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EC number: 915-623-1 | 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
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 June 2014 - 26 September 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Version / remarks:
- 13 April 2004
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guidance Document 28: Guidance Document For the Conduct of Skin Absorption Studies
- Version / remarks:
- 5 March 2004
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EFSA Panel on Plant Protection Products and their Residues (PPR); Guidance on Dermal Absorption
- Version / remarks:
- EFSA Journal 2012; 10(4):2665
- Deviations:
- yes
- Remarks:
- according to the EFSA guidance, if standard deviations are > 25% of mean, the preferred approach should be adding the standard deviations to the mean values
- GLP compliance:
- yes
Test material
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- RADIOLABELLING INFORMATION (if applicable)
Radiolabelled isomer 1: 2-(1,1-Dimethylpropyl)[carbonyls-14C]anthraquinone
- Radiochemical purity: 99.2%
- Specific activity: 59 mCi/mmol (211 μCi/mg), 2.18 GBq/mmol (7.78 MBq/mg)
- Locations of the label: carbonyl group
Radiolabelled isomer 2: 2-(1,2-Dimethylpropyl)[carbonyls-14C]anthraquinone
- Radiochemical purity: 99.7%
- Specific activity: 59 mCi/mmol (211 μCi/mg), 2.18 GBq/mmol (7.78 MBq/mg)
- Locations of the label: carbonyl group
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: radiolabelled samples: c.a. -20°C, cold sample: room temperature
- Solubility and stability of the test substance in the solvent/vehicle: soluble in diisobutyl carbinol (DIBC) and Caromax 20LN
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
The test compound was applied to the skin at two concentrations, the solid pure substance as a mixture of the 2 isomers and formulation of the substance containing a mixture of the 2 isomers.
For the solid substance 498.4 mg of non-radiolabelled 2-amylanthraquinone (provided as a mixture of the of the 2 isomers) was added to 1.05 mg of [14C]-2-(1,2-dimethylpropyl)anthraquinone and 1.16 mg of [14C]-2-(1,1-dimethylpropyl)anthraquinone. The mixture was dissolved in acetonitrile and the solvent evaporated off to provide a solid racemic mixture at the desired specific activity. Following radiodilution the test compound was stored in a freezer at ca. 20ºC until the day of application to skin.
For the formulation 747.2 mg of non-radiolabelled 2-amylanthraquinone (provided as a mixture of the of the 2 isomers) was added to 1.32 mg of [14C]-2-(1,2-dimethylpropyl)anthraquinone and 1.76 mg of [14C]-2-(1,1-dimethylpropyl)anthraquinone. The mixture was dissolved in acetonitrile and the solvent evaporated off to provide a solid racemic mixture at the desired specific activity. Following radiodilution the test compound was stored in a freezer at ca. 20ºC until the day of application to skin. On the day of application to skin a 500.22 mg aliquot of the radiodiluted material was dissolved in 0.5044 g of Diisobutyl carbinol (DIBC) followed by 1.0024 g of Caromax 20LN. - Radiolabelling:
- yes
Test animals
- Species:
- other: in vitro human skin from 4 donors
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- other: mixture of Diisobutyl carbinol (DIBC) and Caromax 20LN (0.5:1 w/w)
- Duration of exposure:
- 6 hours, with 24 hours sampling period
- Doses:
- - Actual doses: 4 mg solid substance with 10 µL water added to mimic sweat, or 15 µL formulation, applied to 1.77 cm2 exposed skin
- Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: Dermatomed human skin (359 - 540 μm, obtained from Biopredic International)
- Type of skin: dermatomed
- Preparative technique: not specified
- Thickness of skin (in mm): 359 - 540 μm
- Membrane integrity check: yes
The skin was checked for physical damage prior to being mounted in the test system. The total weight of the cell was recorded, the receptor chamber filled with receptor fluid (((0.9% saline + 5% Bovine serum albumin (BSA) + 5% 2-hydroxypropyl-β-cyclodextrin in water (w/w/w/v)) and the weight recorded again. The system was allowed to warm to approximately 32 ± 2°C prior to application of 50 μL tritiated water (10.3 μCi/mL) onto the skin of each cell. Aliquots (2 x 50 μL) were removed from the receptor fluid chamber for analysis at 0, 0.5, 1 and 2 hours after application and replaced with an equal volume of receptor fluid. Each 50 μL aliquot was mixed with 2 mL Ultima Gold XR® (Perkin Elmer) scintillant, counted on a liquid scintillation counter and the rate of penetration determined from the counts. After the last sampling time the tritiated water was desorbed by rinsing with 0.9% saline. The skin was maintained for use by filling the receptor chamber with receptor fluid and the temperature generally kept at 32 ± 2°C. The skin sample was deemed acceptable if the rate of penetration through the sample was not greater than 2 μL/cm2/h.
