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

In a standard developmental toxicity study, a mixture of vegetable oil-deri ved stanol fatty acid esters was administered in the diet to groups of 28 m ated 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 equival ent caloric content of fatty acids at each of the treatment levels. The tre atment period extended from day 0 to 21 of gestation. No compound-related t oxicity or clinical effects were seen in any of the treated groups. No stat istically significant differences were seen in body weights or body weight gain in the low or mid-dose groups, although slight but statistically signi ficant decreases in mean body weight relative to controls were seen at gest ation 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 throu ghout the study except for a statistically significant decrease seen only i n the 0- to 7-day gestation period in the high-dose group. No significant e ffects were seen on food consumption in terms of g/rat/day, but a slight, s tatistically significant increase was seen in the mid-dose group during ges tation days 7-14. A significant increase was seen in the high-dose group du ring the 7- to 21-day period of gestation. Reproductive performance was not affected by the treatment. There were no statistically significant differe nces in uterine weight, placental weight, fetal weight, number of fetuses, number of implantation sites, number of corpora lutea, and early/late resor ptions between the treated and control groups. In addition, there was no bi ologically meaningful effect on fetal sex ratio. Visceral and skeletal exam inations did not show any significant increases in the incidence of malform ations, anomalies, or variations that were considered to be treatment relat ed. Dietary plant (8.76% plant stanol esters) stanol esters at concentratio ns up to 5% total stanols were concluded to have no adverse effects on repr oduction or development. (C) 1999 Academic Press.