Safety evaluation of phytosterol esters. Part 2. Subchronic 90-day oral toxicity study on phytosterol esters--a novel functional food.

Phytosterol esters (PE) are intended for use as a novel food ingredient, primarily in margarines and spreads as a functional component with plasma cholesterol lowering activity. Phytosterols and their esters are present naturally in vegetable oils and on average people consume 200 mg/day, but their consumption at this level is not sufficient to lower plasma cholesterol levels. Therefore, through the incorporation of PE into margarines/spreads, the intake can be increased by approximately 10-fold by consuming the PE-containing margarine/spread at normal intake levels. As part of an extensive programme of safety evaluation studies a subchronic rat toxicity study has been conducted in which groups of Alpk:AP(f)SD (Wistar derived) rats (20 males and 20 females/group) were fed diets containing PE at levels of 0, 0.16, 1.6, 3.2 and 8.1% (w/w) in the diet for 90 days. Throughout the study, clinical observations, body weights, and food and water consumption were measured. At the end of the study the rats were subjected to a full post-mortem examination, cardiac blood samples were taken for clinical pathology, selected organs were weighed, and a full tissue list was taken for subsequent histological examination. There were no treatment-related changes that were considered to be of toxicological significance. Therefore, a nominal PE concentration of 8.1% was considered to be the no-observed-adverse- effect level (NOAEL) following daily oral administration to rats for 90 days. This was equivalent to a dose of 6.6 g/kg body weight/day PE or 4.1 g/kg/day phytosterol.