PRINCIPLES OF ASSAY
- Diffusion cell: no
- Receptor fluid: 0.9% saline + 5% Bovine serum albumin (BSA) + 5% 2-hydroxypropyl-β-cyclodextrin in water (w/w/w/v)
- Solubility of test substance in receptor fluid: yes
Prior to conducting the main in vitro dermal penetration experiment the solubility of 2-amylanthraquinone in selected receptor fluids was assessed. The receptor fluids were spiked with [14C]-2-amylanthraquinone at a target concentration of 0.2 mg/mL and aliquots taken for liquid scintillation counting to determine the concentration.
- Static system: yes, Franz cells with a nominal 12 ml receptor chamber volume and 1.77 cm2 exposed skin area for dosing
- Flow-through system: no
- Test temperature: Receptor fluid temperature was recorded at each sampling time point and the temperature was maintained at 31.1 – 31.9°C
- Occlusion: no
- Reference substance: yes, radiolabelled testosterone at ca. 0.1 mg/cm2
Samples were taken from the receptor fluid at 8 sampling points over a 24 hour period:
0, 0.5, 1, 2, 4, 6 (taken prior to removal of the dose formulation), 8 and 24 hours after application.
Duplicate aliquots (2 x 50 μl) were removed for sampling and replaced with an equal volume of receptor fluid (0.9% saline + 5% Bovine serum albumin (BSA) + 5% 2-hydroxypropyl-β-cyclodextrin in water w/w/w/v).
Results and discussion
- Absorption in different matrices:
- - Cell wash: mean 0.58% (SD = 0.73) (solid), 26.52** (SD = 8.70) (formulation)
**The atypically high recovery of radioactivity in the cell wash is believed to be formulation/radiolabelled material remaining in the upper portion of the Franz cell (donor chamber). As the concentrations of radioactivity in the receptor fluid were low it is unlikely this is absorbed material.
- Skin wash: mean 95.66% (SD = 1.98) (solid), 18.73% (SD = 6.50) (formulation)
- Skin test site: mean 0.01% (SD 0.2) (solid), 3.35% (SD 5.12) (formulation)
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): mean: below or near the limit of detection (< 0.01%) (solid), 0.14% (SD = 0.07) (formulation)
- Stratum corneum (in vitro test system): (tape strips 3-20): solid: 0.57%, formulation: 37.33% (both values calculated according to the EFSA guidance by adding the standard deviations to mean values in case SD is ≥ 25% of mean)) - Total recovery:
- - Total recovery: mean 97.40% (SD = 1.78) (solid), 96.17% (SD = 2.32) (formulation)
- Recovery of applied dose acceptable: yes, above 95%
- Results adjusted for incomplete recovery of the applied dose: not applicable
- Quantification of values below LOD or LOQ: radioactivity with less than twice background counts were considered to be below the limit of accurate quantification.
