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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
Endpoint summary
Administrative data
Description of key information
Weight of evidence: In a subacute oral toxicity study in GFI rats, no toxic effects were observed at 200 mg/kg bw/d, in a subchronic oral toxicity study in mice no toxic effects were observed at 620 mg/kg bw/d, and in a subchronic oral toxicity study in minipigs, no toxic effects were observed at 250 mg/kg bw. Based on the available information, the NOAEL of the test item is greater than 200 mg/kg bw/d (worst case), since no treatment related adverse effects were observed at the highest dose tested.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1976.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- only one dose tested, analytical verification of doses not reported.
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: GIF
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Initial weight: 200-280g - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data.
- Duration of treatment / exposure:
- 50 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 animals (m/f).
- Control animals:
- yes, concurrent no treatment
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Not specified
DETAILED CLINICAL OBSERVATIONS: Not specified
BODY WEIGHT: Yes
- Time schedule for examinations: weekly.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): weekly controls.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes (blood counts)
- Time schedule for collection of blood: at 0, 25 and 50 days of treatment.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 10.
CLINICAL CHEMISTRY: Yes
- How many animals: 10.
- Parameters examined: haemoglobin, urea , GPT and GOT
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
- Macroscopical and microscopical examinations of spleen, kidney, heart, liver, lung and bladder were performed on all animals. - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Details on results:
- Treatment of white rats with diosmin in a dosage of 200 mg/kg daily in diet for 50 days led to no toxic manifestations.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 200 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Conclusions:
- Under test conditions the test item was found to be non toxic, with a NOAEL ≥ 200 mg/kg bw.
- Executive summary:
A study on the subacute oral toxicity of the test item in rats was performed with a procedure similar to OECD 407 (no GLP). White GIF-strain rats received the test item at a dose of 200 mg/kg bw test item in their diet per day for 50 days, and the following parameters were examined: weight development, blood count, macroscopic and histologic assessment of organs, and biochemistry (GOT, GPT, urea). Under test conditions, the test substance showed no toxic effects. Therefore, the NOAEL of the test item in rats is ≥ 200 mg/kg bw.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1976.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- only 2 doses tested
- GLP compliance:
- no
- Limit test:
- no
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Initial weight: 28-33g
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 196 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 60 mg/kg bw/day (nominal)
- Dose / conc.:
- 620 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- Positive control:
- No data.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Not specified
DETAILED CLINICAL OBSERVATIONS: Not specified
BODY WEIGHT: Yes
- Time schedule for examinations: weekly.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): weekly controls.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg
body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain dat
a: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted aver
ages from the consumption and body weight gain data: Not specified
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes (blood counts)
- Time schedule for collection of blood: at 0, 25 and 50 days of treatment.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 10.
CLINICAL CHEMISTRY: Yes
- How many animals: 10.
- Parameters examined: haemoglobin, urea , GPT and GOT
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
- Macroscopical and microscopical examinations of spleen, kidney, heart, liver, lung and bladder were performed on all animals. - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Details on results:
- Treatment of mice with diosmin in a dosage of 60 and 620 mg/kg daily in diet for 196 days led to no toxic manifestations.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 620 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed.
- Key result
- Critical effects observed:
- no
- Conclusions:
- Under test conditions diosmin was found to be non toxic.
- Executive summary:
A study on the subchronic oral toxicity of the test item in mice was performed with a procedure similar to OECD 408 (no GLP). 11 white ICR mice of either sex per dose group received the test item doses of 60 or 620 mg/kg bw test item per day in their diets for 196 days, and the following parameters were examined: weight development, blood count, macroscopic and histologic assessment of organs, and biochemistry (GOT, GPT, urea). Under test conditions, the test substance showed no toxic effects. Therefore, the NOAEL of the test item in mice is ≥ 620 mg/kg bw.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1976.
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)
- Deviations:
- yes
- Remarks:
- only 2 doses tested, treatment for 180 days.
- GLP compliance:
- no
- Limit test:
- no
- Species:
- miniature swine
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Pharmaceutical Institute of the University of Siena, courtesy of Prof. G. Segre. - Route of administration:
- oral: feed
- Vehicle:
- other: milk
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: a suspension in milk of the test item was administered to the animals.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data.
- Duration of treatment / exposure:
- 180 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- No data.
- Control animals:
- yes, concurrent no treatment
- Positive control:
- No data.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Not specified
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Not specified
FOOD EFFICIENCY: Not specified
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: blood count after 0, 45, 90 and 180 days of treatment.
