Sub-chronic (13-week) oral toxicity study, preceded by an in utero exposure phase and genotoxicity studies with fish source phosphatidylserine in rats.
The safety of fish phosphatidylserine (PS) conjugated to DHA (InCog™) was examined in a series of toxicology studies as first step to support future use in infants and general population using in vitro genotoxicity tests and in a sub-chronic toxicity study with an in-utero exposure phase. PS is a major lipid in the cell membrane, active in various membrane-mediated processes. PS-DHA, present in human milk, has been suggested to be important for early brain development. Rats were exposed to diets containing 1.5%, 3% or 4.5% InCog or two control diets. Parental (F0) animals were fed throughout mating, gestation and lactation. Subsequently, a subchronic, 13-week study was conducted on the F1 animals followed by 4 weeks of recovery. The genotoxicity tests showed no mutagenicity potential. No significant toxicological findings were found in the F0 rats or the F1 pups. In the 13-weeks study, an increase in the presence of renal minimal-mild multifocal corticomedullary mineralization was noted in nine females of the high-dose group. This change was not associated with any inflammatory or degenerative changes in the kidneys. The no-observed-adverse-effect level (NOAEL) in the present study was placed at 3% in the diet (mid-dose group), equivalent to an overall intake of at least 2.1 g InCog/kg bw/day in the F1 generation.
Nutrition R&D, Enzymotec, Migdal HaEmeq, Israel. Electronic address: yaell@enzymotec.com.
Y
Y
Lifshitz
Nutrition R&D, Enzymotec, Migdal HaEmeq, Israel.
L
L
Levi
Nutrition R&D, Enzymotec, Migdal HaEmeq, Israel.
I
I
Eyal
Nutrition R&D, Enzymotec, Migdal HaEmeq, Israel.
T
T
Cohen
Nutrition R&D, Enzymotec, Migdal HaEmeq, Israel.
S
S
Tessler
D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000818:Animals; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008297:Male; D018811:Maternal Exposure; D009152:Mutagenicity Tests; D009929:Organ Size; D010718:Phosphatidylserines / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D010718:Phosphatidylserines; D004281:Docosahexaenoic Acids
90-Day sub-chronic toxicity study; DHA; InCog; Infant; Phosphatidylserine; Safety