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EC number: 225-207-5 | CAS number: 4717-96-8
- 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:
- 2016-12-07 to 2017-02-10
- 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:
- 2015
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- Tetrahydro-4-methyl-2H-pyran
- EC Number:
- 225-207-5
- EC Name:
- Tetrahydro-4-methyl-2H-pyran
- Cas Number:
- 4717-96-8
- Molecular formula:
- C6H12O
- IUPAC Name:
- 4-methyltetrahydro-2H-pyran
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Chemical name: 4-methyltetrahydropyran (MTHP)
- CAS no.: 4717-96-8
- EC-no.: not assigned
- Source and lot/batch No.of test material: Kuraray / MTHP-72715
- Expiration date of the lot/batch: not stated
- Molecular weight: 100.16 g/mol
- Purity: >99%
Test animals / tissue source
- Species:
- other: EpiOcular (reconstructed human cornea-like epithelium)
- Strain:
- other: supplied by MatTex Corporation
- Details on test animals or tissues and environmental conditions:
- TEST KIT
- Source: MatTex Corporation
- Type: Reconstructed human cornea-like epithelium
- Lot no.: 20973
Cell culture media:
- Assay medium (MatTex Corporation)
- Lot no.: 120516MWKC
- Vehicle / postive controls: deionised water / Methyl acetate (MatTex Corporation)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 37°C, humidified incubator
- CO2 (%): 5%
IN-LIFE DATES: 12 December 2016 to 13 December 2016
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 uL
- Concentration (if solution): dosed as recieved (neat)
VEHICLE
- Amount(s) applied (volume or weight with unit): 50 uL
- Concentration (if solution): n/a
- Lot/batch no. (if required): municipal water purified using a water purifier to yield deionised water. Deionised water filter sterilised using a 0.22 um filter.
- Purity: sterile - Duration of treatment / exposure:
- 30 minutes / application to tissue surface
- Duration of post- treatment incubation (in vitro):
- 2 h
- Number of animals or in vitro replicates:
- 2 replicates/treatment group
- Details on study design:
- Pre-experimental checks:
To check the non-specific MTT-reducing capability of the test article 50 µL of the test article was mixed with 1 mL MTT (1 mg MTT/mL) medium and incubated for 3 hours and observed visually after stirring. For comparison, only 1 mg/mL MTT solution was treated in a similar manner
Procedure:
- Pre-incubation:
One 6-well plate was prepared for each treatment, 2 culture inserts and the medium (1.0 mL) was added to each well of the plate and pre-incubated for 60 minutes in a CO2 incubator. After 60 minutes of pre-incubation the plates were taken out of the CO2 incubator and culture inserts were transferred to the lower wells of the 6-well plates. The plates were incubated for 18-19 h in CO2 incubator.
- Exposure to the test material and rinsing:
After pre-incubation tissues were treated with each dose group in duplicate, starting with the negative control. The test article (50 µL) was added to the surface of the tissues. When the test materials were not spread over the entire tissue surface, the culture inserts were gently tapped to penetrate the test material into the entire tissue. The exposure time was 30 minutes in a CO2 incubator.
At the end of the exposure period tissues were washed with PBS to remove any residual test article. Excess PBS was removed by blotting bottom with blotting paper. After completion of rinsing, the culture inserts were promptly transferred to a 12 well plate containing medium and left to stand for 12 minutes. At the end of the 12 minute period, the inserts were transferred to a 6-well plate containing medium and incubated for 2 h in a CO2 incubator.
Cytotoxicity analysis (MTT):
Following the post-incubation period, the inserts were transferred in a prepared 24-well plate containing 300 µL pre-warmed MTT medium (1 mg/mL) and further incubated for 3 h, under the same conditions as previously stated.
After the 3 h MTT incubation period, the inserts were transferred to a 24-well plate containing isopropanol (2 mL/well) in order to extract the formazan. Extraction was carried out protected from light at room temperature for 2 hours.
