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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 225-591-4 | CAS number: 4948-28-1
- 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:
- weight of evidence
- Study period:
- 2022-02-15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
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:
- 2021-06-14
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- 2012-07-06
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: MatTek Corporation Protocol: In vitro EpiDermTM Skin Irritation Test (EPI-200-SIT) For use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm (EPI-200-SIT)
- Version / remarks:
- 2020-04-12
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: In vitro EpiDermTM Skin Irritation Test (EPI-200-SIT) for use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm (EPI-200)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: MatTek Corporation Protocol: EpiOcularTM Eye Irritation Test (OCL-200-EIT) For the prediction of acute ocular irritation of chemicals: Identification of chemicals not requiring classification and labeling for eye irritation or serious eye damage
- Version / remarks:
- 2021-02-02
- Deviations:
- no
- Remarks:
- The Pre-Test (Assessment of Colored or Staining Materials and Assessment of Direct Test Article Reduction by MTT) was performed according to the MatTek Protocol “EpiOcularTM Eye Irritation Test.
- Principles of method if other than guideline:
- The Pre-Test (Assessment of Colored or Staining Materials and Assessment of Direct Test Article Reduction by MTT) was performed according to the MatTek Protocol “EpiOcularTM Eye Irritation Test.
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- (1α,2α,5α)-2,2,6-trimethylbicyclo[3.1.1]heptan-2-ol
- EC Number:
- 225-591-4
- EC Name:
- (1α,2α,5α)-2,2,6-trimethylbicyclo[3.1.1]heptan-2-ol
- Cas Number:
- 4948-28-1
- Molecular formula:
- C10H18O
- IUPAC Name:
- (1R,2S,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- In an international prevalidation study performed by ECVAM, the in vitro skin irritation test using the human skin model EpiDerm™ and EpiSkin™ and measurement of cell viability by dehydrogenase conversion of MTT into a blue formazan salt have turned out as a sufficiently promising predictor for skin irritancy potential.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Epi-200-SIT Reconstructed Human EpiDerm model purchased from MatTek Corporation (82105 Bratislava, Slovakia)
- Tissue batch number: 36101
- Date of certificate of analysis: 2021-10-27
- Date of initiation of testing: 2021-10-12
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1.5°C
- Temperature of post-treatment incubation: 24 ± 2 hours at room temperature and further 18 ± 2 hours at 37 ± 1.5°C.
REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps: The tissues were gently rinsed with PBS several times
- Observable damage in the tissue due to washing: No
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours ± 5 minutes
- Spectrophotometer: Versamax® (Molecular Devices)
- Wavelength: OD 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: Tissue viability was checked for the tissue batch by the supplier and was found to be within the acceptable range. Concurrent negative controls (NC) were used in each run to demonstrate that viability (with the NC) of the tissues were within a defined historical acceptance range (see attached background material).
- Barrier function: Barrier function was checked for the tissue batch by the supplier and was found to be within the acceptable range. Concurrent positive controls (PC) were used in each run to demonstrate that barrier function and resulting tissue sensitivity of the tissues were within a defined historical acceptance range (see attached background material).
- Contamination: Every tissue batch was checked for biological contaminants. No HIV-1 virus, Hepatitis B or C virus and no bacteria, yeast and other funi were detected.
- Reproducibility: All acceptance criteria were met (for the tissue batch and the tissue replicates used in the study), thus, reproducibility was proven.
NUMBER OF REPLICATE TISSUES: 3 tissue replicates per test item/positive and negative control treatment
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
Since the OD of the test item in deionised water or isopropanol at 570 nm after blank correction was > 0.08 in the first pre-experiment, it was presumed to have the potential to stain the tissue.
- Fresh tissues were used to control for color interference
- N. of replicates: Two controls in duplicates run (2 deionised water treated tissues and 2 test item treated tissues)
- Method of calculation used: Data Correction Procedure I was performed (see "Any other information on materials and methods incl. tables")
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritating or corrosive to skin if the viability after 1 hour exposure and 42 hours post-incubation is equal or less than 50%.
- The test substance is considered to be non-irritating to skin if the viability after 1 hour exposure and 42 hours post-incubation is greater than 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- yes, concurrent MTT non-specific colour control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 25 ± 2 mg (39.7 mg/cm2 according to guideline) - Duration of treatment / exposure:
- 60 minutes (35 minutes at 37 ± 1.5°C and 5 ± 0.5% CO2 and 25 min at room temperature)
- Duration of post-treatment incubation (if applicable):
- 42 ± 4 hours
- Number of replicates:
- The test item and the controls, respectively, were tested in triplicate tissues
Results and discussion
In vitro
Results
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- Mean of 3 tissue replicates
- Run / experiment:
- 1
- Value:
- 6.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: No
- Direct-MTT reduction: No
- Colour interference with MTT: Yes
DEMONSTRATION OF TECHNICAL PROFICIENCY: Prior to routine use of EpiDermTM SIT for regulatory purposes, technical proficiency was demonstrated by correctly predicting the proficiency chemicals listed in OECD TG 439.
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
- Range of historical values: See "Attached background material"
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Remarks:
- Further testing is required to resolve between UN GHS Categories 1 and 2 and decide on the final classification of the test item.
- Conclusions:
- In an in vitro skin irritation study according to OECD guideline 439, the test item was identified as requiring classification and labelling according to UN GHS/ EU CLP “Category 2” or “Category 1”, since the tissue viability after exposure and post-incubation was less or equal to 50%.
- Executive summary:
This in vitro study according to OECD guideline 439 and GLP was performed to assess the skin irritation potential of the test item by means of the Human Skin Model Test. The test item did not prove to be a MTT reducer in the MTT interference pre-experiment. Therefore, additional tests with freeze-killed tissues did not have to be performed. The test item proved to dye water in the color interference pre-experiment since the OD of the test item in deionised water at 570 nm after blank correction was > 0.08. Therefore, additional tests with viable tissues had to be performed. The viability values resulted in these additional tests were used to correct the values gained in the main experiment. Three tissues each of the human skin model EpiDerm™ were treated with the test item, the negative control (DPBS) or the positive control (5% SDS) for 60 minutes. After treatment with the negative control the absorbance values were well within the required range of the acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval, thus assuring the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the viability as compared to the negative control for the 60 minutes treatment interval, thus assuring the validity of the test system. After treatment with the test item, the mean relative viability value was 6.90% compared to the relative absorbance value of the negative control. This value is below the threshold for irritancy of ≤ 50%. Therefore, the test item is considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item is irritant to skin. The test item is identified as requiring classification and labelling according to UN GHS/ EU CLP “Category 2” or “Category 1”, since the tissue viability after exposure and post-incubation is less or equal to 50%. Further testing is required to resolve between UN GHS Categories 1 and 2 and decide on the final classification of the test item.
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.