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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
Key value for chemical safety assessment
Effects on fertility
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
Weight of evidence. Based on the available information from the analogue salt of diosmin, the substance is deemed to be not teratogenic.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- only one dose tested, no information on analytical verification of concentration.
- GLP compliance:
- no
- Limit test:
- no
- Specific details on test material used for the study:
- - Source: diosmin, sodium salt.
- Species:
- mouse
- Strain:
- ICR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Average initial weight: 29 g. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The sodium salt of diosmin was dissolved in water and given by esophageal tube in a daily dose of 50 mg/kg from the 4th to the 12th post-coital days.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 8 days.
- Frequency of treatment:
- Daily
- Duration of test:
- Up to 20 days after conception (group 2).
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 4 groups (2 controls and 2 dosed) of 11 females each.
- Control animals:
- yes, concurrent no treatment
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 19 (group 1)
- Sacrifice (group 2): On the 0, 6, 13 or 20th day after birth the mother animals and offspring were sacrificed.
- Organs examined: in the offspring the following organs were macroscopically and histologically examined: heart, liver, spleen and kidneys. In the mother animals the right and left uterine horns were examined with respect to sites of implantation and absorption. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes. Sex, weight and length were determined.
- Soft tissue examinations: The foetuses were examined with respect to palatal clefts and malformations of the extremities and tail.
- Skeletal examinations: Yes. The skeletons were examined, in particular with respect to vertebral block or cleft formation, number, length, possible fusions and ossifications, form and number of bones.
- Head examinations: No data
- In another group, delivery was by spontaneous birth. The foetuses were macroscopically examined with respect to palatal clefts and malformations of extremities and the tail. Sex, weight and lenght of the foetuses were determined. The development of the animals was followed (openning of the eyes, growth of hair, etc.). - Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- 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:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- No maternal toxic effects were observed.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 50 mg/kg bw (total dose)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): The average weight was of 1.4 g in controls and 1.25 g in treated animals . - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Description (incidence and severity):
- The mean number of animals per litter was 12.3 in the control group and 11.5 in the treated group.
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Neither in the control nor in the diosmin group did the inspection of 126 skeletal preparations each show any pathological findings.
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Assessment of the foetuses did not reveal any difference between the two experimental groups and the control.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 50 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: teratogenicity
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- Under test conditions, the test item has no teratogenic effects. The NOAEL for developmental toxicity in mice is ≥ 50mg/kg bw/d.
- Executive summary:
A study was conducted to assess the teratogenicity potential of the sodium salt of diosmin, by a method similar to OECD 414 (no GLP). Two groups of 11 female ICR mice each were orally administered 50 mg/kg bw/d of test item from the 4th to the 12th post-coital days. Two further control groups were run in parallel. In one of the groups, the foetuses were delivered by laparotomy on the 19th day after conception and the sites of implantation and absorption in both horns of the uterus were determined. The foetuses were examined with respect to palatal clefts and malformations of the extremities and tail; the sex weight and length were determined; then, they were killed and their skeletons stained and examined. In the other treated group, delivery was by spontaneous birth and the development of the animals was followed. There was no reduction in number of foetuses, no increase in absorption sites, no significant alteration of rate of malformations, postnatal morbility, weight gain and development or histology of several organs. Thus, it was concluded that the test item does not have any teratogenic effects. The NOAEL for developmental toxicity of the test item in mice is greater than 50 mg/kg bw/d.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- only one concentration, no information of analytical verification of concentrations.
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: SIV
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Average initial weight: 245g. - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The sodium salt of diosmin was dissolved in water and given by esophageal tube in a daily dose of 100 mg/kg from the 4th to the 14th post-coital days.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy. - Duration of treatment / exposure:
- 10 days.
- Frequency of treatment:
- daily
- Duration of test:
- up to the 20th day after birth.
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 4 groups (2 controls and 2 dosed) of 11 females each.
- Control animals:
- yes, concurrent no treatment
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21 (group 1)
- Sacrifice (group 2): On the 0, 6, 13 or 20th day after birth the mother animals and offspring were sacrificed.
- Organs examined: in the offspring the following organs were macroscopically and histologically examined: heart, liver, spleen and kidneys. In the mother animals the right and left uterine horns were examined with respect to sites of implantation and absorption.
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes. Sex, weight and length were determined.
- Soft tissue examinations: The foetuses were examined with respect to palatal clefts and malformations of the extremities and tail.
- Skeletal examinations: Yes. The skeletons were examined, in particular with respect to vertebral block or cleft formation, number, length, possible fusions and ossifications, form and number of bones.
- Head examinations: No data
- In another group, delivery occurred spontaneously. The foetuses were macroscopically examined with respect to palatal clefts and malformations of extremities and the tail. Sex, weight and lenght of the foetuses were determined. The development of the animals was followed (opening of the eyes, growth of hair, etc.). - Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- 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:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- No maternal toxic effects were observed.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 100 mg/kg bw (total dose)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): The average weight was of 3.56 and 3.17 g, respectively. - Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- After laparotomy, the mean number of animals per litter was of 13.9, both in the control and in the diosmin treated group.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- The inspection of 234 and of 277 skeletal preparations, respectively, did not reveal any pathological features.
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Assessment of the foetuses did not reveal any difference between the two experimental groups.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 100 mg/kg bw (total dose)
- Based on:
- act. ingr.
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- Under test conditions, diosmin has no teratogenic effects. The NOAEL for rats is ≥ 100mg/kg.
