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EC number: 236-216-9 | CAS number: 13241-33-3
- 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
- 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:
- 2 016
- Report date:
- 2016
Materials and methods
- Objective of study:
- absorption
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Neohesperidin was determined by UHPLC-MS/MS in rat plasma after a single administration of Poncirus trifoliata extract to 6 rats.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- (S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one
- EC Number:
- 236-216-9
- EC Name:
- (S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one
- Cas Number:
- 13241-33-3
- Molecular formula:
- C28H34O15
- IUPAC Name:
- (S)-7-[[2-O-6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl]oxy]-2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: The powdered P. trifoliata fruits (100 g) were extracted by refluxing with water (1 : 15, w/v) for 2 h.2 The aqueous extract was filtered, concentrated under reduced pressure by using a rotary evaporation apparatus, and lyophilized to give a powder (15.6 g). The powder was suspended in 0.5% CMC–Na solution to get a concentration equivalent to 0.156 g/ml of P. trifoliata extract.
- Purity: Neohesperidin, NE: 0.604 mg/mL.
- Hesperidin, HE: 1.61 mg/mL
- Hesperidin Methyl chalcone, HMC: 0.378 mg/mL.
- Poncirin, PO: 2.06 mg/mL.
- Phellopterin, PH: 0.196 mg/mL. - Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Laboratory Animal Center of China Medical University (Shenyang, China).
- Weight at study initiation: 230 ± 20 g
ENVIRONMENTAL CONDITIONS
- All animals were kept in conformity with the European Community guidelines for the use of experimental animals (86/609/EEC).
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- other: 0.5% CMC–Na solution
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: lyophylized p. trifoliata extract was suspended in 0.5% CMC–Na solution to get a concentration equivalent to 0.156 g/mL of extract (0.604 mg/mL neohesperidin).
- Duration and frequency of treatment / exposure:
- single dose.
Doses / concentrations
- Dose / conc.:
- 6.04 mg/kg bw/day (nominal)
- Remarks:
- Neohesperidin in plant extract. Dose of P. trifoliata extract of 1.56 g/kg (equivalent to 16.1, 6.04, 3.78, 20.6, and 1.96 mg/kg of HE, NE, HMC, PO, and PH, respectively).
- No. of animals per sex per dose / concentration:
- 6 males
- Control animals:
- no
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, plasma.
- Time and frequency of sampling: Serial blood samples (approximately 0.3 mL) were collected through the oculi chorioideae vein in heparinized tubes at 0, 5, 15, and 30 min, and then at 1, 1.5, 2, 3, 5, 8, 12, and 24 h.
- Other: Plasma was separated by centrifugation (2500 x g, 10 min), and stored at -20 ºC until analysis.
ANALYTICAL METHOD:
- Separation method: UHPLC. UHPLC system (Dionex UltiMate 3000) with a cooling autosampler and column oven and a TSQ Quantum Ultra mass spectrometer (Thermo Scientific, San Jose, USA) with an electrospray ionization (ESI) interface.
- Conditions: Agilent XDB C18 column (100 x 2.1 mm and 1.8 mm). The mobile phase consisted of water containing 0.1% formic acid (solvent A) and acetonitrile (solvent B). The gradient elution program
was set as follows: 20 / 45% B (v/v) at 0–5.0 min; 45 / 90% B at 5.0–5.5 min, 90% B at 5.5–6.5 min; 90 / 20% B at 6.5–7.0 min; 20% B at 7.0–10.0 min. The flow rate was set at 0.35 mL/min and injection volume was 2 mL using a partial loop mode for sample injection. The temperatures of the column and autosampler were maintained at 30 and 10ºC, respectively.
- Detection method: MS/MS. Mass spectrometric detection was performed using an ESI source via polarity switching between positive and negative (for NE) ionization mode; m/z 609.2 / 301.0 was used as quantifier for NE.
- Limits of detection and quantification: LOQ = 2.0 ng/ml for NE.
- Extraction recovery (indicate if results are corrected or not for recoveries): 88.4 - 93.9%. Results not corrected.
- Validation: Method validation was performed according to the guidelines set by the United States Food and Drug Administration (FDA) for bioanalytical method validation. Linear range for NE was 2.0 - 250 ng/ml, r = 0.9962, accuracy 99.5%, RSD = 2.5%.
Results and discussion
Main ADME results
- Type:
- absorption
- Results:
- quick absorption, detection in plasma 5 min after oral administration.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- These compounds were quickly absorbed into the body and were detected 5 min after oral administration.
Toxicokinetic parametersopen allclose all
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- Tmax: 1.18 ± 0.57 h
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- Cmax: 19.1 ± 3.6 ng/mL
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 4.17 ± 1.04 h
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: 79.2 μg/(L·h)
- Remarks:
- to the last measurable concentration
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: 94.8 μg/(L·h)
- Remarks:
- to infinity
Metabolite characterisation studies
- Metabolites identified:
- not measured
Applicant's summary and conclusion
- Conclusions:
- The substance was quickly absorbed and found in plasma 5 minutes after oral administration, reaching a maximum plasma concentration of 19.1 ± 3.6 ng/mL, the half-life of elimination (T1/2) was 4.17 ± 1.04 h.
- Executive summary:
A pharmacokinetic study was performed after a single oral administration of Poncirus trifoliata extract to 6 male Sprague-Dawley rats, containing 0.604 mg/mL of neohesperidin, which resulted in a dose of 6.04 mg/kg bw of neohesperidin. Neohesperidin content was determined in rat plasma by means of a validated UHPLC-MS/MS method. The substance was quickly absorbed and found in plasma 5 minutes after oral administration. The relevant toxicokinetic parameters obtained were the following: The time of maximum plasma concentration (Tmax) and maximum plasma concentration (Cmax) were 1.18 ± 0.57 h and 19.1 ± 3.6 ng/mL, the half-life of elimination (T1/2) was 4.17 ± 1.04 h, and the area under the curve to the last measurable concentration (AUC0–t) and to infinity (AUC) were 79.2 and 94.8 mg/Lh.
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