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Diss Factsheets
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EC number: 206-019-2 | CAS number: 288-32-4
- 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
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Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guidance Document No. 28 for the conduct of skin absorption studies, March 2004
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- BASF SE Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany
Test material
- Reference substance name:
- Imidazole
- EC Number:
- 206-019-2
- EC Name:
- Imidazole
- Cas Number:
- 288-32-4
- Molecular formula:
- C3H4N2
- IUPAC Name:
- 1H-imidazole
- Details on test material:
- - Name of test material: 14C-Imidazol
- Storage condition of test material: freezer
- Name of test material: Imidazol
- Storage condition of test material: ambient(RT)
- Physical state: white, solid
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 2-C14
Test animals
- Species:
- other: in vitro
Administration / exposure
- Vehicle:
- water
- Duration of exposure:
- 8 hours
- Doses:
- - Nominal doses: 100 and 1000 µg/cm²
- Actual doses: (mean ± SD) 99 ± 3 and 930 ± 18 µg/cm² - Details on study design:
- NUMBER OF DIFFUSION CELLS:
- 8 cells for each dose
DOSE PREPARATION
- A respective aliquot of the radiolabeled test substance was taken and the organic solvent (ethanol) was evaporated. An adequate amount of the non-labeled test substance and tap water was added to the dried residue. The preparations were stirred in order to guarantee homogeneity.
APPLICATION OF DOSE:
- Single topical application. The test-substance preparation was distributed uniformly on the exposed skin preparation using a displacement pipette.
- Amount(s) applied: about 10 μL / cm²
- Actual doses calculated as follows: The exact amount applied per diffusion cell was determined by reweighing the pipette after application, the weight of which had been previously determined after filling.
- Concentration: 10 and 100 mg/mL
- Exposure period: 8 hours
TEST SITE
- Area of exposure: 1 cm²
SAMPLE COLLECTION FOR PENETRATION RATE
- Aliquots of the receptor medium were automatically sampled by the fraction collector 1, 2, 4, 6, 8, 12, and 24 hours after application
SAMPLE COLLECTION FOR MASS BALANCE
- After several washings and the skin surface had dried, the stratum corneum was removed by tape stripping. Scotch Crystal Clear Tape 600 (Art. No: 11265, 3M, France) Six tape strips were taken. The tapes were pooled into two samples for analysis: the first sample containing the first and second tape and the second samplecontaining the third until sixth tape. The remaining skin was analyzed separately.
TEST SAMPLE STORAGE
- Until analysis the samples were stored at room temperature and extracted, likewise at room temperature, using mechanical agitation and/or ultrasonic treatments.
TEST SAMPLE ANALYSIS
- Weighed aliquots of each native receptor fluid sample or of the solvents used for extraction of the diffusion cell parts were analyzed by liquid scintillation counting (Wallac type 1409 or Perkin Elmer Tri-Carb 2800TR). After addition of scintillation cocktail (Hionic Fluor, Perkin Elmer) the samples were counted for 10 min in a LSC and the disintegration rate was determined.
- The recovery of the test substance applied in the various compartments was determined as non-absorbed fraction (donor chamber, dislodgeable test substance, charcoal filter, fraction present in the tape strips), fraction in the remaining skin preparation and absorbed fraction (contents of the receptor chamber, receptor chamber washing and samples taken). - Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: Surgically removed skin from abdomen (BIOPREDIC International, Saint-Grégoire, France and Across Barriers GmbH, Science Park 1, Saabrücken, Germany)
- Type of skin: Dermatomed human skin preparations
- Preparative technique: skin preparation was hydrated in physiological saline for about 10 minutes before mounting to the diffusion cells
- Thickness of skin (in mm): 0.299 – 0.419
- Membrane integrity check: Only visually intact skin with a TEER (impedance value) above 1 kOhm and a TEWL below 15 g/m2h were used.
- Storage conditions: Maximum storage time of 3 days in a refrigerator or 12 months at - 20°C.
PRINCIPLES OF ASSAY
- Diffusion cell: Modified Franz cell (Laboratory Glass Apparatus Inc, U.S.A. or BASF SE) consisting of an upper donor chamber and a wide opening at the top and a lower receptor chamber
- Receptor fluid: tap water for the high and low dose
- Solubility of test substance in receptor fluid: The maximum solubility of the test substance in water is 633 g/L.
