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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 26 June 2017 - 30 June 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
- Version / remarks:
- 28 July 2015
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Physical appearance: white powder with lumps
- Test item storage: at room temperature protected from light
Constituent 1
- Specific details on test material used for the study:
- - pH (1% in water, indicative range): 5.12 - 4.78
Test animals / tissue source
- Species:
- human
- Details on test animals or tissues and environmental conditions:
- TEST SYSTEM:
The EpiOcular tissue construct is a nonkeratinized epithelium prepared from normal human keratinocytes. It models the cornea epithelium with progressively stratified, but not cornified cells. A cell suspension is seeded into the insert in specialized medium. After an initial period of submerged culture, the medium is removed from the top of the tissue so that the epithelial surface is in direct contact with the air. This allows the test material to be directly applied to the epithelial surface in a fashion similar to how the corneal epithelium would be exposed in vivo.
- Justification: In the interest of sound science and animal welfare, a sequential testing strategy is recommended to minimize the need of in vivo testing. One of the validated in vitro eye irritation tests is the EpiOcular test, which is recommended in international guidelines and scientific publications (e.g. OECD).
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Duration of treatment / exposure:
- 6 hours ± 15 minutes
- Duration of post- treatment incubation (in vitro):
- 18 hours (after a post-soak period of 25 ± 2 minutes)
- Number of animals or in vitro replicates:
- Test item: 2 tissues
Negative control (MilliQ water): 2 tissues
Positive control (Triton X (0.3%)): 2 tissues - Details on study design:
- TEST SYSTEM
- RhCE tissue construct used, including batch number: EpiOcular™ (OCL-200-EIT MatTek Corporation, Lot: 23487)
The EpiOcular tissue construct is a non-keratinized epithelium (0.6 cm2) prepared from normal human keratinocytes.
- Doses of test chemical and control substances used: 54.8 to 58.6 mg of test substance, 50 μL of the positive control and 50 μL of the negative control.
- Before the assay was started all the tissues were pre-wetted with 20 μL of Ca2+Mg2+-Free-DPBS and incubated at standard culture conditions for 30 ± 2 minutes.
- Exposure: 6 hours ± 15 minutes at 37.0 ± 1.0°C
- Removal test item: rinsing with Ca2+Mg2+-free D-PBS (brought to room temperature)
- Post-exposure immersion: After rinsing the cell culture inserts were each dried carefully and immediately transferred to and immersed in 5 ml of previously warmed Assay Medium (room temperature) in a pre-labeled 12-well plate for a 25 ± 2 minute immersion incubation at room temperature (Post-Soak).
- Post-exposure incubation: After the Post-Soak period cell culture inserts were each dried carefully and transferred to the 6-well plate containing 1.0 ml of warm Assay Medium and were incubated for 18 hours ± 15 minutes at 37°C.
- Justification for the use of a different positive control than neat methyl acetate: The positive control (Methyl Acetate) was not supplied with the kit. Therefore Triton X (0.3%) was used as a positive control.Triton X 0.3% shows a response which could be expected based on the ET-50 (exposure time required to reduce tissue viability by 50%) of this kit which was 29.81 minutes, therefore this does not affect the study outcome.
Interference of the test item with the MTT endpoint
- Test item was checked for possible colour intereference before the study started by adding 50 mg of the test item to 1.0 mL Milli-Q water and incubated for 1 hour. At the end of the exposure time, the absorbance of the solutions was determined spectrophotometrically at 570 nm in duplicate with the TECAN Infinite® M200 Pro Plate Reader.
- For MTT reduction 50 mg of the test item was added to 1mL MTT solution. This mixture was incubated for 3 hours. After incubation, the mixture was checked for a blue/purple colour.
- All incubations, with the exception the exposure and post-exposure immersion at room temperature, were carried out in a controlled environment:
- Humidity: 77-91%
- CO2: 5.0 ± 0.5%
- Temperature: 36.9 - 37.5°C.
CELL VIABILITY MEASUREMENT
After incubation, cell culture inserts were dried carefully to remove excess medium. The cell culture inserts were transferred into a 24-wells plate prefilled with 0.3 ml MTT-medium (1.0 mg/ml). The tissues were incubated for 180 ± 10 minutes at 37°C. After incubation with MTT-medium the tissues were placed on blotting paper to dry the tissues. Formazan was extracted with 2 ml isopropanol for 2 - 3 hours at room temperature with gentle shaking. The amount of extracted formazan was determined spectrophotometrically at 570 nm in duplicate with the TECAN Infinite® M200 Pro Plate Reader. The amount of extracted formazan was determined spectrophotometrically at 570 nm in duplicate with the TECAN Infinite® M200 Pro Plate Reader.
