Hesperidin

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

6.4.1989 - 26.4.1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well documented guidline study prior to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diosmine 90% (consists of 90% diosmin, and 10% hesperidin)

IUPAC Name:

Diosmine 90% (consists of 90% diosmin, and 10% hesperidin)

Constituent 2

Reference substance name:

Diosmin

EC Number:

208-289-7

EC Name:

Diosmin

Cas Number:

520-27-4

Molecular formula:

C28H32O15

IUPAC Name:

5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxo-4H-chromen-7-yl 6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

lot No. 23/89
Commercial name Flavonoides 90% Diosmine consisting of 90% diosmin and 10% hesperidin)
Particle size analysis: 5.3% < 1.6 µm, 7.3% < 2.2 µm, 11.5% < 3.0 µm, 29.6% < 5.3 µm; median diameter 8.6 µm

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

A 550 L inhalation chamber was used and test substance concentration, oxygen content and temperature were controlled. Compressed air was used and filtered prior to use for suspension of dust into the chamber. Concentration during exposure was measured as 5.05 ±0.83 g/m3 and median diameter of particles was 8.6 µm. Oxygen concentration was 21% vol and temperature was 25.0-25.3 °C

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.04 g/m3 was used as limit concentration for exposure, measured as 5.05 ±0.83 g/m3

No. of animals per sex per dose:

10 rats were used (5 males and 5 females)

Control animals:

yes

Details on study design:

Exposure time to test atmosphere was 4 hours and 15 minutes. Thereafter, animals were observed for 14 days and body weight was recorded daily prior to necropsy.

Statistics:

no data

Results and discussion

Preliminary study:

No mortality was observed, neither in the group of animals exposed to 5.04 g/m3 diosmin nor in the control group. Weight gain of animals during 14 day observation period was normal and did not show abnormalities.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC0

Effect level:

> 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC0

Effect level:

> 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 4

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no mortality was observed throughout the experiment

Clinical signs:

other: clinical signs during exposure and observation period were normal (equivalent in test group and control group)

Body weight:

body weigth gain was normal for all animals used in the test.

Gross pathology:

no macroscopic abnormalities were noted following autopsy of the test animals following the experiment

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a limit test for acute inhalative toxicity to rats using whole body dust exposure no mortality was observed at 5.04 g/m3 and no clinical signs were noted. Following the experiment no macroscopical abnormalities were noted during autopsy. Thus the substance is considered practically nontoxic by inhalative exposire to rats.

Executive summary:

The tested Flanoides 90% diosmine contains 90% diosmin, a structurally very similar substance to hesperidin and 10% hesperidin.

During the investigation for acute inhalative toxicity to rats following dust exposure no mortality and no clinical signs were noted in any of the animals following exposure to the limit concentration of 5.04 g/m3, exposed to for 4 hours. In addition autopsy did not reveal any abnormalities in the test group in any organs. Thus the tested material is considered practically nontoxic and it can be reasonably assumed that neither diosmin nor hesperidin poses any risk by inhalative exposure to rats.