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EC number: 236-109-7 | CAS number: 13170-05-3
- 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:
- key study
- Study period:
- 2018-04-25 - 2018-05-25
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
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:
- OECD Guideline for the Testing of Chemicals No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method, 28 July 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- Commission Regulation (EC) No. 640/2012, L 193, Part B.46. “In vitro Skin Irritation: Reconstructed Human Epidermis Test Method” 06-Jul-2012
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Bis[4-(tert-butyl)benzoato-O]hydroxyaluminium
- EC Number:
- 236-109-7
- EC Name:
- Bis[4-(tert-butyl)benzoato-O]hydroxyaluminium
- Cas Number:
- 13170-05-3
- Molecular formula:
- C22H27AlO5
- IUPAC Name:
- aluminum hydroxide bis(4-tert-butylbenzoate)
- Test material form:
- solid: particulate/powder
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other:
- Source strain:
- other: n/a, human
- Details on animal used as source of test system:
- n/a
- Justification for test system used:
- In the interest of sound science and animal welfare, a sequential testing strategy is recommended to minimise the need of in vivo testing. One of the validated in vitro skin irritation tests is the EPISKIN test, which is recommended in international guidelines (e.g. OECD and EC).
This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
This test method is able to detect chemicals that cause skin irritation, i.e. produce reversible damage to the skin and allows for hazard identification in accordance with UN GHS “Category 2”. Depending on the regulatory framework it can also be used to identify non-classified chemicals. - Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: reconstituted three-dimensional human skin model EpiDermTM (MatTek). The EpiDermTM tissues were provided as kits (e.g. EPI-200-SIT, MatTek), consisting of the following components relevant for this study:
1x sealed 24-well plate containing e.g. 24 reconstructed epidermis units (area: 0.63 cm2); each reconstructed epidermis is attached to a cell culture insert and maintained on nutritive agar for transport (Lot No.: 25899 for main experiment, 25883 (killed tissues) and 28615 (viable tissues) for additional controls)
2x 24-well plates
8x 6-well plates
1x bottle of assay medium (DMEM-based medium, Lot No.: 041918TMB, 051718TMP)
1x bottle of DPBS Rinse Solution (Lot No.: 010418ISA, 051518ISA)
1x 1 vial 5% SDS Solution (TC-SDS-5%)
25 pieces Nylon Mesh circles (8 mm diameter, 200 µm pore)
- Tissue batch number(s): Lot No.: 25899 for main experiment, 25883 (killed tissues) and 28615 (viable tissues) for additional controls
- Production date: Lot No.: 25899: 2018-04-25 , 25883: 2018-02-28 and 28615: 2018-05-23
- Date of initiation of testing: 2018-04-25
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: After dosing of all tissues, all tissue plates were transferred to a humidified incubator at 37 ± 1 °C, 5.0% CO2, for 35 ± 1 min. Afterwards all plates were removed from the incubator and placed under the sterile flow for the remaining time until the 60 ± 1 min incubation time of the first dosed tissue was over.
- Temperature of post-treatment incubation (if applicable): The tissue plates were post-incubated at 37 ± 1 °C, 5.0% CO2, humidified to 95%, for 24 ± 2 h. Following this incubation the tissues were transferred to new wells containing 0.9 mL fresh assay medium and incubated for additional 18 ± 2 h at 37 ± 1 °C.
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: The tissues were washed by filling and emptying the inserts 15 times with DPBS using a constant stream in about 1.5 cm distance from the tissue surface, this process also occurred sequentially, e.g. in one-minute intervals. Subsequently, the inserts were completely submerged three times in 150 mL DPBS and shaken to remove rests of the test item. Finally, the inserts were rinsed once from the inside and the outside with sterile DPBS. Excess DPBS was removed by blotting the bottom with blotting paper. The inserts were placed in prepared new 6-well plates containing 0.9 mL pre-warmed fresh assay medium per well and the tissue surface was dried using a sterile cotton tip.
- Observable damage in the tissue due to washing: none stated
- Modifications to validated SOP: non stated
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration:
MTT stock solution: 5 mg/mL MTT (Sigma, Lot MKBZ5197V, VWR; Lot 0977C002) in PBS (Gibco; Lot No.: 1909266, 1943443, 1943446)
MTT medium: MTT stock solution was diluted 1 + 4 with DMEM-based medium (final concentration 1 mg/mL)
To check the non-specific MTT-reducing capability of the test item 25 mg of the test item were mixed per 1 mL MTT medium.
- Incubation time: 60 min at 37 +/- 1 °C
- Spectrophotometer: plate spectrophometer
- Wavelength: 570 nm
- Filter: filter band pass
- Filter bandwidth: maximum +/- 30 nm
NUMBER OF REPLICATE TISSUES: 3 tissues per dose group.