Cell viability was calculated for each tissue as a percentage of the mean of the negative control tissues. Eye hazard potential of the test item was classified according to remaining cell viability following exposure of the test item.
Data evaluation:
* The test chemical is identified as not requiring classification and labelling according to UN GHS (No Category) if the mean percent tissue viability after exposure and post-exposure incubation is more than (>) 60%. In this case no further testing in other test methods is required.
* The test chemical is identified as potentially requiring classification and labelling according to UN GHS (Category 2 or Category 1) if the mean percent tissue viability after exposure and postexposure incubation is less than or equal (≤) to 60%.-
Acceptability of the assay
The in vitro eye irritation test is considered acceptable if it meets the following criteria:
a) The absolute mean OD570 of the two tissues of the negative control should reasonably be > 0.8 and < 2.5.
b) The mean relative tissue viability of the positive control should be <50% relative to the negative control.
c) The SD calculated from individual % tissue viabilities of the two identically treated replicates should be <20%.
Results and discussion
In vitro
Results
- Irritation parameter:
- other: Mean tissue viability (% of negative control)
- Run / experiment:
- Single run
- Value:
- 101
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- Mean tissue viability: 100%
- Positive controls validity:
- valid
- Remarks:
- Mean tissue viability: 1.87%
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Colour interference of the test item: no
- Reduction of MTT by the test item: no
- Visible damage on test system: no
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes, the OD570 measurements of the negative control tissues were between 0.8 and 2.5 (i.e., a mean of 1.574 ± 0.025), which was in the historical control data range.
- Acceptance criteria met for positive control: Yes, the positive control tissues had a mean tissue viability <50% (i.e., 1.87%).
- The standard deviation from individual % tissue viabilities of the two identically treated replicates was <20% (i.e., <2%).
Any other information on results incl. tables
Table 1 Historical control data for EpiOcular™ Studies
|
Negative control (absorption; OD570) |
Positive control (absorption; OD570) |
Positive control (viability; %) |
Range |
1.228 – 2.090 |
0.320 – 0.535 |
17.80 – 34.18 |
Mean |
1.53 |
0.42 |
27.55 |
SD |
0.23 |
0.07 |
5.31 |
n |
12 |
12 |
12 |
SD = Standard deviation
n = Number of observations
The above mentioned historical control data range of the controls were obtained by collecting all data over the period of January 2013 to May 2017.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Not classified according to Regulation (EC) No. 1272/2008
- Conclusions:
- Based on the evaluation of the eye hazard potential with ROC-118 using the EpiOcular cornea epithelial model and performed according to OECD guideline and GLP principles, it is concluded that ROC-118 is not irritant for the eye. The substance is not classified according to GHS and according to Regulation (EC) No. 1272/2008.
- Executive summary:
An in vitro eye irritation study was performed according to OECD guideline and GLP principles to test the eye hazard potential of ROC-118. The substance was directly applied on top of the Reconstructed Human EpiOcular model for 6 hours ± 15 minutes at an amount of 54.8 -58.6 mg. After the exposure period, the tissues were rinsed and incubated for an additional 18 hours prior to determination of the cytotoxic effect. The relative mean tissue viability after 6 hours ± 15 minutes treatment with the test substance, compared to the negative control, was 101%. The acceptability criteria for the positive and negative control were met. Based on these results, ROC-118 is considered to be non-irritant to the eyes and is not classified according to GHS and according to Regulation (EC) No. 1272/2008.
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.
Čeprav agencija ECHA veliko spletnega gradiva objavlja v vašem jeziku, je ta stran deloma še vedno v angleščini. Več informacij o večjezikovni praksi agencije.
Dobrodošli na spletišču agencije ECHA Vsebina na tej strani ni v celoti podprta z brskalnikom Internet Explorer 7 (in starejšimi različicami). Prosimo, nadgradite vaš brskalnik Internet Explorer na novejšo različico.
Ta stran uporablja piškotke za zagotavljanje najboljše možne uporabniške izkušnje na našem spletišču.
Preberite več o tem, kako uporabljamo piškotke.