Developmental toxicity study of vegetable oil-derived stanol fatty acid esters

In a standard developmental toxicity study, a mixture of vegetable oil-derived stanol fatty acid esters was administered in the diet to groups of 28 mated female HsdCpb:WU Wistar rats at concentrations that provided 0, 1, 2.5, and 5% total stanols (equivalent to 0, 1.75, 4.38, and 8.76% plant stanol esters). Test diets were adjusted with rapeseed oil to maintain an equivalent caloric content of fatty acids at each of the treatment levels. The treatment period extended from day 0 to 21 of gestation. No compound-related toxicity or clinical effects were seen in any of the treated groups. No statistically significant differences were seen in body weights or body weight gain in the low- or mid-dose groups, although slight but statistically significant decreases in mean body weight relative to controls were seen at gestation days 7 and 14 in the high-dose group. The decreases in body weight in the high-dose group may be attributable to the virtual lack of absorption of the dietary stanols. Body weight gains were equivalent to controls throughout the study except for a statistically significant decrease seen only in the 0- to 7-day gestation period in the high-dose group. No significant effects were seen on food consumption in terms of g/rat/day, but a slight, statistically significant increase was seen in the mid-dose group during gestation days 7-14. A significant increase was seen in the high-dose group during the 7- to 21-day period of gestation. Reproductive performance was not affected by the treatment. There were no statistically significant differences in uterine weight, placental weight, fetal weight, number of fetuses, number of implantation sites, number of corpora lutea, and early/late resorptions between the treated and control groups. In addition, there was no biologically meaningful effect on fetal sex ratio. Visceral and skeletal examinations did not show any significant increases in the incidence of malformations, anomalies, or variations that were considered to be treatment related. Dietary plant (8.76% plant stanol esters) stanol esters at concentrations up to 5% total stanols were concluded to have no adverse effects on reproduction or development.