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- killed tissues
- N. of replicates : 2
- Method of calculation used: MTT (NSMTT) was calculated relative to negative control of living tissues (NK) according to the following formula: NSMTT [%] = [(ODKT - ODKU)/ODNK]*100
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 3
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
Irritant potential of the test item was predicted from the relative mean tissue viabilities compared to the negative control tissues concurrently treated with DPBS.
- The test substance is considered to be irritant to skin if the tissue viability after exposure and post-incubation is less or equal to 50% in accordance with regulation EC 1272/2008 (UN GHS “Category 2”). Further testing is required to resolve between UN GHS categories 1 and 2 and decide on the final classification of the test substance.
- The test substance is considered to be non-irritant to skin if the tissue viability after exposure and post-treatment incubation is more than 50% in accordance with UN GHS “No Category”. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg + 25 µL DPBS
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DPBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL 5% SDS solution - Duration of treatment / exposure:
- 60 ± 5 min
- Duration of post-treatment incubation (if applicable):
- 18 ± 3 h
- Number of replicates:
- The test was performed on a total of 3 tissues per dose group.
Results and discussion
In vitro
Results
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean relative tissue viability
- Value:
- 100.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Visible damage on test system: none stated
- Direct-MTT reduction: Yes
- Colour interference with MTT: The mixture turned blue/purple
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes. The mean absolute OD570 of the three negative control tissues was >/= 0.8 and ≤ 2.8 (1.849).
- Acceptance criteria met for positive control: Yes. The mean relative tissue viability (% negative control) of the positive control was ≤ 20% (3.2%).
- Acceptance criteria met for variability between replicate measurements: Yes. Standard deviation of viability of replicate tissues of all dose groups was ≤ 18% (0.4% - 2.8%).
Applicant's summary and conclusion
- Interpretation of results:
- other: not classified based on EU-GHS criteria
- Conclusions:
- The study was conducted under GLP according to OECD guideline 439 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations, the validity criteria are fulfilled, positive and negative controls gave the appropriate response. Hence, the results can be considered as reliable to assess the irritating potential of the test substance to the skin in vitro.
The mean relative tissue viability obtained after 60 minutes treatment with the test item and 42 h post-incubation compared to the negative control tissues was 100.9% (NSMTT-corrected). Since the mean relative tissue viability for the test item was above 50% the test item is considered to be non-irritant. It is concluded that this test is valid and that Bis[4-(tert-butyl)benzoato-O]hydroxyaluminium is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report and should not be classified according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations. - Executive summary:
In the present study the skin irritant potential of Bis[4-(tert-butyl)benzoato-O]hydroxyaluminium was analysed. The EpiDerm™-Standard Model (EPI-200™), a reconstituted three-dimensional human epidermis model, was used as a replacement for the Draize Skin Irritation Test (OECD TG 404) to distinguish between UN GHS “Category 2” skin irritating test substances and not categorized test substances (“No Category”) which may be considered as non-irritant. Hereby, the test item was applied topically. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT after a 60 min exposure and 42 h post-incubation period and compared to those of the concurrent negative controls.
The mixture of 25 mg test item per 1 mL MTT medium showed reduction of MTT compared to the solvent. The mixture turned blue/purple.
For quantitative correction of results, two killed tissues were treated with 25 mg of the test item (KT) and two killed tissues were left untreated as a control (KU), respectively. NSMTT was calculated relative to the negative control of living tissues (NK) according to the following formula:
NSMTT [%] = [(ODKT- ODKU)/ODNK] * 100 = -0.1%
Mean ODKT= 0.051
Mean ODKU= 0.053
Mean ODNK= 1.777
NSMTT was ≤30% (-0.1%) relative to the negative control of living epidermis, the true MTT metabolic conversion (TODTT) of the test item treated living tissues TM was therefore corrected according to the following formula:
TODTT= ODTM– (ODKT– ODKU) = 100.8% - (-0.1%) = 100.9%
The mixture of 25 mg of the test item per 300 µl aqua dest. and per 300 µL isopropanol showed colouring detectable by unaided eye-assessment. Therefore, the absorption of the chemical in water and isopropanol was measured in the range of 570 ± 30 nm.
The test item in isopropanol absorbed light in the relevant range. For quantitative correction of results, the non-specific colour of additional viable tissues (NSCliving) was determined by using additional viable tissues without MTT-staining and calculated according to the following formula:
NSCliving[%] = [ODTVT/ODNK]*100 = 0.5%
Mean ODTVT= 0.008
NSClivingwas ≤ 5% relative to the negative control of living epidermis, therefore no correction of the results was necessary.
As correction with the NSClivingcontrol was not necessary, correction with the NSCkilledcontrol was also not required.
The test item showed no irritant effects. The mean relative tissue viability (% negative control) was > 50% (100.9%, NSMTT-corrected) after 60 min treatment and 42 h post-incubation.
In conclusion the test item showed no irritant effects under the given conditions. The relative mean tissue viability after 60 min of exposure and 42 h post-incubation was > 50%. The test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.
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