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EC number: 220-136-6 | CAS number: 2639-63-6
- 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
Endpoint summary
Administrative data
Description of key information
Study conducted to recognised testing guidelines with GLP certification.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16th April 2018 - 20th April 2018
- 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:
- adopted 29 July 2016
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Part B: Methods for the Determination of Toxicity and other health effects, Guideline B.40 BIS: "In Vitro Skin Corrosion: Human Skin Model Test"
- Version / remarks:
- Official Journal of the European Union No. L142, 31 May 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- Appearance: Clear colourless liquid
Purity/Composition: 99.26%
Test item storage: At room temperature protected from light - Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: normal, human-derived epidermal keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- Test for the Interference of the Test Item with the MTT Endpoint:
A test item may interfere with the MTT endpoint if it is colored and/or it is able to directly reduce MTT. The cell viability measurement is affected only if the test item is present on the tissues when the MTT viability test is performed.
Test for Color Interference by the Test Item:
Hexyl Butyrate was checked for possible color interference before the study was started. Some non-colored test items may change into colored items in aqueous conditions and thus stain the skin tissues during the 1-hour exposure. To assess the color interference, 50 µL of the test item or 50 µL Milli-Q water as a negative control were added to 0.3 mL Milli-Q water. The mixture was incubated for approximately 1 hour at 37.0 ± 1.0°C in the dark. At the end of the exposure time the mixture was shaken and it was checked if a blue / purple color change was observed.
Test for Reduction of MTT by the Test Item:
Hexyl Butyrate was checked for possible direct MTT reduction before the study was started. To assess the ability of the test item to reduce MTT, 50 µL of the test item or 50 µL Milli-Q water as a negative control were added to 1 mL MTT (Sigma, Zwijndrecht, The Netherlands) solution (1 mg/mL) in phosphate buffered saline. The mixture was incubated for approximately 1 hour at 37.0 ± 1.0ºC. At the end of the exposure time it was checked if a blue / purple color change or a blue / purple precipitate was observed.
Test System Set Up:
Tissues:
On the day of receipt the tissues were kept on agarose and stored in the refrigerator. On the next day, at least one hour before starting the assay the tissues were transferred to 6-well plates with 0.9 mL DMEM.
Figure 1 - see below (attached)
DMEM (Dulbecco’s Modified Eagle’s Medium)
Supplemented DMEM, serum-free supplied by MatTek Corporation.
MTT medium
MTT concentrate (5 mg/mL) diluted (1:5) with MTT diluent (supplemented DMEM). Both supplied by MatTek Corporation.
Environmental conditions
All incubations, with the exception of the test item incubation of 3 minutes at room temperature, were carried out in a controlled environment, in which optimal conditions were a humid atmosphere of 80 - 100% (actual range 70 - 97%), containing 5.0 ± 0.5% CO2 in air in the dark at 37.0 ± 1.0°C (actual range 35.7 – 37.2°C). Temperature and humidity were continuously monitored throughout the experiment. The CO2 percentage was monitored once on each working day. Temporary deviations from the temperature, humidity and CO2 percentage may occur due to opening and closing of the incubator door. Based on laboratory historical data these deviations are considered not to affect the study integrity.
Test Item Preparation:
No correction was made for the purity/composition of the test item.
The liquid test item was applied undiluted (50 µL) directly on top of the tissue.
Application/Treatment of the Test Item:
The skin tissues were kept in the refrigerator the day they were received. The next day, at least 1 hour before the assay was started the tissues were transferred to 6-well plates containing 0.9 mL DMEM per well. The level of the DMEM was just beneath the tissue (see figure 1). The plates were incubated for approximately 2 hours at 37.0 ± 1.0ºC. The medium was replaced with fresh DMEM just before Hexyl Butyrate was applied. The test was performed on a total of 4 tissues per test item together with a negative control and positive control. Two tissues were used for a 3-minute exposure to Hexyl Butyrate and two for a 1-hour exposure. Fifty µL of the undiluted test item was added into the 6-well plates on top of the skin tissues.
For the negative and positive controls, 2 tissues were treated with 50 µL Milli-Q water (negative control) and 2 tissues were treated with 50 µL 8N KOH (positive control) for both the 3-minute and 1-hour time point.
After the exposure period, the tissues were washed with phosphate buffered saline (Invitrogen Corporation, Breda, The Netherlands) to remove residual test item. The skin inserts were carefully dried. Rinsed tissues were kept in 24 well plates on 300 µL DMEM until 6 tissues
(= one application time) were dosed and rinsed.
