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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
Acute Toxicity: dermal
Administrative data
- Endpoint:
- acute toxicity: dermal
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because the substance is classified as corrosive to the skin
Cross-reference
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017-04-14 to 2017-05-18
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
- Version / remarks:
- 2016
- Deviations:
- no
- GLP compliance:
- yes
- 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 system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- skin obtained from plastic surgery from a single donor
- Source strain:
- other: Normal human epidermal keratinocytes (NHEK), derived from neonatal-foreskin tissue
- Details on animal used as source of test system:
- TEST KIT
- Source: MatTex Corporation
- Type: Normal human epidermal keratinocytes (NHEK), derived from neonatal-foreskin tissue
- Lot no.: 25765
Cell culture media:
- Assay medium (MatTex Corporation)
- Lot no.: 041217CMHA
- Vehicle / postive controls: deionised water / 8N KOH (Wako Pure Chemical)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 37°C, humidified incubator
- CO2 (%): 5%
IN-LIFE DATES: 18 April 2017 to 19 April 2017 - Vehicle:
- unchanged (no vehicle)
- Details on test system:
- 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 1 hour and observed visually after stirring.
Nylon mesh compatibility was also assessed, using the same methodology as outlined above. The nylon mesh was evaluated microscopically.
Procedure:
- Pre-incubation:
One 6-well plate was prepared for each 3 culture insert and the medium (0.9 mL) was added to each well of the plate and pre-incubated for 60 minutes in a CO2 incubator.
- Skin corrosion test:
3 and 60 minute exposures were conducted. 50 uL of the test article, vehicle (distilled water) and positive (8N KOH) controls were applied onto each tissue surface at 45 second intervals. Duplicate tissues were used for each dose level. After the exposure, a nylon mesh was placed on each tissue surface to spread the substances over the tissue surface. The 45 second interval allowed sufficient time for both application and washing procedures at the end of the exposure.
After the initial dosing of the 60 minute application, the plate was placed into the incubator for the remainder of the exposure period was reached.
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. The inserts were placed into a new 24 well plate filled with 300 uL/well of fresh medium.
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 tissues, MTT medium was removed and 2 mL of 2-propanol was added to the tissue inserts to allow formazan extraction from the tissues. Plates were placed into a plastic bag and extraction was performed at room temperature for 2 h or more using a plate shaker.
The 200 uL of 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. 2-propanol was used as a blank.
Cell viability was calculated as follows:
Cell viability (%) = (OD of each tissue / Mean OD of the negative control group) x 100
Tissue binding test was carried using the same procedure as described above, with the exception of medium without MTT was used. After the measuring of OD, the staining ratio was calculated by the following formula:
Staining ratio (%) = (OD of each tissue [without MTT] / Mean OD of the negative control group [without MTT]) x 100 - Control samples:
- yes, concurrent vehicle
- Amount/concentration applied:
- 50 uL of test article
- Duration of treatment / exposure:
- single exposure / 3 and 60 minutes
- Duration of post-treatment incubation (if applicable):
- 42 h
- Number of replicates:
- 2 replicates/dose
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 minute exposure
- Value:
- ca. 97.4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- no indication of corrosivity
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 minute exposure
- Value:
- ca. 4.2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- positive indication of corrosivity
- Other effects / acceptance of results:
- refer to "Any other information on results incl. tables"
- Interpretation of results:
- Category 1A (corrosive) based on GHS criteria
- Conclusions:
- Under the conditions of this study the MTHP showed corrosion effects. The mean relative tissue viability was>50% (97.4%) after the 3 minute exposure, but <15% (8.4%) after the 60 minute treatment (+42 hour post-incubation). Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP is classified as Skin corrosion, Category 1A.
- Executive summary:
The potential of the test article to induce skin corrosion was analysed using the three-dimensional human skin model EPIDERMTM comprising a reconstructed epidermis with a functional stratum corneum.
In the present study MTHP was applied topically to the EPIDERMTM tissue for 3 and 60 minutes followed by a 42 hour post-incubation period and immediate determination of cytotoxic effects via the MTT reduction assay.
Corrosivity 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, 8N potassium hydroxide viability was <20% following a 60 minute exposure, thereby confirming that corrosivity could be detected in this test system.
The test article showed corrosivity effects during the prolonged exposure (60 minutes). The mean relative tissue viability was >50% (97.4%) after the 3 minute exposure, but <15% (8.4%) after the 60 minute treatment (+ 42 hour post-incubation). In accordance with STEP 2 of the judgement criteria, as tissue viability was <25% following the 3 minute exposure, MTHP is deemed to be corrosive to skin, Category 1A.
Under the conditions of this study the MTHP showed corrosion effects. The mean relative tissue viability was>50% (97.4%) after the 3 minute exposure, but <15% (8.4%) after the 60 minute treatment (+42 hour post-incubation). Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP is classified as Skin corrosion, Category 1A.
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
Skin corrosion:
The test article showed corrosivity effects during the prolonged exposure (60 minutes) following STEP 1 analysis. The mean relative tissue viability was >50% (97.4%) after the 3 minute exposure, but <15% (8.4%) after the 60 minute treatment (+ 42 hour post-incubation). In accordance with STEP 2 of the judgement criteria, as tissue viability was <25% following the 3 minute exposure, MTHP is deemed to be corrosive to skin, Category 1A.
The positive control viability was <15% (1.6%) after the 60 minute treatment, following a 42 hour post-incubation therefore confirming that corrosivity was detected with the test system.
The controls confirmed the validity of the study. The mean OD550for the 3 minute and 60 minute negative control groups were 1.725 and 1.799, respectively.
Table CA 7.3.1/02-1: Summary of in vitro EPIDERM corrosivity result following application of MTHP
Parameter |
Negative control |
MTHP |
Positive control |
3 minute exposure |
|||
OD 570 nm |
1.725 |
1.681 |
0.148 |
Mean relative tissue viability (%) ±CV |
100 ±6.5 |
97.4 ±0.3 |
8.6 ±12.3 |
60 minute exposure |
|||
OD 570 nm |
1.799 |
0.075 |
0.028 |
Mean relative tissue viability (%) ±CV |
100 ±1.3 |
4.2 ±8.4 |
1.6 ±0.0 |
Deficiencies:
None.
Conclusion
Under the conditions of this study the MTHP showed corrosion effects. The mean relative tissue viability was>50% (97.4%) after the 3 minute exposure, but <15% (8.4%) after the 60 minute treatment (+42 hour post-incubation). Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP is classified as Skin corrosion, Category 1A.
Data source
Materials and methods
Results and discussion
Applicant's summary and conclusion
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