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EC number: 208-289-7 | CAS number: 520-27-4
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1957
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 957
- Report date:
- 1957
- Reference Type:
- review article or handbook
- Title:
- Absorption, metabolism, and bioavailability of flavonoids
- Author:
- Hollman PCH, Katan MB
- Year:
- 1 998
- Bibliographic source:
- Flavonoids in Health and Disease (Rice-Evans CA and Paker L eds) pp 483–522, Marcel Dekker, Inc., New York
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Method described previously by Booth [Booth AN, Murray CW, Jones FT, DeEds F, 1956. J. Biol. Chem., 223: 251, see 'attached background material']: Breakdown products were identified after diosmin was ingested by rats, using ascending two-dimensional paper chromatograms of the ether extracts of acid urines which were developed with bottom phase of a mixture of chloroform, acetic acid, and water (2:1L1) in the first direction, followed by 20 per cent aqueous potassium chloride in the second direction.
- GLP compliance:
- no
Test material
- Reference substance name:
- Diosmin
- EC Number:
- 208-289-7
- EC Name:
- Diosmin
- Cas Number:
- 520-27-4
- Molecular formula:
- C28H32O15
- IUPAC Name:
- diosmin
- Test material form:
- not specified
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: obtained from Dr. R.M. Horowitz, Pasadena Laboratory, Agricultural Research Service. Obtained by isolation from lemon peel. Before use, these compounds were again crystallized, if necessary, until found to be chromatographically homogeneous in the two-dimensional TLC system used. - Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Diet: purified diet consisting of starch, Cerelose, casein, Cellu flour, salts’ (including potassium acetate and magnesium oxide), oil, and vitamins.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
Administration by stomach tube of 400 mg of diosmin per rat on a purified diet. - Duration and frequency of treatment / exposure:
- Single dose administration.
Doses / concentrations
- Dose / conc.:
- 400 other: mg/rat
- Remarks:
- approximately 1200 mg/kg bw (estimated).
- No. of animals per sex per dose / concentration:
- no data.
- Control animals:
- no
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (excretion)
- Tissues and body fluids sampled: urine.
- Time and frequency of sampling: urine samples were collected at 0 to 7, 7 to 21, 21 to 31, and 31 to 45 hour intervals.
- Analysis: use of ascending two-dimensional paper chromatograms of the ether extracts of acid urines which were developed with the bottom phase of a mixture of chloroform, acetic acid, and water (2: 1: 1) in the first direction, followed by 20 per cent aqueous potassium chloride in the second direction.
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine.
- Time and frequency of sampling: urine samples were collected at 0 to 7, 7 to 21, 21 to 31, and 31 to 45 hour intervals.
- Method type(s) for identification: TLC.
TREATMENT FOR CLEAVAGE OF CONJUGATES: systematic screening of the ether extracts of urine for conjugates of phenolic acids involved hydrolysis with 20 per cent HCl (usually for 2 hours under a reflux), followed by ether extraction of the hydrolysate and migration in the two-dimensional paper chromatographic system. After the air-dried chromatogram was first examined and all fluorescent and absorbing areas visibleunder ultraviolet light were marked, it was sprayed with diazotized sulfanilic acid to form dyes with the phenolic compounds. A direct comparison could then be made between the chromatograms before and after hydrolysis for the appearance of new areas and the disappearance of other areas. The hydrolysis procedure was also applied to specific areas cut out of unsprayed chromatograms of ether extracts of urine, in which case the phenolic acid or flavonoid released could be specifically associated with the suspected conjugate.
Results and discussion
Main ADME results
- Type:
- metabolism
- Results:
- major metabolite: m-hydroxyphenylpropionic acid; traces of m-coumaric acid and diosmetin.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Diosmin can be absorbed in the gastrointestinal tract.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The major metabolite was m-hydroxyphenylpropionic acid (m-HPPA), and only traces of m-coumaric acid and diosmetin were found on the chromatogram.
Applicant's summary and conclusion
- Conclusions:
- Under test conditions, the test substance can be absorbed in the gastrointestinal tract, and the compounds excreted through urine as m-hydroxyphenylpropionic acid, along with traces of m-coumaric acid and diosmetin.
- Executive summary:
The metabolic fate of six flavonoids (hesperidin, hesperetin, diosmin, diosmetin, eriodictyol, and homoeriodictyol) has been studied after oral ingestion by rats, at a dose of 400 mg/rat (no guideline available, no GLP). Urine samples were collected at 0 to 7, 7 to 21, 21 to 31, and 31 to 45 hour intervals and examined by two-dimensional thin layer chromatography. Under test conditions, the test substance was absorbed in the gastrointestinal tract, and excreted through urine as m-hydroxyphenylpropionic acid, along with traces of m-coumaric acid and diosmetin.
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