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EC number: 208-288-1 | CAS number: 520-26-3
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1982-1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: performed scientifically, detailed information, fulfill basic principles
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- In vivo exposure to plant flavonols: Influence on frequencies of micronuclei in mouse erythrocytes and sister-chromatid exchange in rabbit lymphocytes
- Author:
- James T. MacGregor et al
- Year:
- 1 983
- Bibliographic source:
- Mutation Research/Genetic Toxicology Volume 124, Issues 3–4, December 1983, Pages 255–270
- Report date:
- 1983
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- hesperetin dihydrochalcone (HDHC)
- IUPAC Name:
- hesperetin dihydrochalcone (HDHC)
- Reference substance name:
- 35400-60-3
- Cas Number:
- 35400-60-3
- IUPAC Name:
- 35400-60-3
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Hesperetin dihydrochalcone (HDHC) was synthesized from hesperidin and was subsequently recrystallized from ethanol/water. The purity of HDHC was indicated to be at least 95%.
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- Swiss Webster
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Males or female Swiss-Webster mice with group mean weights at time of initial dosing of 16-32 g (approximately 6 weeks of age) were obtained from Simonsen Laboratories, Gilroy, CA. Animals were age-matched within each experiment.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- acacia (gum arabic)
- Details on exposure:
- oral dosing of NHDC and HDHC was by gavage in 2% acacia(gum arabic) in water at 10ml/kg.bw. Control animals received acacia by the same route and in the same solvent volume at test animals.
- Duration of treatment / exposure:
- 6h and 30h
- Frequency of treatment:
- continuous
- Post exposure period:
- no data
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
Basis:
actual ingested
NHDC: 5000, 1000, 500, 500(repeat), 200mg/kg
- Remarks:
- Doses / Concentrations:
Basis:
actual ingested
HDHC:1000, 300, 100mg/kg
- No. of animals per sex per dose:
- 6 mice/dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- triethylenemelamine(TEM)
Examinations
- Tissues and cell types examined:
- bone marrow, polychromatic and normochromatic erythrocytes
- Details of tissue and slide preparation:
- Bone marrow was sampled 6 h after the second of 2 doses given 24 h apart( for NHDC). Bone marrow from both femurs was suspended in fetal bovine serum and smears were made. Slides were air-dried, fixed in absolute methanol, and stained with filtered Wright-Giemasa stain.
The incidence of micronuclei in polychromatic and normochromatic erythrocytes, and the ratio of polychromatic to normochromatic erythrocytes, were scored at 1000× under oil immersion by an observer who was unaware of the identity of the randomized and coded slides. The polychromatic/ normochromatic erythrocyte was based on a minimum of 500 erythrocytes.
Bone marrow was sampled at various times following a single dose of test agent. Sample preparation and scoring were as described above. Positive control animals were sacrificed at 48 h after treatment, but were dosed at varying times to correspond with actual sampling of animals treated with test compounds.
Micronucleus frequencies in peripheral blood erythrocytes were monitored following a single dose of test agent. Peripheral blood was obtained by pricking the ventral tail vessels with a 25 G needle, then transferring the blood with a 10µl capillary tube to a slide containing 3-5µl of fetal bovine serium. The resulting blood smears were treated, stained and scored in the same manner as the bone marrow smears.
In all cases, group values are micronucleated cells per total cells scored. The percentage of polychromatic erythrocytes was determined by the number of polychromatic cells in the fields containing the first 500 mormochromatic erythrocytes. - Evaluation criteria:
- dosage groups compared with control groups at P<0.05 .
- Statistics:
- micronucleus frequencies in polychromatic erythrocytes of treated groups were compared with concurrent control values using both the negative binomial comparison and the binomial comparison. Micronucleus frequencies in norchromatic erythrocytes were compared with concurrent control values by the binomial comparison.
Values which exceed the critical values for significance at the 5% or 1% levels are indicated.
The negative binomial test was set up to determine whether or not a 3-fold or greater increase over the spontaneous value in all comparable control groups was observed at a type 2()error of 0.10.
The Kruskal-Wallis 1-way analysis of variance by ranks was used to test for differences in the percentage of polychromatic erythrocytes among groups.When the analysis of variance for the concurrent negative control and all dosage groups of a single test agent was significant at P<0.05, subsequent pairwise comparisons were made to determine which individual dosage groups differed from the concurrent control group.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- None of the flavonoids tested gave a reproducible dose-related increase in micronucleus frequency using 2-dose protocol. Although 3 individual test groups exceeded the critical value for 5% significance, this is not unexpected when 36 individual pairwise comparisons with the concurrent control groups are made. Two of these high values were due to a single mouse which received 500 mg/kg NHDC, p.o. This animal had 14 micronucleated cells among 1000 polychromatic erythrocytes(PCE) and 3 micronucleated cells among 245 normorchromatic erythrocytes(NCE). No other animal in this group had a value above 2 micronuclei/1000 PCE or NCE, nor was there evidence of an increased micronucleus frequency in any other dose group in this experiment.
A repeat experiment at 500 mg/kg NHDC failed to show any evidence of and increased micronucleus frequency in any of 6 additional mice. No data is not considered to support a flavonoid-related increase in the micronucleus frequency.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
No consistent increase in the micronucleus frequency were observed in bone marrow or peripheral blood erythrocytes from mice treated with neohesperidin dihydrochalcone and hesperetin dihydrochalcone under various exposure and sampling conditions. As both, neohesperidin dihydrochalcone and hesperetin dihydrochalcone are direct metabolites of hesperidin (see section on toxicokinetics), the results can be considered representative for hesperidin too. - Executive summary:
In vivo micronucleus assay was conducted to determine the mutagenicity potential of test compounds with Swiss-Webster male and female mice. Oral dosing of Neohesperidin dihydrochalcone (NHDC) and Hesperetin dihydrochalcone(HDHC) was by gavage in 2% acacia (gum arabic) in water at 10 ml/kg.bw. Control animals received acacia by the same route and in the same solvent volume at test animals. Bone marrow was sampled 6 h after the second of 2 doses given 24 h apart. The incidence of micronuclei in polychromatic and normochromatic erythrocytes, and the ratio of polychromatic to normochromatic erythrocytes, were scored. Micronucleus frequencies in peripheral blood erythrocytes were monitored following a single dose of test agent. HDHC and NHDC, at p.o. doses of 100 -1000 mg/kg, did not increase the micronucleus frequency in bone marrow erythrocytes 6h after the second of 2 doses 24 apart. These results fail to indicate that clastogenesis in bone marrow erythoblats due to oral administration of the flavonols studies is at most very weak. As both, neohesperidin dihydrochalcone and hesperetin dihydrochalcone are direct metabolites of hesperidin (see section on toxicokinetics), the results can be considered representative for hesperidin too.
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