Safety evaluation of certain food additives - ipcs inchem

152 PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS
8.1% phytosterol esters in the diet, equal to phytosterols at a dose of 3.9 g/kg bw
per day, the highest dose tested.
In a 90-day study of toxicity, rats were given phytosterols isolated from soya
beans and esterified with fatty acids from olive oil at a dose of 0, 1, 3 or 9 g/kg bw
per day by gavage. Reduced body weight gain was observed in both sexes, and an
increased incidence of cardiomyopathy was observed in males but not in females
at the highest dose. Slight, reversible changes in haematological parameters
occurred at the two highest doses and were not considered to be adverse effects.
The LOAEL was 9 g/kg bw per day on the basis of effects observed at the highest
dose. The NOAEL for phytosterols was 3 g/kg bw per day.
4.1.2 Short-term studies of toxicity with mixtures of phytosterols and phytostanols
Ninety-day studies of toxicity were available for two mixtures of phytosterols
and phytostanols, which differed slightly in composition owing to different production
processes (solvent extraction, vacuum distillation). In the first study, rats were fed
a phytosterol/phytostanol mixture obtained by solvent extraction at a dietary
concentration of 0, 1.25, 2.5 or 5%, equal to mean intakes of 0, 1.0, 2.0 and
4.2 g/kg bw per day for males and 0, 1.2, 2.4 and 4.8 g/kg bw per day for females
over the study period. No clearly treatment-related effects were seen in this study
at any dose, and the NOEL was 4.2 g/kg bw per day for this mixture of phytosterols
and phytostanols.
The second study was carried out with a phytosterol/phytostanol mixture
obtained by vacuum distillation. Rats were fed the mixture at a dietary concentration
of 0, 1.25, 2.5 or 5%, equal to mean intakes of test material of 0, 0.99, 2.0 and
4.1 g/kg bw per day for males and 0, 1.1, 2.2 and 4.6 g/kg bw per day for females
over the study period. No consistent treatment-related effects were observed, apart
from some changes in clinical chemistry parameters in females, but not in males
(increased activity of serum alanine aminotransferase and -glutamyl transferase
and increased concentrations of urea). Although these observations may indicate
early effects in the liver, no histopathological changes were observed in the liver.
The NOEL was 4.1 g/kg bw per day.
4.1.3 Short-term studies of toxicity with phytostanol ester mixtures
In a 90-day study of toxicity, rats were given one of two mixtures of
phytostanol esters of similar composition, which were derived from wood and from
vegetable oil, respectively. Rats received feed containing the wood-derived mixture
at a concentration of 0, 0.34, 1.7 or 8.4% (w/w) or the vegetable oil–derived mixture
at a concentration of 0, 0.36, 1.8 or 8.9% (w/w), which correspond to the same levels
of phytostanols in the feed. Mean intakes of phytostanols from both mixtures were
0, 0.1, 0.5 and 2.7 g/kg bw per day for males and 0, 0.1, 0.6 and 3.0 g/kg bw per
day for females over the study period. The most prominent treatment-related
findings for both mixtures were decreases in plasma concentrations of vitamins E,
D and K1 in both sexes at the highest dose (about 8.5% phytostanol esters in the
diet). Plasma concentrations of vitamin A and -carotene were unaffected at all
dietary concentrations. The influence of phytosterols and phytostanols on