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EC number: 208-291-8 | CAS number: 520-34-3
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1993.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- GLP compliance:
- no
Test material
- Reference substance name:
- 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone
- EC Number:
- 208-291-8
- EC Name:
- 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone
- Cas Number:
- 520-34-3
- Molecular formula:
- C16H12O6
- IUPAC Name:
- 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-chromen-4-one
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source: Apin Chemicals Ltd., Oxon, UK. - Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: around 200 g
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: arabic gum
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: suspension in arabic gum.
Doses / concentrations
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- po.
- Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- 5-hydroxyflavone (100mg/kg po)
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, blood.
- Time and frequency of sampling: urine was collected for the 24 hr after the treatment using metabolic cages; urine samples were pooled. Blood extracts were obtained from treated rats at various times after gavage. Animals were killed at the various times after treatment and whole blood collected (3-4 ml). All the biological samples were immediately frozen at -20ºC until use.
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: urine was collected for the 24 hr after the treatment using metabolic cages.
- From how many animals: number not specified, urine samples were pooled.
- Method type(s) for identification: HPLC-DAD (Perkin-Elmer, LC250, equipped with a 10 x 0.46 cm column filled with Nucleosil 5CN stationary phase, 5um; MachereyNagel, Düren, Germany), detection at 345 nm. Identification of metabolites was achieved by one and two-dimensional NMR experiments.
TREATMENT FOR CLEAVAGE OF CONJUGATES: Samples to be analyzed were incubated as such in duplicate in a 50 mM sodium phosphate buffer (pH 5.5) in the presence of 1000 units/mI of b-glucuronidase (Sigma) (final volume, 200ul) for 1 hr at 37ºC. Controls were run simultaneously under the same conditions, except for b-glucuronidase, which was replaced by the same volume of buffer. The reactions were stopped by adding 400ul of acetonitrile and centrifuged. Fifty ul of both supematants were injected and analyzed by HPLC.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- No unchanged flavonoid could be detected, while under similar conditions nearly 100% of the aglycone was recovered from control blood spiked with diosmetin. Diosmetin is rapidly metabolized to several glucuronides, probably at the level of the intestinal mucosa. The 2 main metabolites appeared within few minutes of treatment, and plateaued after 2-6h. After 24h, the metabolites were no longer detectable in circulating blood. Treatment with b-glucuronidase of both blood and urine led to the disappearance of all metabolites and to the concomitant appearance of diosmetin.
- Details on excretion:
- In 24h urine samples, the same four metabolites found in blood could be seen, plus an extra peak, present in control urines. Treatment with b-glucuronidase of both blood and urine led to the disappearance of all metabolites and to the concomitant appearance of diosmetin.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- At least 4 metabolites with spectra fitting flavonoid structures, (not present in controls) could be isolated from the blood samples: 4 glucuronides were found, the main two metabolites being diosmetin 3'-glucuronide, and a diosmetin diglucuronide.
Applicant's summary and conclusion
- Conclusions:
- Diosmetin is rapidly metabolized to several glucuronides, probably at the level of the intestinal mucosa, inmmediately after administration. Four metabolites (diosmetin glucuronides) appear in blood within few minutes and plateau at 2-6h, and are eliminated within 24h. The same metabolites can be found in urine after 24h.
- Executive summary:
A study of the metabolic fate of diosmetin after oral administration was performed on male Sprague-Dawley rats, following basic scientific principles (no GLP). Based on the results obtained, it can be stated that diosmetin is rapidly metabolized to several glucuronides, probably at the level of the intestinal mucosa, inmmediately after administration. Four metabolites (diosmetin glucuronides) appear in blood within few minutes and plateau at 2-6h, and are eliminated within 24h. The same metabolites can be found in urine after 24h.
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