Percutaneous absorptionopen allclose all
- Key result
- Time point:
- 24 h
- Dose:
- Solid substance
- Parameter:
- percentage
- Remarks:
- potentially absorbed (receptor fluid, skin, stratum corneum (strips 3-20)
- Absorption:
- 0.25 %
- Remarks on result:
- other:
- Remarks:
- As reported in the study report
- Key result
- Time point:
- 24 h
- Dose:
- 33.2% in formulation (calculated value)
- Parameter:
- percentage
- Remarks:
- potentially absorbed (receptor fluid, skin, stratum corneum (strips 3-20)
- Absorption:
- 24.82 %
- Remarks on result:
- other:
- Remarks:
- As reported in the study report
- Key result
- Time point:
- 24 h
- Dose:
- Solid substance
- Parameter:
- percentage
- Remarks:
- Potentially absorbed (receptor fluid, skin, stratum corneum (tape strips 3-20))
- Absorption:
- 1 %
- Remarks on result:
- other:
- Remarks:
- calculated according to the EFSA guidance, by adding standard deviations to mean values in case SD is ≥ 25% of mean and rounding the value up to one significant figure.
- Key result
- Time point:
- 24 h
- Dose:
- 33.2% in formulation (calculated value)
- Parameter:
- percentage
- Remarks:
- potentially absorbed (receptor fluid, skin, stratum corneum (tapes 3-20)
- Absorption:
- 51 %
- Remarks on result:
- other:
- Remarks:
- calculated according to the EFSA guidance, by adding standard deviations to mean values in case SD is ≥ 25% of mean, and rounding the value to two significant figures.
Any other information on results incl. tables
The solubility of [14C]-2-amylanthraquinone in the selected receptor fluid 0.9% saline + 5% Bovine serum albumin (BSA) + 5% 2-hydroxypropyl-β-cyclodextrin in water (w/w/w/v) was determined. The percentage variation in concentration before and after centrifugation was less than or equal to 7.1% and therefore the solubility of [14C]-2-amylanthraquinone in the receptor fluid was considered acceptable.
To determine the skin preparation integrity tritiated water was applied to the test vessels as described in section 2.3.2. Skin samples were deemed viable if the rate of penetration was not greater than 2 μL/cm2/h. The observed rate of penetration was in the range of 0.460 to 1.82 μL/cm2/h.
During this study the reference standard ([14C]-testosterone) produced a mean penetration rate of 0.0187 μg/cm2/h. Radioactivity recovered was greater than 97%. These results indicate the test system was functional throughout the duration of the study.
Applicant's summary and conclusion
- Conclusions:
- Dermal absoprtion of 2-amylanthraquinone in the form of a solid substance and a 33.2% formulation was studied in an in vitro dermal absorption test. The potentially absorbed amounts were calculated to be 1% and 51% for a solid substance and a formulation, respectively.
- Executive summary:
In a GLP-compliant OECD Guideline 428 study, dermal penetration of 2 -amylanthraquinone was studied in an in vitro dermal absorption test using dermatomized human skin from 4 volunteers. The substance was applied undiluted (with 10 µL water added to mimic sweat), or as a formulation in a mixture of Diisobutyl carbinol (DIBC) and Caromax 20LN (0.5:1 w/w) (calculated concentration 33.2% w/w). The experiment was conducted in Franz cells, representing a static cell design, with a nominal 12 mL receptor chamber volume and 1.77 cm2 exposed skin area for dosing, with each skin sample tested in duplicate. Integrity of the human skin used in each test vessel was demonstrated to be suitable. Functionality of the test system was demonstrated with a reference compound. After 6 hours exposure the skin was washed, and dermal penetration was determined after 24 hours sampling time. Skin fractionation was performed by tape stripping. The total radioactivity recovery was above 95% in both experiments. The potentially absorbed doses (based on the radioactivity in the receptor fluid, skin and stratum corneum (tapes 3 -20)) were reported to be 0.25% for the solid substance and 24.82% for the formulation. However, as standard deviations in most cases exceeded the 25% of the mean values, the dermal absorption values were recalculated by adding standard deviations to the mean values in accordance with the EFSA Guidance on dermal absorption (2012). This resulted in the potentially absorbed doses of 0.6% for the solid substance and 51.35% for the formulation, which were rounded up to 1 and 2 significant figures, respectively, in accordance with the EFSA Guidance on dermal absorption (2012). This resulted in dermal absoprtion values of 1% for pure substance and 51% for the formulation.
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