Diosmin

Repeated dose toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1977

Report date:

1976

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

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

Test animals

Species:

rat

Strain:

other: GIF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Initial weight: 200-280g

Administration / exposure

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

Doses / concentrations

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

Examinations

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.

Results and discussion

Results of examinations

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.

Effect levels

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

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

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.