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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1939
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test is not a guideline method nor GLP compliant, but fulfills basically scientific principles.

Data source

Reference
Reference Type:
publication
Title:
EFFECTS OF NARINGIN AND HESPERIDIN ON ALBINO RATS
Author:
ROBERT H. WILSON, and FLOYD DEEDS
Year:
1940
Bibliographic source:
Journal of Food Science Volume 5, Issue 1, pages 89–92
Report date:
1939

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
As the study had been performed in 1939, prior to any guideline being available, no guideline could be followed. However, basic scientific principles were followed incl. negative control (no treatment) and two different concentrations of test substance application.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Hesperidin
EC Number:
208-288-1
EC Name:
Hesperidin
Cas Number:
520-26-3
Molecular formula:
C28H34O15
IUPAC Name:
5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxo-3,4-dihydro-2H-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:
sample used in this study had a yellowish color and decomposes at 251 °C and were supplied by the Los Angeles Labroatory of Fruit and Vegetable Chemistry of the Bureau of Chemistry aof Chemistry and Soils, U.S. Department of Agriculture.

Test animals

Species:
rat
Strain:
other: Albino
Sex:
male
Details on test animals or test system and environmental conditions:
The rats averaging 50 grams body weight were used at the start of the feeding experiment.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
Hesperidin was mixed with the stock diet in concentrations up to one percent by weight. The animals had free access to food and water at all times.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
200 days
Frequency of treatment:
continuous
Doses / concentrationsopen allclose all
Dose / conc.:
0.062 other: percent by body weight
Dose / conc.:
1 other: percent by body weight
No. of animals per sex per dose:
six to eight rats per dose level, sex not specified
Control animals:
yes, concurrent no treatment
Details on study design:
Male albino rats averaging 50 grams body weight at the start of the feeding experiment were used, six to eight rats for each dosage level. The substance was mixed with the stock diet in concentrations up to one percent by weight.The animals had free access to food and water at all times.
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
Observations were made on growth curves, weights of important viscera, and macroscopic and microscopic examination of these tissues.
Sacrifice and pathology:
Histological examination of paraffin sections stained with hematoxylin-eosin
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
During the last 50 days respiratory infection was observed throughout the laboratory colony, not related the test article affecting weight gain in this last period of experiment.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Growth curves of negative controls and dose groups fully parallel.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
only blood sugar values were monitored
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
During the last 50 days respiratory infection was observed throughout the laboratory colony, not related the test article.
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
The weights of the hearts, spleens, livers, adrenals, kidneys and testes were all within normal range and no macroscopical abnormalities were noted. Histopathological examinations showed no significant morphological changes.
Histopathological findings: neoplastic:
not specified
Details on results:
At the end of 200 days all the rats were killed with ether and autopsied. The weights of the hearts, spleens, livers, adrenals. kidneys, and testes were all within the normal range. All organs appeared normal range. All organs appeared normal macroscopically except the lungs of rats having respiratory infection. Histological examination of paraffin sections stained with hematoxylin-eosin showed no significant morphological changes in the livers, hearts, kidneys, spleens, adrenals. and testes of rats receiving hesperidin.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 other: percent by weight in food
Based on:
test mat.
Sex:
male
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
No effects were observed; 1% in diet applied to rats were converted to ca. 750 mg/kg/day calculated for rats with a mean body weight of ca. 250 g and ca. 20 g/day of food consumption.
Dose descriptor:
NOAEL
Effect level:
750 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
No effects were observed; 1% in diet applied to rats were converted to ca. 750 mg/kg/day calculated for rats with a mean body weight of ca. 250 g and ca. 20 g/day of food consumption.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
There was no difference between control rats and those receiving hesperidin in the test, giving a negative result. Thus, the NOAEL can be set to 1% (ca. 750 mg) by weight per day in food in this study.
Executive summary:

The continued feeding to healthy albino rats of hesperidin in a standard diet for a period of 200 days, in concentrations as high as one percent of the diet by weight, gave no evidences of cumulative injury as judged by growth curves, weights of important viscera, and macroscopic and microscopic examination of these tissues. There was no difference between control rats and those receiving hesperidin in the test, giving a negative result. Thus, the NOAEL can be set to 1% (ca. 750 mg) by weight per day in food in this study. This value is consistent with another NOAEL value on Neohesperidin dihydrochalcone (a surrogate to hesperidin) in the study of B.A.R. Lina, et al. (1990) and taking into account that rats of 50 g weight were used at the start of the experiment.