Ninety-day toxicity and single-dose toxicokinetics study of alpha-glycosyl isoquercitrin in Sprague-Dawley rats.
alpha-Glycosyl isoquercitrin (AGIQ) is highly absorbable and has been shown to possess antioxidative properties. Based on a favorable safety profile, it has been confirmed as generally recognized as safe (GRAS) compound by the FDA. Nevertheless, safety and toxicity information for AGIQ is still sparse. Therefore, the aim of this study was to test the safety and toxicokinetics of AGIQ in a 90-day study in 60 male and 60 female Sprague-Dawley rats at dietary doses up to 5%. All animals survived until scheduled euthanasia with no clinical signs of toxicity in any animal. AGIQ was rapidly absorbed with metabolism to quercetin and quercetin glucuronide at all dose levels. Statistically significant changes were noted in some tissue weights and clinical chemistry analytes, without evidence of systemic toxicity. The most prominent finding was systemic dose dependent yellow discoloration of bones of treated animals. However, no changes were observed microscopically, and this observation was concluded as toxicologically insignificant. The overall lack of adverse clinical signs, changes in body weight, feed consumption, clinical pathology parameters, and histopathological endpoints in animals administered AGIQ supports no observable adverse effect levels (NOAEL) of 5.0% in diet for both male and female rats (3461 mg/kg/day and 3867 mg/kg/day, respectively).
Sackler School of Medicine, Tel Aviv University, Toxicologic Pathology, Timrat, Israel. Electronic address: anyska@bezeqint.net.
Abraham
A
Nyska
Global Scientific and Regulatory Affairs, San-Ei Gen, F.F.I., Inc., Osaka, Japan.
Shim-Mo
SM
Hayashi
Global Scientific and Regulatory Affairs, San-Ei Gen, F.F.I., Inc., Osaka, Japan.
Mihoko
M
Koyanagi
Integrated Laboratory Systems, Research Triangle Park, NC, USA.
Jeffrey P
JP
Davis
Integrated Laboratory Systems, Research Triangle Park, NC, USA.
Micheal P
MP
Jokinen
Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Yuval
Y
Ramot
Maronpot Consulting LLC, Raleigh, NC, USA.
Robert R
RR
Maronpot
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006027:Glycosides / Q000737:chemistry / Q000633:toxicity*; D006403:Hematologic Tests; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D066007:Toxicokinetics
D006027:Glycosides; C016527:isoquercitrin; D011794:Quercetin
AGIQ; Alpha-glycosyl isoquercitrin; EMIQ; Flavonol; Isoquercitrin; Quercetin; Safety; Sprague-Dawley; Toxicity; Toxicokinetics