CLINICAL CHEMISTRY: Yes
- Parameters examined: haemoglobin, glucose, urea , uric acid, GOT, GPT, serum lability after Kunkel and Mac Lagan and alkaline phosphatase.
URINALYSIS: Yes
- Parameters examined: density, pH, glucose, haemoglobin, protein, bilirubin, ketones and sediment.
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- Organs examined: Stomach, liver, intestine, lung, heart , kidney, spleen, thyroid gland, adrenal glands, ovaries and testes, brain, duodenum, small intestine, lymph nodes, epididymus, uterus and peripheral nerves.
HISTOPATHOLOGY: Yes
- Organs examined: Stomach, liver, intestine, lung, heart , kidney, spleen, thyroid gland, adrenal glands, ovaries and testes. - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Details on results:
- Treatment of male and female minipigs with diosmin in a dosage of 50 and 250 mg./kg daily in diet for 180 days led to no toxic manifestations. No systematic deviations of clinical, biochemical or hematological values pointing to a toxicological effect of the substance were found.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 250 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Conclusions:
- Under test conditions diosmin was found to be non toxic, with a NOAEL > 250 mg/kg bw.
- Executive summary:
A study on the subacute oral toxicity of the test item in minipigs was performed with a procedure similar to OECD 409 (no GLP). Male and female minipigs received the test item at doses of 50 or 250 mg/kg bw test item per day for 180 days, and the following parameters were observed: weight, blood count at 0, 45, 90, of treatment, blood chemistry (hemoglobin, glucose, uric acid, GOT, GPT, serum lability after Kunkel and Mac Lagan and alkaline phosphatase; urianaysis: density, pH, glucose, hemoglobin, protein, bilirubin, ketones and sediment. After dissection, the following organs were examined macroscopically and histologically: stomach, liver, intestine, lung, heart, kidney, spleen, thyroid gland, adrenal glands, ovaries and testes, whereas the other organs were only examined macroscopically: brain, duodenum, small intestine, lymph nodes, epididymus, uterus and peripheral nerves. No systemic deviations of clinical, biochemical or hematological values pointing to a toxicological effect of the substance were found. Therefore, the NOAEL of the test item in minipigs is ≥ 250 mg/kg bw.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- All studies have a Klimisch score of 2.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Weight of evidence:
- A study on the subacute oral toxicity of the test item in rats was performed with a procedure similar to OECD 407 (no GLP). White GIF-strain rats received the test item at a dose of 200 mg/kg bw test item in their diet per day for 50 days, and the test substance showed no toxic effects. Therefore, the NOAEL of the test item in rats is ≥ 200 mg/kg bw.
- A study on the subchronic oral toxicity of the test item in mice was performed with a procedure similar to OECD 408 (no GLP). 11 white ICR mice of either sex per dose group received the test item doses of 60 or 620 mg/kg bw test item per day in their diets for 196 days, and the following parameters were examined: weight development, blood count, macroscopic and histologic assessment of organs, and biochemistry (GOT, GPT, urea). Under test conditions, the test substance showed no toxic effects. Therefore, the NOAEL of the test item in mice is ≥ 620 mg/kg bw.
- A study on the subacute oral toxicity of the test item in minipigs was performed with a procedure similar to OECD 409 (no GLP). Male and female minipigs received the test item at doses of 50 or 250 mg/kg bw test item per day for 180 days, and the following parameters were observed: weight, blood count at 0, 45, 90, of treatment, blood chemistry (hemoglobin, glucose, uric acid, GOT, GPT, serum lability after Kunkel and Mac Lagan and alkaline phosphatase; urianalysis: density, pH, glucose, hemoglobin, protein, bilirubin, ketones and sediment. After dissection, the following organs were examined macroscopically and histologically: stomach, liver, intestine, lung, heart, kidney, spleen, thyroid gland, adrenal glands, ovaries and testes, whereas the other organs were only examined macroscopically: brain, duodenum, small intestine, lymph nodes, epididymus, uterus and peripheral nerves. No systemic deviations of clinical, biochemical or hematological values pointing to a toxicological effect of the substance were found. Therefore, the NOAEL of the test item in minipigs is ≥ 250 mg/kg bw.
Based on the available information, the NOAEL of the test item is greater than 200 mg/kg bw, since no treatment related adverse effects were observed at the highest dose tested.
Justification for classification or non-classification
Based on the available data, the substance is not classified as STOT RE according to CLP Regulation (EC) No. 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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