Cell Viability Measurement:
The DMEM was replaced by 300 µL MTT-medium and tissues were incubated for 3 hours at 37°C in air containing 5% CO2. After incubation the tissues were washed with PBS and formazan was extracted with 2 mL isopropanol (MatTek corporation) over night at room temperature. The amount of extracted formazan was determined spectrophotometrically at 570 nm in triplicate with the TECAN Infinite® M200 Pro Plate Reader. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- The liquid test item was applied undiluted (50 µL) directly on top of the tissue.
- Duration of treatment / exposure:
- 3 minutes for two tissues
1 hour for two other tissues - Duration of post-treatment incubation (if applicable):
- The DMEM was replaced by 300 µL MTT-medium and tissues were incubated for 3 hours at 37°C in air containing 5% CO2.
- Number of replicates:
- 2 replicates for each exposure time
- Irritation / corrosion parameter:
- other: other: tissue viability
- Value:
- 101
- Remarks on result:
- other:
- Remarks:
- Basis: other: percentage of control. Time point: 3 minutes. Remarks: Negative control = 100%; Positive control = 14%. (migrated information)
- Irritation / corrosion parameter:
- other: other: tissue viability
- Value:
- 92
- Remarks on result:
- other:
- Remarks:
- Basis: other: percentage of control. Time point: 1 hour. Remarks: Negative control = 100%; Positive control = 8%. (migrated information)
- Other effects / acceptance of results:
- Hexyl Butyrate was checked for color interference in aqueous conditions and possible direct MTT reduction by adding the test item to MTT medium. Because the solutions did not turn blue / purple nor a blue / purple precipitate was observed it was concluded that the test item did not interfere with the MTT endpoint.
The mean absorption at 570 nm measured after treatment with Hexyl Butyrate and controls are presented in Appendix 1, Table 1. The individual OD570 measurements are presented in Appendix 2.
Table 2 shows the mean tissue viability obtained after 3-minute and 1-hour treatments with Hexyl Butyrate compared to the negative control tissues. Skin corrosion is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after the 3-minute and 1-hour treatments with Hexyl Butyrate compared to the negative control tissues was 101% and 92% respectively. Because the mean relative tissue viability for Hexyl Butyrate was not below 50% after 3 minutes treatment and not below 15% after 1 hour treatment Hexyl Butyrate is considered to be not corrosive.
The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the acceptance limits of OECD 431 (lower acceptance limit ≥0.8 and upper acceptance limit ≤2.8) and the laboratory historical control data range (See Appendix 3). The mean relative tissue viability following the 1-hour exposure to the positive control was 6.8%.
In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was ≤ 17%, indicating that the test system functioned properly (Appendix 1, Table 3). - Interpretation of results:
- GHS criteria not met
- Conclusions:
- An in vitro skin corrosion test was conducted according to OECD guideline 431 and GLP principles. It is concluded that this test is valid and that the test substance is not corrosive in the in vitro skin corrosion test.
- Executive summary:
The objective of this study was to evaluate Hexyl Butyrate for its ability to induce skin corrosion on a human three dimensional epidermal model (EpiDerm (EPI-200)). The possible corrosive potential of Hexyl Butyrate was tested through topical application for
3 minutes and 1 hour.The study procedures described in this report were based on the most recent OECD and EC guidelines.
Batch 202509 of Hexyl Butyrate was a clear colourless liquid. Hexyl Butyrate was applied undiluted (50 µL) directly on top of the skin tissue.
The positive control had a mean relative tissue viability of 6.8% after the 1-hour exposure. The absolute mean OD570(optical density at 570 nm) of the negative control tissues was within the acceptance limits of OECD 431 (lower acceptance limit ≥0.8 and upper acceptance limit ≤2.8) andthe laboratory historical control data range. In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was ≤17%,indicating that the test system functioned properly.
Skin corrosion is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 3-minute and 1-hour treatments with Hexyl Butyrate compared to the negative control tissues was 101% and 92%, respectively. Because the mean relative tissue viability for Hexyl Butyrate was not below 50% after the 3-minute treatment and not below 15% after the 1-hour treatment Hexyl Butyrate is considered to not be corrosive.
In conclusion, Hexyl Butyrate is not corrosive in the in vitro skin corrosion test under the experimental conditions described in this report.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Justification for classification or non-classification
Hexyl butyrate was shown to be classified as neither irritating nor corrosive to human skin according to EC 1278/2008.
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