (concentration for a statistically significant induction of 50% above solvent controls), and a mean IC50 AND IC30 (concentrations leading to 50% and 30% viability, respectively, as compared to solvent controls) for the test substance. 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 Induction of Antioxidant Response Element-Dependent Gene Activity and Cytotoxicity (Using MTT) in the Keratinocyte ARE-Reporter Cell Line KeratinoSens™ Assay was performed to determine the skin sensitization potential of the test article, FRET 18-0091, supplied by International Flavours & Fragrances Inc.. The laboratory phase of this study was conducted from 31 March 2020 to 3 April 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.- Vehicle / solvent control:
- DMSO
- Positive control:
- cinnamic aldehyde [442D]
Results and discussion
- Positive control results:
- The positive control, cinnamic aldehyde, had a mean EC 1.5 of 5.81 μM and mean IC50 of >64 μM.
In vitro / in chemico
Resultsopen allclose all
- Key result
- Group:
- test chemical
- Run / experiment:
- mean
- Parameter:
- IC30 [442D]
- Value:
- 14.93 µM
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Group:
- test chemical
- Run / experiment:
- mean
- Parameter:
- EC 1.5 [442D]
- Value:
- 3.71 µM
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Group:
- test chemical
- Run / experiment:
- mean
- Parameter:
- IC50 [442D]
- Value:
- 13.23 µM
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- 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 first definitive trial was not valid due to excess variability in the DMSO solvent control wells.
Any other information on results incl. tables
The test article, FRET 18-0091, was tested in 3 definitive assays. The first definitive assay was not considered valid due to excessive variability in the solvent control wells. Each definitive assay included a set of 4 plates (3 for gene induction, 1 for cytotoxicity assessment). The test article, FRET 18-0091, 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. A summary graph representing the luciferase fold induction and the cell viability for each tested concentration of the test article is included following Table 1.
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Based upon 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, FRET 18-0091, was predicted to be a skin sensitizer.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.