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.