Hesperidin

Endpoint summary

Description of key information

Overall, following analysis of an extensive range of data in the open peer reviewed literature we conclude that the metabolism of the structurally related, naturally occurring flavonoids, flavanones, flavones and dihydrochalcone glycosides results in significant hydrolysis of the glycosides yielding the corresponding aglycones. These aglycones are readily absorbed, metabolised, conjugated and excreted via the bile and urine, and partly undergo flavone ring cleavage and subsequently cleavage of the three carbon-bridge of dihydrochalcones by the gut flora. A series of polar metabolites are formed that are excreted directly in the feces or absorbed and excreted via the bile and urine, either as such or as their conjugates. 
It is concluded that the toxicokinetic profiles of these six flavonoids follows a common pattern and are considered to be very similar. The use of methyl hesperidin, glucosyl hesperidin, naringin, diosmin and neohesperidin dihydrochalcone as structural surrogates for hesperidin for toxicity and ecotoxicity studies is therefore a valid and justified approach. The flavonone hesperidin is readily absorbed orally and dermally and subsequently metabolized and excreted. No indications for bioaccumulation were noted. A detailed toxicokinetic assessment is attached.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Additional information

An assessment of the Absorption, Distribution, Metabolism, and Excretion of "hesperidin and related flavonoids" was performed to the extent that can be derived from the relevant available information according to the requirements of Annex VIII of the Regulation (EC) 1907/2006. From the analysis of an extensive range of data in the open peer reviewed literature, it was demonstrated that parent flavonoids were not well absorbed. However the ingestion of the flavanones, flavones and dihydrochalcone glycosides (parent flavonoids) can result in significant hydrolysis of the glycosides, yielding the corresponding aglycones. These aglycones are readily absorbed, metabolised, conjugated and excreted via the bile and urine, and partly undergo flavone ring cleavage and subsequently cleavage of the three carbon-bridge of dihydrochalcones by the gut flora. A series of polar metabolites are formed that are excreted directly in the feces or absorbed and excreted via the bile and urine, either as such or as their conjugates. It is concluded that the toxicokinetic profile of these six flavonoids follows a common pattern and is considered to be very similar. The use of methyl hesperidin, glucosyl hesperidin, naringin, diosmin and neohesperidin dihydrochalcone as structural surrogates for hesperidin for toxicity and ecotoxicity studies is therefore a valid and well justified approach.