The extract were transferred into a 96-well plate and the optical density was measured at 570 nm without reference wavelength in a plate spectrophotometer.
Results and discussion
In vitro
Results
- Irritation parameter:
- in vitro irritation score
- Value:
- ca. 4.3
- 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:
- refer to "Any other information on results incl. tables"
Any other information on results incl. tables
Formulation analysis:
None conducted.
Pre-experiment:
The mixture of test article and MTT medium showed no reduction of MTT compared to the solvent. The mixture did not turn blue/purple.
The mixture of the test article and aqua destain showed no colouring detectable by unaided eye-assessment.
Eye Irritation:
The test article showed irritant effects. The mean relative tissue viability was <60% (4.3%) after 30 minute treatment (+2 hour post-incubation). The positive control viability was <50%, therefore confirming that irritants were detected with the test system.
The controls confirmed the validity of the study. The mean OD550of the vehicle control values was 1.279. The mean relative tissue viability of the positive control was <50% (38%). The difference in viability of each dose group was <20%.
Table
CA 7.3.2/01-1:
Summary of in vitro EpiOcular result following application of MTHP
Parameter |
Negative control |
MTHP |
Positive control |
Mean OD 570 (difference) |
1.279 (0.097) |
0.055 (0.004) |
0.481 (0.112) |
Mean relative tissue viability (%) (difference) |
100 (7.6) |
4.3 (0.4) |
37.6 (8.8) |
Deficiencies:
None.
Conclusion
Under the conditions of this study MTHP showed irritant effects. The mean relative tissue viability was <60% (4.3%) after a 30 minute exposure (+ 2 hour post-incubation). Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP requires classification and labelling. However, this test guideline cannot resolve between GHS Categories 1 and 2, typically therefore further classification on eye irritation/corrosion is required to decide on the final classification. However, MTHP is confirmed to cause skin corrosivity, therefore no further testing is required for ocular irritation/corrosion, with MTHP considered corrosive to the eye.
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Remarks:
- MTHP is corrosive to skin, therefore no further testing is required for ocular irritation/corrosion, with MTHP considered corrosive to the eye
- Conclusions:
- Under the conditions of this study MTHP showed irritant effects. The mean relative tissue viability was <60% (4.3%) after a 30 minute exposure (+ 2 hour post-incubation). Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP requires classification and labelling. However, this test guideline cannot resolve between GHS Categories 1 and 2, typically therefore further classification on eye irritation/corrosion is required to decide on the final classification. However, MTHP is confirmed to cause skin corrosivity, therefore no further testing is required for ocular irritation/corrosion, with MTHP considered corrosive to the eye.
- Executive summary:
The potential of the test article to induce ocular irritation was analysed using the three-dimensional human eye EpiOcular model comprising a reconstructed human cornea-like epithelium.
In the present study MTHP (Tetrahydro-4 -methyl-2H-pyran) was applied topically to the EpiOcular tissue for 30 minutes followed by a 2 hour post-incubation period and immediate determination of cytotoxic effects via the MTT reduction assay.
Irritant potential of the test article was predicted from the relative mean tissue viabilities obtained compared to the corresponding negative control tissues concurrently treated with distilled water. The positive control, methyl acetate viability was <50%, thereby confirming that irritants could be detected in this test system.
The test item showed irritant effects. The mean relative tissue viability (% vehicle control) was <60% (21%) after 30 minute treatment and 2 hour post incubation.
Under the conditions of this study MTHP showed irritant effects. The mean relative tissue viability was <60% (4.3%) after a 30 minute exposure (+ 2 hour post-incubation). Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP requires classification and labelling. However, this test guideline cannot resolve between GHS Categories 1 and 2, typically therefore further classification on eye irritation/corrosion is required to decide on the final classification. However, MTHP is confirmed to cause skin corrosivity, therefore no further testing is required for ocular irritation/corrosion, with MTHP considered corrosive to the eye.
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