Basic toxicology and metabolism studies of 1,5-anhydro-D-fructose using bacteria, cultured mammalian cells, and rodents.
1,5-Anhydro-D-fructose (AF) is a monosaccharide occurring in edible morels, red seaweeds and certain mammalian tissues. It can be formed directly from starch and glycogen in vivo by alpha-1,4-glucan lyase (EC 4.2.2.13). In this study, the toxicity, absorption and metabolism of AF using bacteria, mammalian cells, rat and mouse models were examined. In Ames test, AF showed no genotoxicity using five strains of the bacterium Salmonella typhimurium TA 98, 100, 102, 1535 and 1537. AF caused no mammalian gene mutation as tested with mouse lymphoma L5178Y cells. AF did not cause toxic symptoms in rats when it was administered as a single oral dose of 5 g/kg and observed over a 14-day period. Furthermore, at necropsy, no signs of abnormality were detected. Daily intraperitoneal (ip) administration of 2 g/kg AF to mice did not induce adverse effects throughout a 28-day period. Radioactive tracing experiments using 14C-labeled AF indicated that AF was efficiently absorbed since the major portion of radioactive material was recovered in urine. Further work using unlabeled AF indicated that the cyclic polyol 1,5-anhydro-D-sorbitol (AS) increased dramatically in both blood and urine upon AF administration at 1 g/kg ip, suggesting the existence of an efficient reduction mechanism from AF to AS, which was then excreted in urine. In conclusion, these studies indicate that AF had low or no toxicity and showed no mutagenicity.
Yu
Shukun
S
Danisco Innovation, Danisco A/S, Copenhagen, Denmark. g7sy@danisco.com
Mei
Jie
J
Ahrén
Bo
B
D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D009153:Mutagens; D005632:Fructose; C048927:1,5-anhydrofructose