- Static system: yes
- Test temperature: 32 ± 1°C
- Occlusion: The openings of the donor chambers were covered with a charcoal filter and Fixomull® Stretch adhesive fleece (semi-occlusive conditions)
Results and discussion
- Signs and symptoms of toxicity:
- not examined
- Dermal irritation:
- not examined
- Absorption in different matrices:
- Dose group: 930 μg/cm² (mean amount of test substance [μg] and (mean % of applied dose))
- Total non-absorbed dose: 56.19 µg (6.04%)
- Absorbed: Sum receptor samples 0 - 24 h including wash out: 568.05 μg (61.06%)
- Absorbed: Receptor fluid: 264.41 μg (28.43%)
- Absorbed: Receptor chamber washing: 24.09 μg (2.59%)
- Absorbed: Total absorbed: 856.55 μg (92.09%)
- Total dose associated to skin: 10.65 µg (1.15%)
- The mean absorption rate of all cells corresponding to the steepest slope of the cumulative absorbed dose curve over time was 255.3 μg/(cm²×h). Taking the applied concentration into account, this is equivalent to a permeability constant of 258.6E-5 cm/h. Furthermore the evaluation of the cumulative absorption curves indicated a mean lag time of about 1.07 hours. The cumulative absorbed dose found in the receptor fluid after the 24-hour exposure period was 92.6% of the applied dose.
Dose group: 99 μg/cm² (mean amount of test substance [μg] and (mean % of applied dose))
- Total non-absorbed dose: 23.38 µg (23.59%)
- Absorbed: Sum receptor samples 0 - 24 h including wash out: 38.54 μg (38.94%)
- Absorbed: Receptor fluid: 26.38 μg (26.61%)
- Absorbed: Receptor chamber washing: 2.09 μg (2.11 %)
- Absorbed: Total absorbed: 67.00 μg (67.66 %)
- Total dose associated to skin: 1.98 µg (2.00%)
- The mean absorption rate of all cells corresponding to the steepest slope of the cumulative absorbed dose curve over time was 14.0 μg/cm²×h. Taking into account the applied concentration, this is equivalent to a permeability constant of 142.4E-5 cm/h. Furthermore the evaluation of the cumulative absorption curves indicated a mean lag time of about 1.37 hours. The cumulative absorbed dose found in the receptor fluid after the 24-hour exposure period was 66.2% of the applied dose. - Total recovery:
- Dose group: 930 μg/cm²
- The mean total recovery measured in diffusion cells equipped with human skin at the high dose fulfilled the OECD quality criteria. The individual values ranged between 96.17 and 100.62 %
Dose group: 99 μg/cm²
- The mean total recovery measured in diffusion cells equipped with human skin at the low dose fulfilled the OECD quality criteria. The individual values ranged between 90.19 and 97.22 %.
Percutaneous absorptionopen allclose all
- Dose:
- 930 μg/cm²
- Parameter:
- percentage
- Absorption:
- 92.09 %
- Remarks on result:
- other: 24 hours
- Remarks:
- 8 hour exposure
- Dose:
- 99 μg/cm²
- Parameter:
- percentage
- Absorption:
- 67.66 %
- Remarks on result:
- other: 24 hours
- Remarks:
- 8 hour exposure
Applicant's summary and conclusion
- Conclusions:
- Under the test conditions OECD 428 and GLP, the mean absorbed doses were 92.09 and 67.66 % of dose for skin treated with about 1000 μg/cm² and 100 μg/cm², respectively. Mean absorption lag times were 1.07 hours and 1.37 hours for the high and low dose, respectively and demonstrate the presence of a functional barrier in the skin samples used.
- Executive summary:
According to OECD guideline 428 and GLP, the diffusion of 14C-Imidazol into and through human skin was assessed by single topical application. Target doses of 1000μg/cm² and 100μg/cm² were applied to split thickness skin preparations mounted on Franz-type diffusion cells. After the exposure time of 8 h and after the sampling period (24 hours after exposure), skin membranes were washed with a mild soap solution and tap water. At the end of the sampling period the test substance was recovered from all compartments of each diffusion cell. The mean total recoveries fulfill the quality criteria put forward in the test guidelines. The mean absorbed doses were 92.09 and 67.66% of dose for skin treated with the high dose and the low dose, respectively. For all dose groups, minor amounts of the test substance were associated with the skin after the exposure period. These amounts accounted to 1.15 and 2.00 % of dose for the high dose and the low dose, respectively. Mean absorption lag times were 1.07 hours and 1.37 hours for the high and low dose, respectively, and demonstrate the presence of a functional barrier in the skin samples used
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