- Executive summary:
A study was conducted to assess the teratogenicity potential of the sodium salt of diosmin, by a method similar to OECD 414 (no GLP). Two groups of female SIV rats each were orally administered 100 mg/kg bw/d of test item from the 4th to the 14th post-coital days. Two further control groups were run in parallel. In one of the groups, the foetuses were delivered by laparotomy on the 21st day after conception and the sites of implantation and absorption in both horns of the uterus were determined. The foetuses were examined with respect to palatal clefts and malformations of the extremities and tail; the sex weight and length were determined; then, they were killed and their skeletons stained and examined. In the other treated group, delivery was by spontaneous birth and the development of the animals was followed. There was no reduction in number of foetuses, no increase in absorption sites, no significant alteration of rate of malformations, postnatal morbility, weight gain and development or histology of several organs. Thus, it was concluded that the test item does not have any teratogenic effects. The NOAEL for developmental toxicity in rat is greater than 100 mg/kg bw/d.
Referenceopen allclose all
- After laparotomy, the mean number of animals per litter was 12.3 in the control group and 11.5 in the diosmin treated group. The average weight was of 1.4 g. in controls and 1.25g. in diosmin treated animals. Neither in the control nor in the diosmin group did the inspection of 126 skeletal preparations each show any pathological findings.
- After spontaneous delivery, the average number of animals per litter was 11.35 and 11.4 (respectively in the control and diosmin group). Postnatal mortality (20-day period) was of 19 and 26%, respectively. Weight gain, length, development, gross behavior, growth of hair and opening of the eyes were identical in the two groups. Organ weights, macroscopical and histological findings did not differ significantly in the diosmin treated animals from the control ones.
Table 1. Experimental results on mice.
11 mother animals each |
Sites of implantation |
Number of fetuses |
Absorptions |
Malformations |
Underdeveloped |
|
Controls |
152 |
Live |
125 |
17 |
0 |
26 |
Dead |
10 |
|||||
Diosmin |
143 |
Live |
126 |
17 |
0 |
1 |
Dead |
0 |
- After laparotomy, the mean number of animals per litter was 13.9, both in the control group and in the diosmin treated group. The average weight was of 3.56g. in controls and 3.17g. in diosmin treated animals. The inspection of 234 and 277 skeletal preparations, respectively, did not reveal any pathological features. Assessment of the foetuses led to the same conclusion.
- After spontaneous delivery, the average number of animals per litter was 12.9 and 11.6 (respectively in the control and diosmin group). Postnatal mortality (20-day period) was, of 11 and 20%, respectively. Weight gain, length, development, gross behavior, growth of hair and opening of the eyes were identical in the two groups. Organ weights, macroscopical and histological findings did not differ significantly in the diosmin treated animals from the control ones.
Table 1. Experimental results on rats.
11 mother animals each |
Sites of implantation |
Number of fetuses |
Absorptions |
Malformations |
Underdeveloped |
|
Controls |
294 |
Live |
277 |
17 |
0 |
72 |
Dead |
0 |
|||||
Diosmin |
291 |
Live |
234 |
13 |
0 |
120 |
Dead |
44* |
* 3 whole litters died on the 17th and 18th day after conception.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 50 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Both studies have a Klimisch score of 2.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Weight of evidence: Read-across from analogue substance. Heusser and Oswald (1977) performed teratogenic toxicity studies for the analogue substance diosmin, sodium salt, which was administered by gavage to SIV rats and ICR mice, at doses of 100 and 50 mg/kg bw, respectively.
- In a study conducted to assess the teratogenicity potential of the sodium salt of diosmin, by a method similar to OECD 414 (no GLP), two groups of female SIV rats each were orally administered 100 mg/kg bw/d of test item from the 4th to the 14th post-coital days. Two further control groups were run in parallel. In one of the groups, the foetuses were delivered by laparotomy on the 21st day after conception and the sites of implantation and absorption in both horns of the uterus were determined. The foetuses were examined with respect to palatal clefts and malformations of the extremities and tail; the sex weight and length were determined; then, they were killed and their skeletons stained and examined. In the other treated group, delivery was by spontaneous birth and the development of the animals was followed. There was no reduction in number of foetuses, no increase in absorption sites, no significant alteration of rate of malformations, postnatal morbility, weight gain and development or histology of several organs. Thus, it was concluded that the test item does not have any teratogenic effects. The NOAEL for developmental toxicity in rat is greater than 100 mg/kg bw/d.
- In a study conducted to assess the teratogenicity potential of the sodium salt of diosmin, by a method similar to OECD 414 (no GLP), two groups of 11 female ICR mice each were orally administered 50 mg/kg bw/d of test item from the 4th to the 12th post-coital days. Two further control groups were run in parallel. In one of the groups, the foetuses were delivered by laparotomy on the 19th day after conception and the sites of implantation and absorption in both horns of the uterus were determined. The foetuses were examined with respect to palatal clefts and malformations of the extremities and tail; the sex weight and length were determined; then, they were killed and their skeletons stained and examined. In the other treated group, delivery was by spontaneous birth and the development of the animals was followed. There was no reduction in number of foetuses, no increase in absorption sites, no significant alteration of rate of malformations, postnatal morbility, weight gain and development or histology of several organs. Thus, it was concluded that the test item does not have any teratogenic effects. The NOAEL for developmental toxicity of the test item in mice is greater than 50 mg/kg bw/d.
Based on the available information for the read-across approach, the target substance is deemed to be non teratogenic.
Justification for classification or non-classification
Based on the available information, the substance is not classified for toxicity to reproduction in accordance with CLP Regulation (EC) No. 1272/2008.
Additional information
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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